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Sample records for cells healing atherosclerotic

  1. Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipoprotein E knockout mice

    DEFF Research Database (Denmark)

    Bentzon, Jacob F; Sondergaard, Claus S; Kassem, Mustafa;

    2007-01-01

    circulating bone marrow-derived progenitor cells. Here, we analyzed the contribution of this mechanism to plaque healing after spontaneous and mechanical plaque disruption in apolipoprotein E knockout (apoE-/-) mice. METHODS AND RESULTS: To determine the origin of SMCs after spontaneous plaque disruption......, irradiated 18-month-old apoE-/- mice were reconstituted with bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic apoE-/- mice and examined when they died up to 9 months later. Plaque hemorrhage, indicating previous plaque disruption, was widely present, but no bone marrow-derived e......GFP+ SMCs were detected. To examine the origin of healing SMCs in a model that recapitulates more features of human plaque rupture and healing, we developed a mechanical technique that produced consistent plaque disruption, superimposed thrombosis, and SMC-mediated plaque healing in apoE-/- mice. Mechanical...

  2. Cell Therapy for Wound Healing

    OpenAIRE

    You, Hi-Jin; Han, Seung-Kyu

    2014-01-01

    In covering wounds, efforts should include utilization of the safest and least invasive methods with goals of achieving optimal functional and cosmetic outcome. The recent development of advanced wound healing technology has triggered the use of cells to improve wound healing conditions. The purpose of this review is to provide information on clinically available cell-based treatment options for healing of acute and chronic wounds. Compared with a variety of conventional methods, such as skin...

  3. Prevalence of Foam Cells and Helper-T cells in Atherosclerotic Plaques of Korean Patients with Carotid Atheroma

    OpenAIRE

    Lee, Won-Ha; Ko, Young-Hyeh; Kim, Dong-Ik; Lee, Byung-Boong; Park, Jeong-Euy

    2000-01-01

    Background Inflammation and activation of immune cells have important roles in the pathogenesis of atherosclerosis. We analyzed the involvement of various immune cells in the pathogenesis of atherosclerosis. Methods We investigated the presence of foam cells, lymphocytes and killer cells in 11 atherosclerotic plaque specimens removed from Korean patients who underwent carotid endoarterectomy. Atherosclerotic plaques were analyzed by immunohistochemistry using monoclonal antibody specific to f...

  4. Protective effects ofMallotus furetianus on functions of endothelial progenitor cells in atherosclerotic rats

    Institute of Scientific and Technical Information of China (English)

    Yue-Li Liu; Dan Zhou; Lian-Bo Lin; Chen Yang

    2015-01-01

    Objective:To investigate protective effects ofMallotus furetianus(M. furetianus)on functions of endothelial progenitor cells (EPCs) in atherosclerotic rats.Methods:Atherosclerosis was established by intraperitoneal injection of vitamin D3 combined with high fat diet for 9 weeks. Extracts ofM. furetianus were given to prevent damage of EPCs in dose of 0.081 g/kg and 0.026 g/kg. Rats were sacrificed, and then mononuclear cells were isolated from bone marrow to culture EPCs and test the functions of EPCs.Results:M. furetianus can improve the capacities of EPCs on proliferation, migration, adhesion, and tubule formation in doses of 0.081 g/kg; improve adhesion, and tubule formation in dose of 0.026 g/kg in atherosclerotic rats. Conclusion:M. furetianus can protect functions of EPCs in atherosclerotic rats.

  5. Stem Cells for Cutaneous Wound Healing

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    Giles T. S. Kirby

    2015-01-01

    Full Text Available Optimum healing of a cutaneous wound involves a well-orchestrated cascade of biological and molecular processes involving cell migration, proliferation, extracellular matrix deposition, and remodelling. When the normal biological process fails for any reason, this healing process can stall resulting in chronic wounds. Wounds are a growing clinical burden on healthcare systems and with an aging population as well as increasing incidences of obesity and diabetes, this problem is set to increase. Cell therapies may be the solution. A range of cell based approaches have begun to cross the rift from bench to bedside and the supporting data suggests that the appropriate administration of stem cells can accelerate wound healing. This review examines the main cell types explored for cutaneous wound healing with a focus on clinical use. The literature overwhelmingly suggests that cell therapies can help to heal cutaneous wounds when used appropriately but we are at risk of clinical use outpacing the evidence. There is a need, now more than ever, for standardised methods of cell characterisation and delivery, as well as randomised clinical trials.

  6. Stem Cells for Cutaneous Wound Healing

    OpenAIRE

    Giles T. S. Kirby; Stuart J. Mills; Cowin, Allison J.; Smith, Louise E.

    2015-01-01

    Optimum healing of a cutaneous wound involves a well-orchestrated cascade of biological and molecular processes involving cell migration, proliferation, extracellular matrix deposition, and remodelling. When the normal biological process fails for any reason, this healing process can stall resulting in chronic wounds. Wounds are a growing clinical burden on healthcare systems and with an aging population as well as increasing incidences of obesity and diabetes, this problem is set to increase...

  7. Mast Cells Regulate Wound Healing in Diabetes.

    Science.gov (United States)

    Tellechea, Ana; Leal, Ermelindo C; Kafanas, Antonios; Auster, Michael E; Kuchibhotla, Sarada; Ostrovsky, Yana; Tecilazich, Francesco; Baltzis, Dimitrios; Zheng, Yongjun; Carvalho, Eugénia; Zabolotny, Janice M; Weng, Zuyi; Petra, Anastasia; Patel, Arti; Panagiotidou, Smaro; Pradhan-Nabzdyk, Leena; Theoharides, Theoharis C; Veves, Aristidis

    2016-07-01

    Diabetic foot ulceration is a severe complication of diabetes that lacks effective treatment. Mast cells (MCs) contribute to wound healing, but their role in diabetes skin complications is poorly understood. Here we show that the number of degranulated MCs is increased in unwounded forearm and foot skin of patients with diabetes and in unwounded dorsal skin of diabetic mice (P diabetic mice. Pretreatment with the MC degranulation inhibitor disodium cromoglycate rescues diabetes-associated wound-healing impairment in mice and shifts macrophages to the regenerative M2 phenotype (P diabetic mice deficient in MCs have delayed wound healing compared with their wild-type (WT) controls, implying that some MC mediator is needed for proper healing. MCs are a major source of vascular endothelial growth factor (VEGF) in mouse skin, but the level of VEGF is reduced in diabetic mouse skin, and its release from human MCs is reduced in hyperglycemic conditions. Topical treatment with the MC trigger substance P does not affect wound healing in MC-deficient mice, but improves it in WT mice. In conclusion, the presence of nondegranulated MCs in unwounded skin is required for proper wound healing, and therapies inhibiting MC degranulation could improve wound healing in diabetes. PMID:27207516

  8. Wound healing of intestinal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Masahiro Iizuka; Shiho Konno

    2011-01-01

    The intestinal epithelial cells (IECs) form a selective permeability barrier separating luminal content from underlying tissues. Upon injury, the intestinal epithelium undergoes a wound healing process. Intestinal wound healing is dependent on the balance of three cellular events;restitution, proliferation, and differentiation of epithelial cells adjacent to the wounded area. Previous studies have shown that various regulatory peptides, including growth factors and cytokines, modulate intestinal epithelial wound healing. Recent studies have revealed that novel factors, which include toll-like receptors (TLRs), regulatory peptides, particular dietary factors, and some gastroprotective agents, also modulate intestinal epithelial wound repair. Among these factors, the activation of TLRs by commensal bacteria is suggested to play an essential role in the maintenance of gut homeostasis. Recent studies suggest that mutations and dysregulation of TLRs could be major contributing factors in the predisposition and perpetuation of inflammatory bowel disease. Additionally, studies have shown that specific signaling pathways are involved in IEC wound repair. In this review, we summarize the function of IECs, the process of intestinal epithelial wound healing, and the functions and mechanisms of the various factors that contribute to gut homeostasis and intestinal epithelial wound healing.

  9. Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes

    DEFF Research Database (Denmark)

    Barascuk, Natasha; Skjøt-Arkil, Helene; Register, Thomas C;

    2010-01-01

    BACKGROUND: Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular......-I in areas of intimal hyperplasia and in shoulder regions of advanced plaques. Treatment of human monocytes with M-CSF or M-CSF+LDL generated macrophages and foam cells producing CTX-I when cultured on type I collagen enriched matrix. Circulating levels of CTX-I were not significantly different in women...... with aortic calcifications compared to those without. CONCLUSIONS: Human macrophage foam cells degrade the atherosclerotic plaques though cathepsin K mediated processes, resulting in increase in levels of CTX-I. Serum CTX-I was not elevated in women with aortic calcification, likely due to the contribution...

  10. Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

    OpenAIRE

    Son, Dong Ju; Kim, Soo Yeon; Han, Seong Su; Kim, Chan Woo; Kumar, Sandeep; Park, Byeoung Soo; Lee, Sung Eun; Yun, Yeo Pyo; Jo, Hanjoong; Park, Young Hyun

    2012-01-01

    Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significant...

  11. Quantifying cell behaviors during embryonic wound healing

    Science.gov (United States)

    Mashburn, David; Ma, Xiaoyan; Crews, Sarah; Lynch, Holley; McCleery, W. Tyler; Hutson, M. Shane

    2011-03-01

    During embryogenesis, internal forces induce motions in cells leading to widespread motion in tissues. We previously developed laser hole-drilling as a consistent, repeatable way to probe such epithelial mechanics. The initial recoil (less than 30s) gives information about physical properties (elasticity, force) of cells surrounding the wound, but the long-term healing process (tens of minutes) shows how cells adjust their behavior in response to stimuli. To study this biofeedback in many cells through time, we developed tools to quantify statistics of individual cells. By combining watershed segmentation with a powerful and efficient user interaction system, we overcome problems that arise in any automatic segmentation from poor image quality. We analyzed cell area, perimeter, aspect ratio, and orientation relative to wound for a wide variety of laser cuts in dorsal closure. We quantified statistics for different regions as well, i.e. cells near to and distant from the wound. Regional differences give a distribution of wound-induced changes, whose spatial localization provides clues into the physical/chemical signals that modulate the wound healing response. Supported by the Human Frontier Science Program (RGP0021/2007 C).

  12. [Stem cells and growth factors in wound healing].

    Science.gov (United States)

    Pikuła, Michał; Langa, Paulina; Kosikowska, Paulina; Trzonkowski, Piotr

    2015-01-01

    Wound healing is a complex process which depends on the presence of various types of cells, growth factors, cytokines and the elements of extracellular matrix. A wound is a portal of entry for numerous pathogens, therefore during the evolution wound healing process has formed very early, being critical for the survival of every individual. Stem cells, which give rise to their early descendants progenitor cells and subsequently differentiated cells, play a specific role in the process of wound healing. Among the most important cells which take part in wound healing the following cells need to be distinguished: epidermal stem cells, dermal precursor of fibroblasts, adipose-derived stem cells as well as bone marrow cells. The activity of these cells is strictly regulated by various growth factors, inter alia epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF). Any disorders in functioning of stem cells and biological activity of growth factors may lead to the defects in wound healing, for instance delayed wound healing or creation of hypertrophic scars. Therefore, knowledge concerning the mechanisms of wound healing is extremely essential from clinical point of view. In this review the current state of the knowledge of the role of stem cells and growth factors in the process of wound healing has been presented. Moreover, some clinical aspects of wound healing as well as the possibility of the therapy based on stem cells and growth factors have included.

  13. Intravital live cell triggered imaging system reveals monocyte patrolling and macrophage migration in atherosclerotic arteries

    Science.gov (United States)

    McArdle, Sara; Chodaczek, Grzegorz; Ray, Nilanjan; Ley, Klaus

    2015-02-01

    Intravital multiphoton imaging of arteries is technically challenging because the artery expands with every heartbeat, causing severe motion artifacts. To study leukocyte activity in atherosclerosis, we developed the intravital live cell triggered imaging system (ILTIS). This system implements cardiac triggered acquisition as well as frame selection and image registration algorithms to produce stable movies of myeloid cell movement in atherosclerotic arteries in live mice. To minimize tissue damage, no mechanical stabilization is used and the artery is allowed to expand freely. ILTIS performs multicolor high frame-rate two-dimensional imaging and full-thickness three-dimensional imaging of beating arteries in live mice. The external carotid artery and its branches (superior thyroid and ascending pharyngeal arteries) were developed as a surgically accessible and reliable model of atherosclerosis. We use ILTIS to demonstrate Cx3cr1GFP monocytes patrolling the lumen of atherosclerotic arteries. Additionally, we developed a new reporter mouse (Apoe-/-Cx3cr1GFP/+Cd11cYFP) to image GFP+ and GFP+YFP+ macrophages "dancing on the spot" and YFP+ macrophages migrating within intimal plaque. ILTIS will be helpful to answer pertinent open questions in the field, including monocyte recruitment and transmigration, macrophage and dendritic cell activity, and motion of other immune cells.

  14. Oleic acid induces smooth muscle foam cell formation and enhances atherosclerotic lesion development via CD36

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    Tang Bing

    2011-04-01

    Full Text Available Abstract Background Elevated plasma free fatty acid (FFA levels have been linked to the development of atherosclerosis. However, how FFA causes atherosclerosis has not been determined. Because fatty acid translocase (FAT/CD36 is responsible for the uptake of FFA, we hypothesized that the atherogenic effects of FFA may be mediated via CD36. Results We tested this hypothesis using cultured rat aortic smooth muscle cells (SMCs treated with oleic acid (OA. We found that OA induces lipid accumulation in SMCs in a dose dependent manner. Rat aortic SMCs treated for 48 hours with OA (250 μmol/L became foam cells based on morphological (Oil Red O staining and biochemical (5 times increase in cellular triglyceride criteria. Moreover, specific inhibition of CD36 by sulfo-N-succinimidyl oleate significantly attenuated OA induced lipid accumulation and foam cell formation. To confirm these results in vivo, we used ApoE-deficient mice fed with normal chow (NC, OA diet, NC plus lipolysis inhibitor acipimox or OA plus acipimox. OA-fed mice showed increased plasma FFA levels and enhanced atherosclerotic lesions in the aortic sinus compared to the NC group (both p 5 μm2 vs. OA plus acipimox: 2.60 ± 0.10 ×105 μm2, p p Conclusions These findings suggest that OA induces smooth muscle foam cell formation and enhances atherosclerotic lesions in part though CD36. Furthermore, these findings provide a novel model for the investigation of atherosclerosis.

  15. Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jing-Hsien [School of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Tsai, Chia-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Wang, Chi-Ping [Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Hui-Hsuan, E-mail: linhh@csmu.edu.tw [Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China)

    2013-10-15

    Gossypetin, a flavone originally isolated from Hibiscus species, has been shown to possess antioxidant, antimicrobial, and antimutagenic activities. Here, we investigated the mechanism(s) underlying the anti-atherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of > 50 μM of gossypetin could scavenge over 50% of DPPH radicals. The inhibitory effects of gossypetin on the lipid and protein oxidation of LDL were defined by thiobarbituric acid reactive substance (TBARS) assay, the relative electrophoretic mobility (REM) of oxidized LDL (ox-LDL), and fragmentation of apoB in the Cu{sup 2+}-induced oxidation of LDL. Gossypetin showed potential in reducing ox-LDL-induced foam cell formation and intracellular lipid accumulation, and uptake ability of macrophages under non-cytotoxic concentrations. Molecular data showed that these influences of gossypetin might be mediated via peroxisome proliferator-activated receptor α (PPARα)/liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) and PPARγ/scavenger receptor CD36 pathways, as demonstrated by the transfection of PPARα siRNA or PPARγ expression vector. Our data implied that gossypetin regulated the PPAR signals, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that gossypetin potentially could be developed as an anti-atherosclerotic agent. - Highlights: • The anti-atherosclerotic effect of gossypetin in vitro was examined. • Gossypetin inhibited LDL oxidation. • Gossypetin showed potential in reducing on the formation of foam cells. • Gossypetin functions against ox-LDL through PPARa activation and PPARγ depression.

  16. Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

    Energy Technology Data Exchange (ETDEWEB)

    Son, Dong Ju [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Kim, Soo Yeon [Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of); Han, Seong Su [University of Iowa Carver College of Medicine, Department of Pathology, Iowa City, IA (United States); Kim, Chan Woo [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Department of Bioinspired Science, Ehwa Womans University, Seoul (Korea, Republic of); Kumar, Sandeep [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Park, Byeoung Soo [Nanotoxtech Co., Ansan (Korea, Republic of); Lee, Sung Eun [Division of Applied Biology and Chemistry, Kyungpook National University, Daegu (Korea, Republic of); Yun, Yeo Pyo [College of Pharmacy, Chungbuk National University, Cheongju (Korea, Republic of); Jo, Hanjoong, E-mail: hjo@emory.edu [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Department of Bioinspired Science, Ehwa Womans University, Seoul (Korea, Republic of); Park, Young Hyun, E-mail: pyh012@sch.ac.kr [Department of Food Science and Nutrition, College of Natural Sciences, Soonchunhyang University, Asan (Korea, Republic of)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.

  17. Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation

    International Nuclear Information System (INIS)

    Gossypetin, a flavone originally isolated from Hibiscus species, has been shown to possess antioxidant, antimicrobial, and antimutagenic activities. Here, we investigated the mechanism(s) underlying the anti-atherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of > 50 μM of gossypetin could scavenge over 50% of DPPH radicals. The inhibitory effects of gossypetin on the lipid and protein oxidation of LDL were defined by thiobarbituric acid reactive substance (TBARS) assay, the relative electrophoretic mobility (REM) of oxidized LDL (ox-LDL), and fragmentation of apoB in the Cu2+-induced oxidation of LDL. Gossypetin showed potential in reducing ox-LDL-induced foam cell formation and intracellular lipid accumulation, and uptake ability of macrophages under non-cytotoxic concentrations. Molecular data showed that these influences of gossypetin might be mediated via peroxisome proliferator-activated receptor α (PPARα)/liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) and PPARγ/scavenger receptor CD36 pathways, as demonstrated by the transfection of PPARα siRNA or PPARγ expression vector. Our data implied that gossypetin regulated the PPAR signals, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that gossypetin potentially could be developed as an anti-atherosclerotic agent. - Highlights: • The anti-atherosclerotic effect of gossypetin in vitro was examined. • Gossypetin inhibited LDL oxidation. • Gossypetin showed potential in reducing on the formation of foam cells. • Gossypetin functions against ox-LDL through PPARa activation and PPARγ depression

  18. Collective cell migration: Implications for wound healing and cancer invasion

    Directory of Open Access Journals (Sweden)

    Li Li

    2013-07-01

    Full Text Available During embryonic morphogenesis, wound repair and cancer invasion, cells often migrate collectively via tight cell-cell junctions, a process named collective migration. During such migration, cells move as coherent groups, large cell sheets, strands or tubes rather than individually. One unexpected finding regarding collective cell migration is that being a "multicellular structure" enables cells to better respond to chemical and physical cues, when compared with isolated cells. This is important because epithelial cells heal wounds via the migration of large sheets of cells with tight intercellular connections. Recent studies have gained some mechanistic insights that will benefit the clinical understanding of wound healing in general. In this review, we will briefly introduce the role of collective cell migration in wound healing, regeneration and cancer invasion and discuss its underlying mechanisms as well as implications for wound healing.

  19. Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets

    NARCIS (Netherlands)

    Jager, Nynke A.; de Vries, Bastiaan M. Wallis; Hillebrands, Jan-Luuk; Harlaar, Niels J.; Tio, Rene A.; Slart, Riemer H. J. A.; van Dam, Gooitzen M.; Boersma, Hendrikus H.; Zeebregts, Clark J.; Westra, Johanna

    2016-01-01

    In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated. Twenty-three consecutive plaques removed during carotid endarter

  20. Effects of Dermal Multipotent Cell Transplantation on Skin Wound Healing

    Institute of Scientific and Technical Information of China (English)

    ShiChunmeng; ChengTianmin; SuYongping; RanXinze; MaiYue; QuJifu; LouShufen; XuHui; LuoChengji

    2005-01-01

    There is increasing evidence that dermis contains adult multipotent stem cells. To investigate the effects of dermis-derived multipotent cells on wound healing, we transplanted a clonal population of dermis-derived multipotent cells (termed as DMCs) by topical and systemic application into the skin wound of rats with simple wounds and rats with combined wound and radiation injury. Our results suggest that both topical and systemic transplantation of DMCs accelerate the healing process in rats with a simple wound; the promoting effect by topical transplantation occurs earlier than systemic transplantation. However, systemic transplantation of DMCs promotes the healing process in irradiated rats, while topical transplantation of DMCs fails. Further studies on the mechanisms of DMCs to promote wound healing indicate that the supernatant of DMCs could promote the proliferation of fibroblasts and epidermal cells; DMCs expressed transcripts of a serics of cytokincs and cxtraccllular matrix molecules, including VEGF, PDGF, HGF, TGF-β, ICAM-1, VCAM-1, and Fibronectin, which were closely related to the wound healing by DNA microarray analysis. The implanted DMCs can engraft into recipient skin wounded tissues after transplantation by the FISH analysis with Y-chromosome-specific probe. Systemic transplantation of DMCs also promotes the recovery of peripheral white blood cells in irradiated rats. These results demonstrate the different effects of DMCs on wound healing in nonirradiated and irradiated rats and illustrate the importance of optimizing wound healing via the topical or systemic transplantation of stem cells.

  1. Low numbers of FOXP3 positive regulatory T cells are present in all developmental stages of human atherosclerotic lesions.

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    Onno J de Boer

    Full Text Available BACKGROUND: T cell mediated inflammation contributes to atherogenesis and the onset of acute cardiovascular disease. Effector T cell functions are under a tight control of a specialized T cell subset, regulatory T cells (Treg. At present, nothing is known about the in situ presence of Treg in human atherosclerotic tissue. In the present study we investigated the frequency of naturally occurring Treg cells in all developmental stages of human atherosclerotic lesions including complicated thrombosed plaques. METHODOLOGY: Normal arteries, early lesions (American Heart Association classification types I, II, and III, fibrosclerotic plaques (types Vb and Vc and 'high risk' plaques (types IV, Va and VI were obtained at surgery and autopsy. Serial sections were immunostained for markers specific for regulatory T cells (FOXP3 and GITR and the frequency of these cells was expressed as a percentage of the total numbers of CD3+ T cells. Results were compared with Treg counts in biopsies of normal and inflammatory skin lesions (psoriasis, spongiotic dermatitis and lichen planus. PRINCIPLE FINDINGS: In normal vessel fragments T cells were virtually absent. Treg were present in the intima during all stages of plaque development (0.5-5%. Also in the adventitia of atherosclerotic vessels Treg were encountered, in similar low amounts. High risk lesions contained significantly increased numbers of Treg compared to early lesions (mean: 3.9 and 1.2%, respectively. The frequency of FOXP3+ cells in high risk lesions was also higher compared to stable lesions (1.7%, but this difference was not significant. The mean numbers of intimal FOXP3 positive cells in atherosclerotic lesions (2.4% was much lower than those in normal (24.3% or inflammatory skin lesions (28%. CONCLUSION: Low frequencies of Treg in all developmental stages of human plaque formation could explain the smoldering chronic inflammatory process that takes place throughout the longstanding course of

  2. Secretome of Peripheral Blood Mononuclear Cells Enhances Wound Healing

    OpenAIRE

    Mildner, Michael; Hacker, Stefan; Haider, Thomas; Gschwandtner, Maria; Werba, Gregor; Barresi, Caterina; Zimmermann, Matthias; Golabi, Bahar; Tschachler, Erwin; Ankersmit, Hendrik Jan

    2013-01-01

    Non-healing skin ulcers are often resistant to most common therapies. Treatment with growth factors has been demonstrated to improve closure of chronic wounds. Here we investigate whether lyophilized culture supernatant of freshly isolated peripheral blood mononuclear cells (PBMC) is able to enhance wound healing. PBMC from healthy human individuals were prepared and cultured for 24 hours. Supernatants were collected, dialyzed and lyophilized (SECPBMC). Six mm punch biopsy wounds were set on ...

  3. Stem Cell-Based Therapeutics to Improve Wound Healing

    OpenAIRE

    Hu, Michael S.; Tripp Leavitt; Samir Malhotra; Dominik Duscher; Pollhammer, Michael S.; Walmsley, Graham G.; Zeshaan N. Maan; Alexander T. M. Cheung; Manfred Schmidt; Georg M. Huemer; Longaker, Michael T.; Peter Lorenz, H.

    2015-01-01

    Issues surrounding wound healing have garnered deep scientific interest as well as booming financial markets invested in novel wound therapies. Much progress has been made in the field, but it is unsurprising to find that recent successes reveal new challenges to be addressed. With regard to wound healing, large tissue deficits, recalcitrant wounds, and pathological scar formation remain but a few of our most pressing challenges. Stem cell-based therapies have been heralded as a promising mea...

  4. Cell-based screening identifies the active ingredients from Traditional Chinese Medicine formula Shixiao San as the inhibitors of atherosclerotic endothelial dysfunction.

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    Xiaofan Wang

    Full Text Available In this study, we performed a phenotypic screening in human endothelial cells exposed to oxidized low density lipoprotein (an in vitro model of atherosclerotic endothelial dysfunction to identify the effective compounds in Shixiao San. After investigating the suitability and reliability of the cell-based screening method using atorvastatin as the positive control drug, this method was applied in screening Shixiao San and its extracts. The treatment of n-butanol fraction on endothelial cells exhibited stronger healing effects against oxidized low density lipoprotein-induced insult when compared with other fractions. Cell viability, the level of nitric oxide, endothelial nitric oxide synthase and endothelin-1 were measured, respectively. The assays revealed n-butanol fraction significantly elevated the survival ratio of impaired cells in culture. In parallel, n-butanol fraction exhibited the highest inhibition of inflammation. The generation of prostaglandin-2 and adhesion molecule (soluble intercellular adhesion molecule-1 was obviously declined. Furthermore, n-butanol fraction suppressed the production of reactive oxygen species and malondialdehyde, and restored the activity of superoxide dismutase. Compounds identification of the n-butanol fraction was carried out by ultra high liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry. The active ingredients including quercetin-3-O-(2G-α-l-rhamnosyl-rutinoside, quercetin-3-O-neohesperidoside, isorhamnetin-3-O-neohesperidoside and isorhamnetin-3-O-rutinoside revealed the ability of anti-atherosclerosis after exposing on endothelial cells. The current work illustrated the pharmacology effect of Shixiao San and clearly indicated the major active components in Shixiao San. More importantly, the proposed cell-based screening method might be particularly suitable for fast evaluating the anti-atherosclerosis efficacy of Traditional Chinese Medicines and screening out the

  5. Mesenchymal stem cells improve medullary inflammation and fibrosis after revascularization of swine atherosclerotic renal artery stenosis.

    Directory of Open Access Journals (Sweden)

    Behzad Ebrahimi

    Full Text Available Atherosclerotic renal artery stenosis (ARAS raises blood pressure and can reduce kidney function. Revascularization of the stenotic renal artery alone does not restore renal medullary structure and function. This study tested the hypothesis that addition of mesenchymal stem cells (MSC to percutaneous transluminal renal angioplasty (PTRA can restore stenotic-kidney medullary tubular transport function and attenuate its remodeling. Twenty-seven swine were divided into three ARAS (high-cholesterol diet and renal artery stenosis and a normal control group. Six weeks after ARAS induction, two groups were treated with PTRA alone or PTRA supplemented with adipose-tissue-derived MSC (10 × 10(6 cells intra-renal. Multi-detector computed tomography and blood-oxygenation-level-dependent (BOLD MRI studies were performed 4 weeks later to assess kidney hemodynamics and function, and tissue collected a few days later for histology and micro-CT imaging. PTRA effectively decreased blood pressure, yet medullary vascular density remained low. Addition of MSC improved medullary vascularization in ARAS+PTRA+MSC and increased angiogenic signaling, including protein expression of vascular endothelial growth-factor, its receptor (FLK-1, and hypoxia-inducible factor-1α. ARAS+PTRA+MSC also showed attenuated inflammation, although oxidative-stress remained elevated. BOLD-MRI indicated that MSC normalized oxygen-dependent tubular response to furosemide (-4.3 ± 0.9, -0.1 ± 0.4, -1.6 ± 0.9 and -3.6 ± 1.0 s(-1 in Normal, ARAS, ARAS+PTRA and ARAS+PTRA+MSC, respectively, p<0.05, which correlated with a decrease in medullary tubular injury score (R(2 = 0.33, p = 0.02. Therefore, adjunctive MSC delivery in addition to PTRA reduces inflammation, fibrogenesis and vascular remodeling, and restores oxygen-dependent tubular function in the stenotic-kidney medulla, although additional interventions might be required to reduce oxidative-stress. This study supports development of

  6. Cell-cycle regulatory proteins in human wound healing

    DEFF Research Database (Denmark)

    Bartkova, Jirina; Grøn, Birgitte; Dabelsteen, Erik;

    2003-01-01

    Proper healing of mucosal wounds requires careful orchestration of epithelial cell migration and proliferation. To elucidate the molecular basis of the lack of cellular proliferation in the migrating 'epithelial tongue' during the re-epithelialization of oral mucosal wounds, the expression of cel...

  7. Pharmacokinetic analysis of the uptake of liposomes by macrophages and foam cells in vitro and their distribution to atherosclerotic lesions in mice.

    Science.gov (United States)

    Chono, Sumio; Tauchi, Yoshihiko; Morimoto, Kazuhiro

    2006-02-01

    In order to evaluate the efficacy of liposomes as a drug carrier for atherosclerotic therapy, a pharmacokinetic analysis of the uptake of liposomes by macrophages and foam cells in vitro and their distribution to atherosclerotic lesions in mice was carried out. In brief, liposomes of three particle sizes (500, 200 and 70 nm) were prepared, and the uptake of liposomes by these cells in vitro and the aortic distribution following intravenous administration to atherogenic mice were examined. The internalization rate constant calculated by measuring uptake and binding was size-dependent in both types of cells in vitro. The aortic clearance (CL(a)) was size-independent in atherogenic mice and the CL(a) of 200 nm particles was the highest. Surprisingly, the aortic distribution in vivo did not correspond with the internalization to macrophages and foam cells in vitro. These results suggest that there is an optimal size for the distribution of liposomes to atherosclerotic lesions.

  8. A polymer scaffold for self-healing perovskite solar cells

    Science.gov (United States)

    Zhao, Yicheng; Wei, Jing; Li, Heng; Yan, Yin; Zhou, Wenke; Yu, Dapeng; Zhao, Qing

    2016-01-01

    Advancing of the lead halide perovskite solar cells towards photovoltaic market demands large-scale devices of high-power conversion efficiency, high reproducibility and stability via low-cost fabrication technology, and in particular resistance to humid environment for long-time operation. Here we achieve uniform perovskite film based on a novel polymer-scaffold architecture via a mild-temperature process. These solar cells exhibit efficiency of up to ~16% with small variation. The unencapsulated devices retain high output for up to 300 h in highly humid environment (70% relative humidity). Moreover, they show strong humidity resistant and self-healing behaviour, recovering rapidly after removing from water vapour. Not only the film can self-heal in this case, but the corresponding devices can present power conversion efficiency recovery after the water vapour is removed. Our work demonstrates the value of cheap, long chain and hygroscopic polymer scaffold in perovskite solar cells towards commercialization.

  9. The Use of Stem Cells in Burn Wound Healing: A Review

    OpenAIRE

    Fadi Ghieh; Rosalyn Jurjus; Amir Ibrahim; Alice Gerges Geagea; Hisham Daouk; Bassel El Baba; Sana Chams; Michel Matar; Wadih Zein; Abdo Jurjus

    2015-01-01

    Burn wound healing involves a series of complex processes which are subject to intensive investigations to improve the outcomes, in particular, the healing time and the quality of the scar. Burn injuries, especially severe ones, are proving to have devastating effects on the affected patients. Stem cells have been recently applied in the field to promote superior healing of the wounds. Not only have stem cells been shown to promote better and faster healing of the burn wounds, but also they h...

  10. Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Kazuki [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Senokuchi, Takafumi; Ishii, Norio; Kinoshita, Hiroyuki; Yamada, Sarie; Murakami, Saiko [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Nakao, Saya [Department of Environmental & Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto (Japan); Motoshima, Hiroyuki; Kondo, Tatsuya; Kukidome, Daisuke; Kawasaki, Shuji [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Kawada, Teruo [Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto (Japan); Nishikawa, Takeshi; Araki, Eiichi [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan)

    2015-01-30

    Highlights: • Statins induce PPARγ activation in vascular smooth muscle cells. • Statin-induced PPARγ activation is mediated by COX-2 expression. • Statins suppress cell migration and proliferation in vascular smooth muscle cells. • Statins inhibit LPS-induced inflammatory responses by PPARγ activation. • Fluvastatin suppress the progression of atherosclerosis and induces PPARγ activation in the aorta of apoE-deficient mice. - Abstract: The peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of lipid and glucose metabolism, and its activation is reported to suppress the progression of atherosclerosis. We have reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) activate PPARγ in macrophages. However, it is not yet known whether statins activate PPARγ in other vascular cells. In the present study, we investigated whether statins activate PPARγ in smooth muscle cells (SMCs) and endothelial cells (ECs) and thus mediate anti-atherosclerotic effects. Human aortic SMCs (HASMCs) and human umbilical vein ECs (HUVECs) were used in this study. Fluvastatin and pitavastatin activated PPARγ in HASMCs, but not in HUVECs. Statins induced cyclooxygenase-2 (COX-2) expression in HASMCs, but not in HUVECs. Moreover, treatment with COX-2-siRNA abrogated statin-mediated PPARγ activation in HASMCs. Statins suppressed migration and proliferation of HASMCs, and inhibited lipopolysaccharide-induced expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in HASMCs. These effects of statins were abrogated by treatment with PPARγ-siRNA. Treatment with statins suppressed atherosclerotic lesion formation in Apoe{sup −/−} mice. In addition, transcriptional activity of PPARγ and CD36 expression were increased, and the expression of MCP-1 and TNF-α was decreased, in the aorta of statin-treated Apoe{sup −/−} mice. In conclusion, statins mediate anti-atherogenic effects

  11. Modeling keratinocyte wound healing dynamics: Cell-cell adhesion promotes sustained collective migration.

    Science.gov (United States)

    Nardini, John T; Chapnick, Douglas A; Liu, Xuedong; Bortz, David M

    2016-07-01

    The in vitro migration of keratinocyte cell sheets displays behavioral and biochemical similarities to the in vivo wound healing response of keratinocytes in animal model systems. In both cases, ligand-dependent Epidermal Growth Factor Receptor (EGFR) activation is sufficient to elicit collective cell migration into the wound. Previous mathematical modeling studies of in vitro wound healing assays assume that physical connections between cells have a hindering effect on cell migration, but biological literature suggests a more complicated story. By combining mathematical modeling and experimental observations of collectively migrating sheets of keratinocytes, we investigate the role of cell-cell adhesion during in vitro keratinocyte wound healing assays. We develop and compare two nonlinear diffusion models of the wound healing process in which cell-cell adhesion either hinders or promotes migration. Both models can accurately fit the leading edge propagation of cell sheets during wound healing when using a time-dependent rate of cell-cell adhesion strength. The model that assumes a positive role of cell-cell adhesion on migration, however, is robust to changes in the leading edge definition and yields a qualitatively accurate density profile. Using RNAi for the critical adherens junction protein, α-catenin, we demonstrate that cell sheets with wild type cell-cell adhesion expression maintain migration into the wound longer than cell sheets with decreased cell-cell adhesion expression, which fails to exhibit collective migration. Our modeling and experimental data thus suggest that cell-cell adhesion promotes sustained migration as cells pull neighboring cells into the wound during wound healing. PMID:27105673

  12. Modeling keratinocyte wound healing dynamics: Cell-cell adhesion promotes sustained collective migration.

    Science.gov (United States)

    Nardini, John T; Chapnick, Douglas A; Liu, Xuedong; Bortz, David M

    2016-07-01

    The in vitro migration of keratinocyte cell sheets displays behavioral and biochemical similarities to the in vivo wound healing response of keratinocytes in animal model systems. In both cases, ligand-dependent Epidermal Growth Factor Receptor (EGFR) activation is sufficient to elicit collective cell migration into the wound. Previous mathematical modeling studies of in vitro wound healing assays assume that physical connections between cells have a hindering effect on cell migration, but biological literature suggests a more complicated story. By combining mathematical modeling and experimental observations of collectively migrating sheets of keratinocytes, we investigate the role of cell-cell adhesion during in vitro keratinocyte wound healing assays. We develop and compare two nonlinear diffusion models of the wound healing process in which cell-cell adhesion either hinders or promotes migration. Both models can accurately fit the leading edge propagation of cell sheets during wound healing when using a time-dependent rate of cell-cell adhesion strength. The model that assumes a positive role of cell-cell adhesion on migration, however, is robust to changes in the leading edge definition and yields a qualitatively accurate density profile. Using RNAi for the critical adherens junction protein, α-catenin, we demonstrate that cell sheets with wild type cell-cell adhesion expression maintain migration into the wound longer than cell sheets with decreased cell-cell adhesion expression, which fails to exhibit collective migration. Our modeling and experimental data thus suggest that cell-cell adhesion promotes sustained migration as cells pull neighboring cells into the wound during wound healing.

  13. Ablation of adenosine monophosphate-activated protein kinaseα1 in vascular smooth muscle cells promotes diet-induced atherosclerotic calcification in vivo

    Institute of Scientific and Technical Information of China (English)

    CAI Zhe-jun; DING Ye; ZHANG Miao; LU Qiu-lun; WU Sheng-nan; ZHU Huai-ping; SONG Ping; ZOU Ming-hui

    2016-01-01

    AIM:Atherosclerotic calcification is highly linked with plaque instability and cardiovascular events .Adenosine monophosphate-activated protein kinase ( AMPK) has been involved in the pathogenesis of various cardiovascular disease .The contributions of AMPKαsubunits to the development of atherosclerotic calcification in vivo remained unknown .We hypothesized that AMPKαsubunits may play a role in the development of atherosclerotic calcification .METHODS: Atherosclerotic calcification was generated by 24-week fed of western diet in ApoE-/-background mice .Calcification was evaluated in aortic roots and innominate arteries of ApoE-/-mice or in mice with dual deficiencies of ApoE and AMPKαsubunits globally ( AMPKα1 and AMPKα2 ) , or vascular smooth muscle cell ( VSMC)-specific or macrophage-specific knockout of AMPKα1 with atherosclerotic calcification pone diet . The mechanism of AMPKα1 in regulating Runx2 was further explored in human aortic VSMC .RESULTS: Ablation of AMPKα1 but not AMPKα2 in ApoE-/-background promoted atherosclerotic calcification with increased Runt -related transcription factor ( Runx2 ) expression in VSMC compared with ApoE-/-mice.Conversely, chronic administration of metformin, which activated AMPK, markedly reduced ath-erosclerotic calcification and Runx2 expression in ApoE-/-mice but had less effects in ApoE-/-/AMPKα1 -/-mice.Furthermore, VSMC-but not macrophage-specific deficiency of AMPKα1 in ApoE-/-background promoted atherosclerotic calcification in vivo com-pared with the controls .AMPKα1 silencing in human aortic VSMC prevented Runx 2 from proteasome degradation to trigger osteoblastic differentiation of VSMC .Conversely , activation of AMPK led to Runx 2 instability by inducing its small ubiquitin-like modifier modifi-cation (SUMOylation).Protein inhibitor of activated STAT-1 (PIAS1), the SUMO E3-ligase of Runx2, was directly phosphorylated by AMPKα1 at serine 510, to enhance its SUMO E3-ligase activity.Ablation of PIAS1

  14. Stem cells and chronic wound healing: state of the art

    Directory of Open Access Journals (Sweden)

    Leavitt T

    2016-03-01

    Full Text Available Tripp Leavitt, Michael S Hu, Clement D Marshall, Leandra A Barnes, Michael T Longaker, H Peter Lorenz Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA Abstract: Currently available treatments for chronic wounds are inadequate. A clearly effective therapy does not exist, and treatment is often supportive. This is largely because the cellular and molecular processes underlying failure of wound repair are still poorly understood. With an increase in comorbidities, such as diabetes and vascular disease, as well as an aging population, the incidence of these intractable wounds is expected to rise. As such, chronic wounds, which are already costly, are rapidly growing as a tremendous burden to the health-care system. Stem cells have garnered much interest as a therapy for chronic wounds due to their inherent ability to differentiate into multiple lineages and promote regeneration. Herein, we discuss the types of stem cells used for chronic wound therapy, as well as the proposed means by which they do so. In particular, we highlight mesenchymal stem cells (including adipose-derived stem cells, endothelial progenitor cells, and induced pluripotent stem cells. We include the results of recent in vitro and in vivo studies in both animal models and human clinical trials. Finally, we discuss the current studies to improve stem cell therapies and the limitations of stem cell-based therapeutics. Stem cells promise improved therapies for healing chronic wounds, but further studies that are well-designed with standardized protocols are necessary for fruition. Keywords: stem cells, chronic wounds, cell therapy, wound healing

  15. A Mechanistic-Based Healing Model for Self-Healing Glass Seals Used in Solid Oxide Fuel Cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Wei; Sun, Xin; Stephens, Elizabeth V.; Mastorakos, Ioannis; Khaleel, Mohammad A.; Zbib, Hussein M.

    2012-09-01

    The usage of self-healing glass as hermetic seals is a recent advancement in sealing technology development for the planar solid oxide fuel cells (SOFCs). Because of its capability of restoring the mechanical properties at elevated temperatures, the self-healing glass seal is expected to provide high reliability in maintaining the long-term structural integrity and functionality of SOFCs. In order to accommodate the design and to evaluate the effectiveness of such engineering seals under various thermo-mechanical operating conditions, computational modeling framework needs to be developed to accurately capture and predict the healing behavior of the glass material. In the present work, a mechanistic-based two-stage model was developed to study the stress and temperature-dependent crack healing of the self-healing glass materials. The model was first calibrated by experimental measurements combined with the kinetic Monte Carlo (kMC) simulation results and then implemented into the finite element analysis (FEA). The effects of various factors, i.e. stress, temperature, crack morphology, on the healing behavior of the glass were investigated and discussed.

  16. Evidence That Mast Cells Are Not Required for Healing of Splinted Cutaneous Excisional Wounds in Mice

    OpenAIRE

    Nauta, Allison C.; Grova, Monica; Montoro, Daniel T.; Zimmermann, Andrew; Tsai, Mindy; Geoffrey C Gurtner; Galli, Stephen J.; Longaker, Michael T.

    2013-01-01

    Wound healing is a complex biological process involving the interaction of many cell types to replace lost or damaged tissue. Although the biology of wound healing has been extensively investigated, few studies have focused on the role of mast cells. In this study, we investigated the possible role of mast cells in wound healing by analyzing aspects of cutaneous excisional wound healing in three types of genetically mast cell-deficient mice. We found that C57BL/6-KitW-sh/W-sh , WBB6F1-KitW/W-...

  17. Abnormal Cell Responses and Role of TNF-α in Impaired Diabetic Wound Healing

    Directory of Open Access Journals (Sweden)

    Fanxing Xu

    2013-01-01

    Full Text Available Impaired diabetic wound healing constitutes a major health problem. The impaired healing is caused by complex factors such as abnormal keratinocyte and fibroblast migration, proliferation, differentiation, and apoptosis, abnormal macrophage polarization, impaired recruitment of mesenchymal stem cells (MSCs and endothelial progenitor cells (EPCs, and decreased vascularization. Diabetes-enhanced and prolonged expression of TNF-α also contributes to impaired healing. In this paper, we discuss the abnormal cell responses in diabetic wound healing and the contribution of TNF-α.

  18. Abnormal Cell Responses and Role of TNF-α in Impaired Diabetic Wound Healing

    OpenAIRE

    Fanxing Xu; Chenying Zhang; Graves, Dana T.

    2013-01-01

    Impaired diabetic wound healing constitutes a major health problem. The impaired healing is caused by complex factors such as abnormal keratinocyte and fibroblast migration, proliferation, differentiation, and apoptosis, abnormal macrophage polarization, impaired recruitment of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), and decreased vascularization. Diabetes-enhanced and prolonged expression of TNF- α also contributes to impaired healing. In this paper, we discuss...

  19. Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro

    OpenAIRE

    Bussche, Leen; Harman, Rebecca M.; Syracuse, Bethany A; Plante, Eric L; Lu, Yen-Chun; Curtis, Theresa M; Ma, Minglin; Van de Walle, Gerlinde R

    2015-01-01

    Introduction The prevalence of impaired cutaneous wound healing is high and treatment is difficult and often ineffective, leading to negative social and economic impacts for our society. Innovative treatments to improve cutaneous wound healing by promoting complete tissue regeneration are therefore urgently needed. Mesenchymal stromal cells (MSCs) have been reported to provide paracrine signals that promote wound healing, but (i) how they exert their effects on target cells is unclear and (ii...

  20. ICAM-1 is necessary for epithelial recruitment of gammadelta T cells and efficient corneal wound healing.

    Science.gov (United States)

    Wound healing and inflammation are both significantly reduced in mice that lack gammadelta T cells. Here, the role of epithelial intercellular adhesion molecule-1 (ICAM-1) in gammadelta T cell migration in corneal wound healing was assessed. Wild-type mice had an approximate fivefold increase in epi...

  1. Effect of Low Level Ionizing Radiation on Endothelial Progenitor Cells in Atherosclerotic Patients with Lower Limb Ischemia

    International Nuclear Information System (INIS)

    Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality throughout the developed world (Williamson et al., 2012). Coronary artery disease (CAD) or atherosclerotic heart disease is a chronic life-threatening disease, which characterized by reducing blood supply to the heart as a result of the accumulation of atheromatous plaques within the walls of the arteries supplying the myocardium. Progressive atherosclerosis in the coronary arteries may lead to intimal thickening and eventual artery occlusion. Coronary artery occlusion can cause acute myocardial ischemia as a result of reduced oxygen supply or increased oxygen demand (Luthje and Andreas, 2008). Convincing evidence indicates that atherosclerosis is associated with endothelial dysfunction at the early stage of the disease process (Chiang et al., 2012). The endothelium is a dynamic cell layer that represents a physiological barrier between circulating blood and the surrounding tissues. Impaired endothelial function is a critical event in the initiation of atherosclerotic plaque development and thus may lead to vasoconstriction, vascular smooth muscle proliferation, hypercoagulability, thrombosis, and eventually, adverse cardiovascular events (Berger and Lavie, 2011). Asahara et al., (1997) described endothelial progenitor cells (EPC) in human peripheral blood. EPC are immature endothelial circulating cells mobilized from the bone marrow. These cells are involved in Introduction and aim of the work repairing the damaged endothelium and in facilitating neovascularization after ischemia (Rouhl et al., 2008). The role of EPC in health and disease is not understood completely. Most studies of healthy subjects and patients with coronary artery disease (CAD) report that the number and function of circulating EPC decrease with age and with the presence of classical vascular risk factors (Fadini et al., 2007). Recent studies suggested that EPCs play an important role in the risk of vascular

  2. Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice

    OpenAIRE

    Marrotte, Eric J.; Chen, Dan-Dan; Hakim, Jeffrey S.; Chen, Alex F.

    2010-01-01

    Amputation as a result of impaired wound healing is a serious complication of diabetes. Inadequate angiogenesis contributes to poor wound healing in diabetic patients. Endothelial progenitor cells (EPCs) normally augment angiogenesis and wound repair but are functionally impaired in diabetics. Here we report that decreased expression of manganese superoxide dismutase (MnSOD) in EPCs contributes to impaired would healing in a mouse model of type 2 diabetes. A decreased frequency of circulating...

  3. The effect of spiritual healing on in vitro tumour cell proliferation and viability - an experimental study

    DEFF Research Database (Denmark)

    Zachariae, R.; Hojgaard, L.; Zachariae, C.;

    2005-01-01

    ), and a nonadherent mouse B-lymphoid cell line (HB-94). Analyses of variance (ANOVAs) revealed no significant main or dose-related effects of spiritual healing compared to controls for either of the two cell lines or any of the assays (P-values between 0.09 and 0.96). When comparing healing and control across all......Alternative treatments such as spiritual healing and prayer are increasingly popular, especially among patients with life-threatening diseases such as cancer. According to theories of spiritual healing, this intervention is thought to influence living cells and organisms independently...... of the recipient's conscious awareness of the healer's intention. The aim of this study was to test the hypothesis that spiritual healing will reduce proliferation and viability of two cancer cell lines in vitro. Three controlled experiments were conducted with three different healers and randomised allocation...

  4. Activity of mesenchymal stem cells in therapies for chronic skin wound healing

    OpenAIRE

    Nuschke, Austin

    2013-01-01

    Chronic or non-healing skin wounds present an ongoing challenge in advanced wound care, particularly as the number of patients increases while technology aimed at stimulating wound healing in these cases remains inefficient. Mesenchymal stem cells (MSCs) have proved to be an attractive cell type for various cell therapies due to their ability to differentiate into various cell lineages, multiple donor tissue types, and relative resilience in ex-vivo expansion, as well as immunomodulatory effe...

  5. Orp8 deficiency in bone marrow-derived cells reduces atherosclerotic lesion progression in LDL receptor knockout mice.

    Directory of Open Access Journals (Sweden)

    Erik van Kampen

    Full Text Available INTRODUCTION: Oxysterol binding protein Related Proteins (ORPs mediate intracellular lipid transport and homeostatic regulation. ORP8 downregulates ABCA1 expression in macrophages and cellular cholesterol efflux to apolipoprotein A-I. In line, ORP8 knockout mice display increased amounts of HDL cholesterol in blood. However, the role of macrophage ORP8 in atherosclerotic lesion development is unknown. METHODS AND RESULTS: LDL receptor knockout (KO mice were transplanted with bone marrow (BM from ORP8 KO mice and C57Bl/6 wild type mice. Subsequently, the animals were challenged with a high fat/high cholesterol Western-type diet to induce atherosclerosis. After 9 weeks of Western-Type diet feeding, serum levels of VLDL cholesterol were increased by 50% in ORP8 KO BM recipients compared to the wild-type recipients. However, no differences were observed in HDL cholesterol. Despite the increase in VLDL cholesterol, lesions in mice transplanted with ORP8 KO bone marrow were 20% smaller compared to WT transplanted controls. In addition, ORP8 KO transplanted mice displayed a modest increase in the percentage of macrophages in the lesion as compared to the wild-type transplanted group. ORP8 deficient macrophages displayed decreased production of pro-inflammatory factors IL-6 and TNFα, decreased expression of differentiation markers and showed a reduced capacity to form foam cells in the peritoneal cavity. CONCLUSIONS: Deletion of ORP8 in bone marrow-derived cells, including macrophages, reduces lesion progression after 9 weeks of WTD challenge, despite increased amounts of circulating pro-atherogenic VLDL. Reduced macrophage foam cell formation and lower macrophage inflammatory potential are plausible mechanisms contributing to the observed reduction in atherosclerosis.

  6. Stem Cells in Skin Wound Healing: Are We There Yet?

    OpenAIRE

    Cerqueira, Mariana Teixeira; Pirraco, Rogério Pedro; Marques, Alexandra Pinto

    2016-01-01

    Significance: Cutaneous wound healing is a serious problem worldwide that affects patients with various wound types, resulting from burns, traumatic injuries, and diabetes. Despite the wide range of clinically available skin substitutes and the different therapeutic alternatives, delayed healing and scarring are often observed.

  7. Augmentation of cutaneous wound healing by pharmacologic mobilization of endogenous bone marrow stem cells.

    Science.gov (United States)

    Tolar, Jakub; McGrath, John A

    2014-09-01

    Novel therapeutic tools to accelerate wound healing would have a major impact on the overall burden of skin disease. Lin et al. demonstrate in mice that endogenous bone marrow stem cell mobilization, produced by a pharmacologic combination of AMD3100 and tacrolimus, leads to faster and better-quality wound healing, findings that have exciting potential for clinical translation. PMID:25120149

  8. Different wound healing properties of dermis, adipose, and gingiva mesenchymal stromal cells

    NARCIS (Netherlands)

    M.A. Boink; L.J. van den Broek; S. Roffel; K. Nazmi; J.G.M. Bolscher; A. Gefen; E.C.I. Veerman; S. Gibbs

    2016-01-01

    Oral wounds heal faster and with better scar quality than skin wounds. Deep skin wounds where adipose tissue is exposed, have a greater risk of forming hypertrophic scars. Differences in wound healing and final scar quality might be related to differences in mesenchymal stromal cells (MSC) and their

  9. Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications

    OpenAIRE

    Nkemcho Ojeh; Irena Pastar; Marjana Tomic-Canic; Olivera Stojadinovic

    2015-01-01

    The skin is the largest organ of the body and has an array of functions. Skin compartments, epidermis, and hair follicles house stem cells that are indispensable for skin homeostasis and regeneration. These stem cells also contribute to wound repair, resulting in restoration of tissue integrity and function of damaged tissue. Unsuccessful wound healing processes often lead to non-healing wounds. Chronic wounds are caused by depletion of stem cells and a variety of other cellular and molecular...

  10. Effect of allogeneic bone marrow derived stromal cells on induced third-degree skin burn healing in mouse

    Directory of Open Access Journals (Sweden)

    Leyla Soleymani

    2014-10-01

    Conclusion: This experimental modulation of wound healing suggests that bone marrow-derived stromal cells can significantly enhance the rate of wound healing possibly through stimulation of granulation tissue, angiogenesis, fibroblast proliferation and collagen deposition.

  11. Oleic acid induces smooth muscle foam cell formation and enhances atherosclerotic lesion development via CD36

    OpenAIRE

    Tang Bing; Li; Yang Dachun; Ma Shuangtao; Yang Yongjian

    2011-01-01

    Abstract Background Elevated plasma free fatty acid (FFA) levels have been linked to the development of atherosclerosis. However, how FFA causes atherosclerosis has not been determined. Because fatty acid translocase (FAT/CD36) is responsible for the uptake of FFA, we hypothesized that the atherogenic effects of FFA may be mediated via CD36. Results We tested this hypothesis using cultured rat aortic smooth muscle cells (SMCs) treated with oleic acid (OA). We found that OA induces lipid accum...

  12. Asiaticoside enhances normal human skin cell migration, attachment and growth in vitro wound healing model.

    Science.gov (United States)

    Lee, Jeong-Hyun; Kim, Hye-Lee; Lee, Mi Hee; You, Kyung Eun; Kwon, Byeong-Ju; Seo, Hyok Jin; Park, Jong-Chul

    2012-10-15

    Wound healing proceeds through a complex collaborative process involving many types of cells. Keratinocytes and fibroblasts of epidermal and dermal layers of the skin play prominent roles in this process. Asiaticoside, an active component of Centella asiatica, is known for beneficial effects on keloid and hypertrophic scar. However, the effects of this compound on normal human skin cells are not well known. Using in vitro systems, we observed the effects of asiaticoside on normal human skin cell behaviors related to healing. In a wound closure seeding model, asiaticoside increased migration rates of skin cells. By observing the numbers of cells attached and the area occupied by the cells, we concluded that asiaticoside also enhanced the initial skin cell adhesion. In cell proliferation assays, asiaticoside induced an increase in the number of normal human dermal fibroblasts. In conclusion, asiaticoside promotes skin cell behaviors involved in wound healing; and as a bioactive component of an artificial skin, may have therapeutic value.

  13. Dietary supplementation with Cyperus esculentus L (tiger nut tubers attenuated atherosclerotic lesion in apolipoprotein E knockout mouse associated with inhibition of inflammatory cell responses

    Directory of Open Access Journals (Sweden)

    Mohamed L.  Salem

    2005-01-01

    Full Text Available Atherosclerosis is a pathological process, where recruitment of mononuclear cells results in the growth of fibro-fatty plaques. Apolipoprotein E (ApoE is a legend for the uptake of lipoproteins, and deficiency of ApoE leads to the accumulation of low-density lipoprotein. Utilizing ApoE-/- mouse, which spontaneously develop atherosclerosis on low-fat chow diets, the present study showed that feeding these mice on a diet supplemented with the whole tubers of Cyperus esculentus L (tiger nut resulted in attenuation of the development of atherosclerotic lesions. The anti-atherosclerotic effect was associated with a decrease in the number of monocytes, macrophages and dendritic cells in blood, and the expression of IL-2Rαand LFA-1 by these cells. Further, in vitro proliferation of blood and spleen cells from tiger nut-fed ApoE-/- mice showed lower proliferation in responses to ConA and LPS, a T and B cell mitogen, respectively. Further, in vitro treatment of blood and spleen cells with water or ethanol extracts of tiger nut markedly increased their proliferation in response to ConA. Collectively, these data indicate that ingredients of tiger nut tubers exhibit anti-inflammatory properties upon inflammation, and immunostimulatory effects in immunocompetent hosts.

  14. SCF increases in utero-labeled stem cells migration and improves wound healing.

    Science.gov (United States)

    Zgheib, Carlos; Xu, Junwang; Mallette, Andrew C; Caskey, Robert C; Zhang, Liping; Hu, Junyi; Liechty, Kenneth W

    2015-01-01

    Diabetic skin wounds lack the ability to heal properly and constitute a major and significant complication of diabetes. Nontraumatic lower extremity amputations are the number one complication of diabetic skin wounds. The complexity of their pathophysiology requires an intervention at many levels to enhance healing and wound closure. Stem cells are a promising treatment for diabetic skin wounds as they have the ability to correct abnormal healing. Stem cell factor (SCF), a chemokine expressed in the skin, can induce stem cells migration, however the role of SCF in diabetic skin wound healing is still unknown. We hypothesize that SCF would correct the impairment and promote the healing of diabetic skin wounds. Our results show that SCF improved wound closure in diabetic mice and increased HIF-1α and vascular endothelial growth factor (VEGF) expression levels in these wounds. SCF treatment also enhanced the migration of red fluorescent protein (RFP)-labeled skin stem cells via in utero intra-amniotic injection of lenti-RFP at E8. Interestingly these RFP+ cells are present in the epidermis, stain negative for K15, and appear to be distinct from the already known hair follicle stem cells. These results demonstrate that SCF improves diabetic wound healing in part by increasing the recruitment of a unique stem cell population present in the skin.

  15. Concise Review: Clinical Translation of Wound Healing Therapies Based on Mesenchymal Stem Cells

    OpenAIRE

    Jackson, Wesley M.; Nesti, Leon J.; Tuan, Rocky S.

    2011-01-01

    There is enormous worldwide demand for therapies to promote the efficient resolution of hard-to-heal wounds with minimal appearance of scarring. Recent in vitro studies with mesenchymal stem cells (MSCs) have identified numerous mechanisms by which these cells can promote the process of wound healing, and there is significant interest in the clinical translation of an MSC-based therapy to promote dermal regeneration. This review provides a systematic analysis of recent preclinical and clinica...

  16. Corals use similar immune cells and wound-healing processes as those of higher organisms.

    Directory of Open Access Journals (Sweden)

    Caroline V Palmer

    Full Text Available Sessile animals, like corals, frequently suffer physical injury from a variety of sources, thus wound-healing mechanisms that restore tissue integrity and prevent infection are vitally important for defence. Despite the ecological importance of reef-building corals, little is known about the cells and processes involved in wound healing in this group or in phylogenetically basal metazoans in general. A histological investigation into wound healing of the scleractinian coral Porites cylindrica at 0 h, 6 h, 24 h and 48 h after injury revealed differences in cellular components between injured and healthy tissues. Cell counts of the obligate endosymbiont, Symbiodinium, and melanin volume fraction analysis revealed rapid declines in both Symbiodinium abundance and tissue cross-sectional area occupied by melanin-containing granular cells after injury. Four phases of wound healing were identified, which are similar to phases described for both vertebrates and invertebrates. The four phases included (i plug formation via the degranulation of melanin-containing granular cells; (ii immune cell infiltration (inflammation; (iii granular tissue formation (proliferation; and (iv maturation. This study provides detailed documentation of the processes involved in scleractinian wound healing for the first time and further elucidates the roles of previously-described immune cells, such as fibroblasts. These results demonstrate the conservation of wound healing processes from anthozoans to humans.

  17. Cytocompatible, Photoreversible, and Self-Healing Hydrogels for Regulating Bone Marrow Stromal Cell Differentiation.

    Science.gov (United States)

    Yu, Lianlian; Xu, Kaige; Ge, Liangpeng; Wan, Wenbing; Darabi, Ali; Xing, Malcolm; Zhong, Wen

    2016-09-01

    Photo-crosslinking and self-healing have received considerable attention for the design of intelligent materials. A novel photostimulated, self-healing, and cytocompatible hydrogel system is reported. A coumarin methacrylate crosslinker is synthesized to modify the polyacrylamide-based hydrogels. With the [2+2] cyclo-addition of coumarin moieties, the hydrogels exhibit excellent self-healing capacity when they are exposed to light with wavelengths at 280 and 365 nm, respectively. To enhance cell compatibility, a poly (amidoamine) crosslinker is also synthesized. Variations in light exposure times and irradiation wavelengths are found to alter the self-healing property of the hydrogels. The hydrogels are shown to induce a regular cellular pattern. The hydrogels are used to regulate bone marrow stromal cells differentiation. The relative mRNA expressions are recorded to monitor the osteogenic differentiation of the cells. PMID:27280860

  18. Contribution of Invariant Natural Killer T Cells to Skin Wound Healing.

    Science.gov (United States)

    Tanno, Hiromasa; Kawakami, Kazuyoshi; Ritsu, Masae; Kanno, Emi; Suzuki, Aiko; Kamimatsuno, Rina; Takagi, Naoyuki; Miyasaka, Tomomitsu; Ishii, Keiko; Imai, Yoshimichi; Maruyama, Ryoko; Tachi, Masahiro

    2015-12-01

    In the present study, we determined the contribution of invariant natural killer T (iNKT) cells to the skin wound healing process. In iNKT cell-deficient (Jα18KO) mice lacking iNKT cells, wound closure was significantly delayed compared with wild-type mice. Collagen deposition, expression of α-smooth muscle actin and CD31, and wound breaking strength were significantly attenuated in Jα18KO mice. The adoptive transfer of liver mononuclear cells from wild-type but not from Jα18KO or interferon (IFN)-γ gene-disrupted (IFN-γKO) mice resulted in the reversal of this impaired wound healing in Jα18KO mice. IFN-γ expression was induced in the wounded tissues, which was significantly decreased at 6, 12, and 24 hours, but increased on day 3 after wounding in Jα18KO mice. The main source of the late-phase IFN-γ production in Jα18KO mice were neutrophils rather than NK cells and T cells. Administration of α-galactosylceramide, an activator of iNKT cells, resulted in the acceleration of wound healing on day 3 in wild-type mice. This effect was not observed in IFN-γKO mice. These results indicate that iNKT cells play important roles in wound healing. The iNKT cell-induced IFN-γ production may regulate the wound healing process in the early phase.

  19. Primary culture of endothelial cells from atherosclerotic human aorta. Part 1. Identification, morphological and ultrastructural characteristics of two endothelial cell subpopulations.

    Science.gov (United States)

    Antonov, A S; Nikolaeva, M A; Klueva, T S; Romanov YuA; Babaev, V R; Bystrevskaya, V B; Perov, N A; Repin, V S; Smirnov, V N

    1986-01-01

    Endothelial cells (EC) were harvested by 0.1% collagenase treatment for adult human thoracic aortas obtained 1-3 h after sudden death. At least 35-70% of EC were removed from the intimal surface of aorta, 90-95% of them being viable. Plating efficiency was 70-80%. Monolayer formation was achieved at a seeding density of 5-8 X 10(2) cells/mm2. The cells were identified as endothelium by the presence of Factor VIII antigen, Weigel-Palade bodies and typically endothelial morphology at confluence. Unlike endothelial cultures derived from human umbilical veins and infant aortas, primary cultures obtained from human adult aortas contain multinuclear EC with Factor VIII antigen and Weibel-Palade bodies. The number of multinuclear EC in cultures isolated from aortas affected by atherosclerosis was 2-fold higher (P less than 0.05) than in cultures obtained from grossly normal aortas taken from donors of the same age. EC with numerous lipid inclusions revealed by oil-red-O staining were present in all the EC primary cultures derived from aortas affected by atherosclerosis. No oil-red-O-positive cells were detected among the EC cultured from infant aorta, aorta of young donors, and umbilical vein. An electron microscopic examination of EC from atherosclerotic aorta in culture and in situ failed to reveal any ultrastructural peculiarities distinguishing multinuclear EC from the mononuclear EC. PMID:3004520

  20. Paracrine effects of stem cells in wound healing and cancer progression

    OpenAIRE

    DITTMER, JÜRGEN; Leyh, Benjamin

    2014-01-01

    Stem cells play an important role in tissue repair and cancer development. The capacity to self-renew and to differentiate to specialized cells allows tissue-specific stem cells to rebuild damaged tissue and cancer stem cells to initiate and promote cancer. Mesenchymal stem cells, attracted to wounds and cancer, facilitate wound healing and support cancer progression primarily by secreting bioactive factors. There is now growing evidence that, like mesenchymal stem cells, also tissue-specific...

  1. Knockdown of SVCT2 impairs in-vitro cell attachment, migration and wound healing in bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Rajnikumar Sangani

    2014-03-01

    Full Text Available Bone marrow stromal cell (BMSC adhesion and migration are fundamental to a number of pathophysiologic processes, including fracture and wound healing. Vitamin C is beneficial for bone formation, fracture repair and wound healing. However, the role of the vitamin C transporter in BMSC adhesion, migration and wound healing is not known. In this study, we knocked-down the sodium-dependent vitamin C transporter, SVCT2, the only known transporter of vitamin C in BMSCs, and performed cell adhesion, migration, in-vitro scratch wound healing and F-actin re-arrangement studies. We also investigated the role of oxidative stress on the above processes. Our results demonstrate that both oxidative stress and down-regulation of SVCT2 decreased cell attachment and spreading. A trans-well cell migration assay showed that vitamin C helped in BMSC migration and that knockdown of SVCT2 decreased cell migration. In the in-vitro scratch wound healing studies, we established that oxidative stress dose-dependently impairs wound healing. Furthermore, the supplementation of vitamin C significantly rescued the BMSCs from oxidative stress and increased wound closing. The knockdown of SVCT2 in BMSCs strikingly decreased wound healing, and supplementing with vitamin C failed to rescue cells efficiently. The knockdown of SVCT2 and induction of oxidative stress in cells produced an alteration in cytoskeletal dynamics. Signaling studies showed that oxidative stress phosphorylated members of the MAP kinase family (p38 and that vitamin C inhibited their phosphorylation. Taken together, these results indicate that both the SVCT2 transporter and oxidative stress play a vital role in BMSC attachment, migration and cytoskeletal re-arrangement. BMSC-based cell therapy and modulation of SVCT2 could lead to a novel therapeutic approach that enhances bone remodeling, fracture repair and wound healing in chronic disease conditions.

  2. eDNA: A Bio-Inspired Reconfigurable Hardware Cell Architecture Supporting Self-organisation and Self-healing

    DEFF Research Database (Denmark)

    Boesen, Michael Reibel; Madsen, Jan

    2009-01-01

    This paper presents the concept of a biological inspired reconfigurable hardware cell architecture which supports self-organisation and self-healing. Two fundamental processes in biology, namely fertilization-to-birth and cell self-healing have inspired the development of this cell architecture. ...

  3. A possible link between loading, inflammation and healing: Immune cell populations during tendon healing in the rat.

    Science.gov (United States)

    Blomgran, Parmis; Blomgran, Robert; Ernerudh, Jan; Aspenberg, Per

    2016-01-01

    Loading influences tendon healing, and so does inflammation. We hypothesized that the two are connected. 48 rats underwent Achilles tendon transection. Half of the rats received Botox injections into calf muscles to reduce mechanical loading. Cells from the regenerating tissue were analyzed by flow cytometry. In the loaded group, the regenerating tissue contained 83% leukocytes (CD45(+)) day 1, and 23% day 10. The M1/M2 macrophage ratio (CCR7/CD206) peaked at day 3, while T helper (CD3(+)CD4(+)) and Treg cells (CD25(+) Foxp3(+)) increased over time. With Botox, markers associated with down-regulation of inflammation were more common day 5 (CD163, CD206, CD25, Foxp3), and M1 or M2 macrophages and Treg cells were virtually absent day 10, while still present with full loading. The primary variable, CCR7/CD206 ratio day 5, was higher with full loading (p = 0.001) and the Treg cell fraction was lower (p < 0.001). Free cage activity loading is known to increase size and strength of the tendon in this model compared to Botox. Loading now appeared to delay the switch to an M2 type of inflammation with more Treg cells. It seems a prolonged M1 phase due to loading might make the tendon regenerate bigger. PMID:27405922

  4. NK cells modulate the inflammatory response to corneal epithelial abrasion and thereby support wound healing

    Science.gov (United States)

    Natural killer cells are lymphocytes of the innate immune system that have crucial cytotoxic and regulatory roles in adaptive immunity and inflammation. Herein, we consider a role for these cells in corneal wound healing. After a 2-mm central epithelial abrasion of the mouse cornea, a subset of clas...

  5. Wound Healing and Cancer Stem Cells: Inflammation as a Driver of Treatment Resistance in Breast Cancer

    Science.gov (United States)

    Arnold, Kimberly M; Opdenaker, Lynn M; Flynn, Daniel; Sims-Mourtada, Jennifer

    2015-01-01

    The relationship between wound healing and cancer has long been recognized. The mechanisms that regulate wound healing have been shown to promote transformation and growth of malignant cells. In addition, chronic inflammation has been associated with malignant transformation in many tissues. Recently, pathways involved in inflammation and wound healing have been reported to enhance cancer stem cell (CSC) populations. These cells, which are highly resistant to current treatments, are capable of repopulating the tumor after treatment, causing local and systemic recurrences. In this review, we highlight proinflammatory cytokines and developmental pathways involved in tissue repair, whose deregulation in the tumor microenvironment may promote growth and survival of CSCs. We propose that the addition of anti-inflammatory agents to current treatment regimens may slow the growth of CSCs and improve therapeutic outcomes. PMID:25674014

  6. Decreased Regulatory T Cells in Vulnerable Atherosclerotic Lesions: Imbalance between Pro- and Anti-Inflammatory Cells in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ilonka Rohm

    2015-01-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease of the arterial wall in which presentation of autoantigens by dendritic cells (DCs leads to the activation of T cells. Anti-inflammatory cells like Tregs counterbalance inflammation in atherogenesis. In our study, human carotid plaque specimens were classified as stable (14 and unstable (15 according to established morphological criteria. Vessel specimens (n=12 without any signs of atherosclerosis were used as controls. Immunohistochemical staining was performed to detect different types of DCs (S100, fascin, CD83, CD209, CD304, and CD123, proinflammatory T cells (CD3, CD4, CD8, and CD161, and anti-inflammatory Tregs (FoxP3. The following results were observed: in unstable lesions, significantly higher numbers of proinflammatory cells like DCs, T helper cells, cytotoxic T cells, and natural killer cells were detected compared to stable plaques. Additionally, there was a significantly higher expression of HLA-DR and more T cell activation (CD25, CD69 in unstable lesions. On the contrary, unstable lesions contained significantly lower numbers of Tregs. Furthermore, a significant inverse correlation between myeloid DCs and Tregs was shown. These data suggest an increased inflammatory state in vulnerable plaques resulting from an imbalance of the frequency of local pro- and anti-inflammatory immune cells.

  7. [Advances in the mechanism of mesenchymal stem cells in promoting wound healing].

    Science.gov (United States)

    Zhu, Wenjing; Sun, Haobo; Lyu, Guozhong

    2015-12-01

    Mesenchymal stem cells possess the ability of self-renewal and multiple differentiation potential, thus exert immunomodulatory effect during tissue repair. Mesenchymal stem cells can stimulate angiogenesis and promote tissue repair through transdifferentiation and secreting a variety of growth factors and cytokines. This review outlines the advances in the mechanism of mesenchymal stem cells in promoting wound healing, including alleviation of inflammatory response, induction of angiogenesis, and promotion of migration of mesenchymal stem cells to the site of tissue injury.

  8. Endothelial Dysfunction and Diabetes: Effects on Angiogenesis, Vascular Remodeling, and Wound Healing

    OpenAIRE

    Gopi Krishna Kolluru; Bir, Shyamal C.; Kevil, Christopher G.

    2012-01-01

    Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia due to lack of or resistance to insulin. Patients with DM are frequently afflicted with ischemic vascular disease or wound healing defect. It is well known that type 2 DM causes amplification of the atherosclerotic process, endothelial cell dysfunction, glycosylation of extracellular matrix proteins, and vascular denervation. These complications ultimately lead to impairment of neovascularizati...

  9. Sundew-Inspired Adhesive Hydrogels Combined with Adipose-Derived Stem Cells for Wound Healing.

    Science.gov (United States)

    Sun, Leming; Huang, Yujian; Bian, Zehua; Petrosino, Jennifer; Fan, Zhen; Wang, Yongzhong; Park, Ki Ho; Yue, Tao; Schmidt, Michael; Galster, Scott; Ma, Jianjie; Zhu, Hua; Zhang, Mingjun

    2016-01-27

    The potential to harness the unique physical, chemical, and biological properties of the sundew (Drosera) plant's adhesive hydrogels has long intrigued researchers searching for novel wound-healing applications. However, the ability to collect sufficient quantities of the sundew plant's adhesive hydrogels is problematic and has eclipsed their therapeutic promise. Inspired by these natural hydrogels, we asked if sundew-inspired adhesive hydrogels could overcome the drawbacks associated with natural sundew hydrogels and be used in combination with stem-cell-based therapy to enhance wound-healing therapeutics. Using a bioinspired approach, we synthesized adhesive hydrogels comprised of sodium alginate, gum arabic, and calcium ions to mimic the properties of the natural sundew-derived adhesive hydrogels. We then characterized and showed that these sundew-inspired hydrogels promote wound healing through their superior adhesive strength, nanostructure, and resistance to shearing when compared to other hydrogels in vitro. In vivo, sundew-inspired hydrogels promoted a "suturing" effect to wound sites, which was demonstrated by enhanced wound closure following topical application of the hydrogels. In combination with mouse adipose-derived stem cells (ADSCs) and compared to other therapeutic biomaterials, the sundew-inspired hydrogels demonstrated superior wound-healing capabilities. Collectively, our studies show that sundew-inspired hydrogels contain ideal properties that promote wound healing and suggest that sundew-inspired-ADSCs combination therapy is an efficacious approach for treating wounds without eliciting noticeable toxicity or inflammation. PMID:26731614

  10. Prolonged Survival of Transplanted Osteoblastic Cells Does Not Directly Accelerate the Healing of Calvarial Bone Defects.

    Science.gov (United States)

    Kitami, Megumi; Kaku, Masaru; Rocabado, Juan Marcelo Rosales; Ida, Takako; Akiba, Nami; Uoshima, Katsumi

    2016-09-01

    Considering the increased interest in cell-based bone regeneration, it is necessary to reveal the fate of transplanted cells and their substantive roles in bone regeneration. The aim of this study was to analyze the fate of transplanted cells and the effect of osteogenic cell transplantation on calvarial bone defect healing. An anti-apoptotic protein, heat shock protein (HSP) 27, was overexpressed in osteoblasts. Then, the treated osteoblasts were transplanted to calvarial bone defect and their fate was analyzed to evaluate the significance of transplanted cell survival. Transient overexpression of Hsp27 rescued MC3T3-E1 osteoblastic cells from H2 O2 -induced apoptosis without affecting osteoblastic differentiation in culture. Transplantation of Hsp27-overexpressing cells, encapsulated in collagen gel, showed higher proliferative activity, and fewer apoptotic cells in comparison with control cells. After 4-week of transplantation, both control cell- and Hsp27 overexpressed cell-transplanted groups showed significantly higher new bone formation in comparison with cell-free gel-transplantation group. Interestingly, the prolonged survival of transplanted osteoblastic cells by Hsp27 did not provide additional effect on bone healing. The transplanted cells in collagen gel survived for up to 4-week but did not differentiate into bone-forming osteoblasts. In conclusion, cell-containing collagen gel accelerated calvarial bone defect healing in comparison with cell-free collagen gel. However, prolonged survival of transplanted cells by Hsp27 overexpression did not provide additional effect. These results strongly indicate that cell transplantation-based bone regeneration cannot be explained only by the increment of osteogenic cells. Further studies are needed to elucidate the practical roles of transplanted cells that will potentiate successful bone regeneration. J. Cell. Physiol. 231: 1974-1982, 2016. © 2016 Wiley Periodicals, Inc.

  11. Increased Number of Langerhans Cells in the Epidermis of Diabetic Foot Ulcers Correlates with Healing Outcome

    OpenAIRE

    Stojadinovic, Olivera; Yin, Natalie; Lehmann, Janin; Pastar, Irena; Kirsner, Robert S.; Tomic-Canic, Marjana

    2013-01-01

    Langerhans cells (LCs) are a specialized subset of epidermal dendritic cells. They represent one of the first cells of immunological barrier and play an important role during the inflammatory phase of acute wound healing. Despite considerable progress in our understanding of the immunopathology of diabetes mellitus and its associated co-morbidities such as diabetic foot ulcers (DFUs), considerable gaps in our knowledge exist. In this study, we utilized the human ex vivo wound model and confir...

  12. Water fluxes through aquaporin-9 prime epithelial cells for rapid wound healing

    DEFF Research Database (Denmark)

    Karlsson, T.; Lagerholm, B. C.; Vikstrom, E.;

    2013-01-01

    Cells move along surfaces both as single cells and multi-cellular units. Recent research points toward pivotal roles for water flux through aquaporins (AQPs) in single cell migration. Their expression is known to facilitate this process by promoting rapid shape changes. However, little is known...... wound healing based on AQP-induced swelling and expansion of the monolayer. (C) 2012 Elsevier Inc. All rights reserved....

  13. Role of endothelial progenitor cells and inflammatory cytokines in healing of diabetic foot ulcers.

    Directory of Open Access Journals (Sweden)

    Francesco Tecilazich

    Full Text Available BACKGROUND: To evaluate changes in endothelial progenitor cells (EPCs and cytokines in patients with diabetic foot ulceration (DFU in association with wound healing. METHODS: We studied healthy subjects, diabetic patients not at risk of DFU, at risk of DFU and with active DFU. We prospectively followed the DFU patients over a 12-week period. We also investigated similar changes in diabetic rabbit and mouse models of wound healing. RESULTS: All EPC phenotypes except the kinase insert domain receptor (KDR(+CD133(+ were reduced in the at risk and the DFU groups compared to the controls. There were no major EPC differences between the control and not at risk group, and between the at risk and DFU groups. Serum stromal-cell derived factor-1 (SDF-1 and stem cell factor (SCF were increased in DFU patients. DFU patients who healed their ulcers had lower CD34(+KDR(+ count at visits 3 and 4, serum c-reactive protein (CRP and granulocyte-macrophage colony-stimulating factor (GM-CSF at visit 1, interleukin-1 (IL-1 at visits 1 and 4. EPCs tended to be higher in both diabetic animal models when compared to their non-diabetic counterparts both before and ten days after wounding. CONCLUSIONS: Uncomplicated diabetes does not affect EPCs. EPCs are reduced in patients at risk or with DFU while complete wound healing is associated with CD34(+KDR(+ reduction, suggesting possible increased homing. Low baseline CRP, IL-1α and GM-CSF serum levels were associated with complete wound healing and may potentially serve as prognostic markers of DFU healing. No animal model alone is representative of the human condition, indicating the need for multiple experimental models.

  14. Human umbilical mesenchymal stem cells conditioned medium promote primary wound healing regeneration

    Directory of Open Access Journals (Sweden)

    Dwi Liliek Kusindarta

    2016-06-01

    Full Text Available Aim: This research was conducted to clarify the capability of human umbilical mesenchymal stem cells conditioned medium (HU-MSCM to promote regenerations of primary wound healing on the incision skin injury. Materials and Methods: In this study, two approaches in vitro and in vivo already done. On in vitro analysis, tube formation was performed using HU vein endothelial cells in the presence of HU-MSCM, in some experiments cells line was incubated prior the presence of lipopolysaccharide and HU-MSCM then apoptosis assay was performed. Furthermore, in vivo experiments 12 female rats (Rattus norvegicus were used after rats anesthetized, 7 mm wound was made by incision on the left side of the body. The wound was treated with HU-MSCM containing cream, povidone iodine was run as a control. Wound healing regenerations on the skin samples were visualized by hematoxylin-eosin staining. Results: In vitro models elucidate HU-MSCM may decreasing inflammation at the beginning of wound healing, promote cell migration and angiogenesis. In addition in vivo models show that the incision length on the skin is decreasing and more smaller, HE staining describe decreasing of inflammation phase, increasing of angiogenesis, accelerate fibroplasia, and maturation phase. Conclusions: Taken together our observation indicates that HU-MSCM could promote the acceleration of skin tissue regenerations in primary wound healing process.

  15. Substance P combined with epidermal stem cells promotes wound healing and nerve regeneration in diabetes mellitus

    OpenAIRE

    Fei-bin Zhu; Xiang-jing Fang; De-wu Liu; Ying Shao; Hong-yan Zhang; Yan Peng; Qing-ling Zhong; Yong-tie Li; De-ming Liu

    2016-01-01

    Exogenous substance P accelerates wound healing in diabetes, but the mechanism remains poorly understood. Here, we established a rat model by intraperitoneally injecting streptozotocin. Four wounds (1.8 cm diameter) were drilled using a self-made punch onto the back, bilateral to the vertebral column, and then treated using amniotic membrane with epidermal stem cells and/or substance P around and in the middle of the wounds. With the combined treatment the wound-healing rate was 100% at 14 da...

  16. Mesenchymal Stem Cells for Enhancing Biologic Healing after Anterior Cruciate Ligament Injuries.

    Science.gov (United States)

    Jang, Ki-Mo; Lim, Hong Chul; Bae, Ji Hoon

    2015-01-01

    Arthroscopic anterior cruciate ligament (ACL) reconstruction using tendon grafts is the current gold standard for the treatment of ACL tears in active patients. However, many patients still experience residual knee instability, knee pain and progressive cartilage degeneration following ACL reconstruction. Recent developments in mesenchymal stem cell (MSC)-based approaches for treating musculoskeletal injuries have led to the application of MSCs for enhancing healing after ACL injuries. The purpose of this article is to review recent pre-clinical and clinical studies using MSCs for the enhancement of biologic healing of ACL injuries. Because of the success of pre-clinical studies, MSC-based approaches are now thought to be promising treatment options for enhancing biologic healing of ACL grafts and restoring the functional properties to the levels of the native ACL, and ultimately improving clinical outcomes.

  17. Can crystalline phases be self-healing sealants for solid oxide fuel cells?

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Teng; Tang, Dian [Institute for Materials Research, Fuzhou University, Fuzhou, Fujian 350108 (China); Yang, Hiswen [Department of Materials Science and Engineering, National United University, Miao-Li 36003 (China)

    2011-02-01

    The poor thermodynamic and thermal stability of self-healing glass sealants restrict their applications in planar solid oxide fuel cells (SOFCs). In this paper, a calcium borate crystalline is prepared by melting-quench and a subsequent crystallization. The crystalline phases include CaB{sub 4}O{sub 7} and CaB{sub 2}O{sub 4}. The in situ observation reveals that the micro-indentation on the surface of such crystalline can be healed when heating from room temperature to 840 C at a heating rate of 40 C min{sup -1}. Combining with the improved thermal stability, the crystalline sealant with desired self-healing property, at the operational temperature of SOFCs (e.g., 700-900 C), provides additional solution for the sealing challenge of SOFCs. (author)

  18. A cell-regulatory mechanism involving feedback between contraction and tissue formation guides wound healing progression.

    Directory of Open Access Journals (Sweden)

    Clara Valero

    Full Text Available Wound healing is a process driven by cells. The ability of cells to sense mechanical stimuli from the extracellular matrix that surrounds them is used to regulate the forces that cells exert on the tissue. Stresses exerted by cells play a central role in wound contraction and have been broadly modelled. Traditionally, these stresses are assumed to be dependent on variables such as the extracellular matrix and cell or collagen densities. However, we postulate that cells are able to regulate the healing process through a mechanosensing mechanism regulated by the contraction that they exert. We propose that cells adjust the contraction level to determine the tissue functions regulating all main activities, such as proliferation, differentiation and matrix production. Hence, a closed-regulatory feedback loop is proposed between contraction and tissue formation. The model consists of a system of partial differential equations that simulates the evolution of fibroblasts, myofibroblasts, collagen and a generic growth factor, as well as the deformation of the extracellular matrix. This model is able to predict the wound healing outcome without requiring the addition of phenomenological laws to describe the time-dependent contraction evolution. We have reproduced two in vivo experiments to evaluate the predictive capacity of the model, and we conclude that there is feedback between the level of cell contraction and the tissue regenerated in the wound.

  19. Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications

    Directory of Open Access Journals (Sweden)

    Nkemcho Ojeh

    2015-10-01

    Full Text Available The skin is the largest organ of the body and has an array of functions. Skin compartments, epidermis, and hair follicles house stem cells that are indispensable for skin homeostasis and regeneration. These stem cells also contribute to wound repair, resulting in restoration of tissue integrity and function of damaged tissue. Unsuccessful wound healing processes often lead to non-healing wounds. Chronic wounds are caused by depletion of stem cells and a variety of other cellular and molecular mechanisms, many of which are still poorly understood. Current chronic wound therapies are limited, so the search to develop better therapeutic strategies is ongoing. Adult stem cells are gaining recognition as potential candidates for numerous skin pathologies. In this review, we will discuss epidermal and other stem cells present in the skin, and highlight some of the therapeutic applications of epidermal stem cells and other adult stem cells as tools for cell/scaffold-based therapies for non-healing wounds and other skin disorders. We will also discuss emerging concepts and offer some perspectives on how skin tissue-engineered products can be optimized to provide efficacious therapy in cutaneous repair and regeneration.

  20. The effect of spiritual healing on in vitro tumour cell proliferation and viability--an experimental study

    DEFF Research Database (Denmark)

    Zachariae, R; Højgaard, L; Zachariae, C;

    2005-01-01

    ), and a nonadherent mouse B-lymphoid cell line (HB-94). Analyses of variance (ANOVAs) revealed no significant main or dose-related effects of spiritual healing compared to controls for either of the two cell lines or any of the assays (P-values between 0.09 and 0.96). When comparing healing and control across all......Alternative treatments such as spiritual healing and prayer are increasingly popular, especially among patients with life-threatening diseases such as cancer. According to theories of spiritual healing, this intervention is thought to influence living cells and organisms independently...... of the recipient's conscious awareness of the healer's intention. The aim of this study was to test the hypothesis that spiritual healing will reduce proliferation and viability of two cancer cell lines in vitro. Three controlled experiments were conducted with three different healers and randomised allocation...

  1. Therapeutic potential of bone marrow-derived mesenchymal stem cells in cutaneous wound healing

    Directory of Open Access Journals (Sweden)

    Jerry S Chen

    2012-07-01

    Full Text Available Despite advances in wound care, many wounds never heal and become chronic problems that result in significant morbidity and mortality to the patient. Cellular therapy for cutaneous wounds has recently come under investigation as a potential treatment modality for impaired wound healing. Bone marrow-derived mesenchymal stem cells (MSCs are a promising source of adult progenitor cells for cytotherapy as they are easy to isolate and expand and have been shown to differentiate into various cell lineages. Early studies have demonstrated that MSCs may enhance epithelialization, granulation tissue formation, and neovascularization resulting in accelerated wound closure. It is currently unclear if these effects are mediated through cellular differentiation or by secretion of cytokines and growth factors. This review discusses the proposed biological contributions of MSCs to cutaneous repair and their clinical potential in cell-based therapies.

  2. Epidermal Th22 and Tc17 Cells Form a Localized Disease Memory in Clinically Healed Psoriasis

    OpenAIRE

    Cheuk, Stanley; Wikén, Maria; Blomqvist, Lennart; Nylén, Susanne; Talme, Toomas; Ståhle, Mona; Eidsmo, Liv

    2014-01-01

    Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (TRM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartmen...

  3. Adipose-derived Stromal Cells Overexpressing Vascular Endothelial Growth Factor Accelerate Mouse Excisional Wound Healing

    OpenAIRE

    Nauta, Allison; Seidel, Catharina; Deveza, Lorenzo; Montoro, Daniel; Grova, Monica; Ko, Sae Hee; Hyun, Jeong; Geoffrey C Gurtner; Longaker, Michael T.; Yang, Fan

    2012-01-01

    Angiogenesis is essential to wound repair, and vascular endothelial growth factor (VEGF) is a potent factor to stimulate angiogenesis. Here, we examine the potential of VEGF-overexpressing adipose-derived stromal cells (ASCs) for accelerating wound healing using nonviral, biodegradable polymeric vectors. Mouse ASCs were transfected with DNA plasmid encoding VEGF or green fluorescent protein (GFP) using biodegradable poly (β-amino) esters (PBAE). Cells transfected using Lipofectamine 2000, a c...

  4. Intracranial Atherosclerotic Disease

    Directory of Open Access Journals (Sweden)

    Maria Khan

    2011-01-01

    Full Text Available Intracranial atherosclerotic disease (ICAD is the most common proximate mechanism of ischemic stroke worldwide. Approximately half of those affected are Asians. For diagnosis of ICAD, intra-arterial angiography is the gold standard to identify extent of stenosis. However, noninvasive techniques including transcranial ultrasound and MRA are now emerging as reliable modalities to exclude moderate to severe (50%–99% stenosis. Little is known about measures for primary prevention of the disease. In terms of secondary prevention of stroke due to intracranial atherosclerotic stenosis, aspirin continues to be the preferred antiplatelet agent although clopidogrel along with aspirin has shown promise in the acute phase. Among Asians, cilostazol has shown a favorable effect on symptomatic stenosis and is of benefit in terms of fewer bleeds. Moreover, aggressive risk factor management alone and in combination with dual antiplatelets been shown to be most effective in this group of patients. Interventional trials on intracranial atherosclerotic stenosis have so far only been carried out among Caucasians and have not yielded consistent results. Since the Asian population is known to be preferentially effected, focused trials need to be performed to establish treatment modalities that are most effective in this population.

  5. The Anti-Atherosclerotic Effect of Naringin Is Associated with Reduced Expressions of Cell Adhesion Molecules and Chemokines through NF-κB Pathway.

    Science.gov (United States)

    Hsueh, Tun-Pin; Sheen, Jer-Ming; Pang, Jong-Hwei S; Bi, Kuo-Wei; Huang, Chao-Chun; Wu, Hsiao-Ting; Huang, Sheng-Teng

    2016-01-01

    Naringin has been reported to have an anti-atherosclerosis effect but the underlying mechanism is not fully understood. The aim of this study is to investigate the impact of naringin on the TNF-α-induced expressions of cell adhesion molecules, chemokines and NF-κB signaling pathway in human umbilical vein endothelial cells (HUVECs). The experiments revealed that naringin, at concentrations without cytotoxicity, dose-dependently inhibited the adhesion of THP-1 monocytes to the TNF-α-stimulated HUVECs. The TNF-α-induced expressions of cell adhesion molecules, including VCAM-1, ICAM-1 and E-selectin, at both the mRNA and protein levels, were significantly suppressed by naringin in a dose dependent manner. In addition, the TNF-α-induced mRNA and protein levels of chemokines, including fractalkine/CX3CL1, MCP-1 and RANTES, were also reduced by naringin. Naringin significantly inhibited TNF-α-induced nuclear translocation of NF-κB, which resulted from the inhibited phosphorylation of IKKα/β, IκB-α and NF-κB. Altogether, we proposed that naringin modulated TNF-α-induced expressions of cell adhesion molecules and chemokines through the inhibition of TNF-α-induced activation of IKK/NF-κB signaling pathway to exert the anti-atherosclerotic effect. PMID:26861272

  6. The Anti-Atherosclerotic Effect of Naringin Is Associated with Reduced Expressions of Cell Adhesion Molecules and Chemokines through NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Tun-Pin Hsueh

    2016-02-01

    Full Text Available Naringin has been reported to have an anti-atherosclerosis effect but the underlying mechanism is not fully understood. The aim of this study is to investigate the impact of naringin on the TNF-α-induced expressions of cell adhesion molecules, chemokines and NF-κB signaling pathway in human umbilical vein endothelial cells (HUVECs. The experiments revealed that naringin, at concentrations without cytotoxicity, dose-dependently inhibited the adhesion of THP-1 monocytes to the TNF-α-stimulated HUVECs. The TNF-α-induced expressions of cell adhesion molecules, including VCAM-1, ICAM-1 and E-selectin, at both the mRNA and protein levels, were significantly suppressed by naringin in a dose dependent manner. In addition, the TNF-α-induced mRNA and protein levels of chemokines, including fractalkine/CX3CL1, MCP-1 and RANTES, were also reduced by naringin. Naringin significantly inhibited TNF-α-induced nuclear translocation of NF-κB, which resulted from the inhibited phosphorylation of IKKα/β, IκB-α and NF-κB. Altogether, we proposed that naringin modulated TNF-α-induced expressions of cell adhesion molecules and chemokines through the inhibition of TNF-α-induced activation of IKK/NF-κB signaling pathway to exert the anti-atherosclerotic effect.

  7. Self-Healing Conductive Injectable Hydrogels with Antibacterial Activity as Cell Delivery Carrier for Cardiac Cell Therapy.

    Science.gov (United States)

    Dong, Ruonan; Zhao, Xin; Guo, Baolin; Ma, Peter X

    2016-07-13

    Cell therapy is a promising strategy to regenerate cardiac tissue for myocardial infarction. Injectable hydrogels with conductivity and self-healing ability are highly desirable as cell delivery vehicles for cardiac regeneration. Here, we developed self-healable conductive injectable hydrogels based on chitosan-graft-aniline tetramer (CS-AT) and dibenzaldehyde-terminated poly(ethylene glycol) (PEG-DA) as cell delivery vehicles for myocardial infarction. Self-healed electroactive hydrogels were obtained after mixing CS-AT and PEG-DA solutions at physiological conditions. Rapid self-healing behavior was investigated by rheometer. Swelling behavior, morphology, mechanical strength, electrochemistry, conductivity, adhesiveness to host tissue and antibacterial property of the injectable hydrogels were fully studied. Conductivity of the hydrogels is ∼10(-3) S·cm(-1), which is quite close to native cardiac tissue. Proliferation of C2C12 myoblasts in the hydrogel showed its good biocompatibility. After injection, viability of C2C12 cells in the hydrogels showed no significant difference with that before injection. Two different cell types were successfully encapsulated in the hydrogels by self-healing effect. Cell delivery profile of C2C12 myoblasts and H9c2 cardiac cells showed a tunable release rate, and in vivo cell retention in the conductive hydrogels was also studied. Subcutaneous injection and in vivo degradation of the hydrogels demonstrated their injectability and biodegradability. Together, these self-healing conductive biodegradable injectable hydrogels are excellent candidates as cell delivery vehicle for cardiac repair. PMID:27311127

  8. Bioengineered periosteal progenitor cell sheets to enhance tendon-bone healing in a bone tunnel

    Directory of Open Access Journals (Sweden)

    Chih-Hsiang Chang

    2012-12-01

    Full Text Available Background: Tendon-bone tunnel healing is crucial for long term success in anterior cruciate liga­ment (ACL reconstruction. The periosteum contains osteochondral progenitor cells that can differenti­ate into osteoblasts and chondroblasts during tendon-bone healing. We developed a scaf­fold-free method using polymerized fibrin-coated dishes to make functional periosteal progenitor cell (PPC sheets. Bioengineered PPC sheets for enhancing tendon-bone healing were evaluated in an extra-articular bone tunnel model in rabbit. Methods: PPC derived from rabbit tibia periosteum, cultivated on polymerized fi­brin-coated dishes and harvested as PPC sheet. A confocal microscopy assay was used to evaluate the morphology of PPC sheets. PPC sheets as a periosteum to wrap around hamstring tendon grafts were pulled into a 3-mm diameter bone tunnel of tibia, and compared with a tendon graft without PPC sheets treatment. Rabbits were sacrificed at 4 and 8 weeks postoperatively for biochemical as­say and histological assay to demonstrate the enhancement of PPC sheets in tendon-bone healing. Results: PPC spread deposit on fibrin on the dish surface with continuous monolayer PPC was ob­served. Histological staining revealed that PPC sheets enhance collagen and glycosaminoglycans deposi­tion with fibrocartilage formation in the tendon-bone junction at 4 weeks. Collagen fiber with fibrocartilage formation at tendon-bone junction was also found at 8 weeks. Matured fibrocartilage and dense collagen fiber were formed at the tendon-bone interface at 8 weeks by Masson trichrome and Safranin-O staining Conclusions: Periosteal progenitor cell monolayer maintains the differentiated capacity and osteochon­dral potential in order to promote fibrocartilage formation in tendon-bone junction. Bioengi­neered PPC sheets can offer a new feasible therapeutic strategy of a novel approach to en­hance tendon-bone junction healing.

  9. Effect of an Activated Platelet Concentrate on Differentiated Cells Involved in Tissue Healing.

    Science.gov (United States)

    Brini, Anna T; Ceci, Caterina; Taschieri, Silvio; Niada, Stefania; Lolato, Alessandra; Giannasi, Chiara; Mortellaro, Carmen; Del Fabbro, Massimo

    2016-05-01

    Tissue healing is a complex process involving several players such as cells and growth factors released from platelets upon activation. Today, platelet concentrates (PCs) are used in many different medical fields including oral, orthopaedic, and reconstructive surgery since they allow growth factors delivery to the injured site, aiming at enhancing tissue regeneration. The purpose of this in vitro study was to evaluate the effect of the acellular plasma of an activated platelet concentrate obtained using a manual protocol, on the proliferation, and biological activity of differentiated cells involved in tissue healing. Human osteoblasts and dermal fibroblasts were grown in serum-free medium supplemented with PC derived from several donors. Human osteoblast and human dermal fibroblast proliferation was assessed by MTT test after 7 days and cells were count up to 12-day incubation. Human osteoblast osteo-differentiation was tested after 7 and 14-day incubation by alkaline phosphatase assay. The addition of PC to the culture medium caused an increased proliferation with respect to cells grown in standard condition. The results of the present study suggest that PC supports the proliferation of terminally differentiated cells involved in wound healing and tissue regeneration, confirming its beneficial clinical application in regenerative therapies. PMID:27054419

  10. Surgical sutures filled with adipose-derived stem cells promote wound healing.

    Directory of Open Access Journals (Sweden)

    Ann Katharin Reckhenrich

    Full Text Available Delayed wound healing and scar formation are among the most frequent complications after surgical interventions. Although biodegradable surgical sutures present an excellent drug delivery opportunity, their primary function is tissue fixation. Mesenchymal stem cells (MSC act as trophic mediators and are successful in activating biomaterials. Here biodegradable sutures were filled with adipose-derived mesenchymal stem cells (ASC to provide a pro-regenerative environment at the injured site. Results showed that after filling, ASCs attach to the suture material, distribute equally throughout the filaments, and remain viable in the suture. Among a broad panel of cytokines, cell-filled sutures constantly release vascular endothelial growth factor to supernatants. Such conditioned media was evaluated in an in vitro wound healing assay and showed a significant decrease in the open wound area compared to controls. After suturing in an ex vivo wound model, cells remained in the suture and maintained their metabolic activity. Furthermore, cell-filled sutures can be cryopreserved without losing their viability. This study presents an innovative approach to equip surgical sutures with pro-regenerative features and allows the treatment and fixation of wounds in one step, therefore representing a promising tool to promote wound healing after injury.

  11. A role for human skin–resident T cells in wound healing

    OpenAIRE

    Toulon, Antoine; Breton, Lionel; Taylor, Kristen R.; Tenenhaus, Mayer; Bhavsar, Dhaval; Lanigan, Caroline; Rudolph, Ross; Jameson, Julie,; Havran, Wendy L.

    2009-01-01

    Epidermal T cells have been shown to play unique roles in tissue homeostasis and repair in mice through local secretion of distinct growth factors in the skin. Human epidermis contains both αβ+ and γδ+ T cells whose functional capabilities are not understood. We demonstrate that human epidermal T cells are able to produce insulin-like growth factor 1 (IGF-1) upon activation and promote wound healing in a skin organ culture model. Moreover, an analysis of the functional capabilities of T cells...

  12. Methods to study differences in cell mobility during skin wound healing in vitro.

    Science.gov (United States)

    Monsuur, Hanneke N; Boink, Mireille A; Weijers, Ester M; Roffel, Sanne; Breetveld, Melanie; Gefen, Amit; van den Broek, Lenie J; Gibbs, Susan

    2016-05-24

    Wound healing events which occur in humans are difficult to study in animals due to differences in skin physiology. Furthermore there are increasing restrictions in Europe for using animals for testing the therapeutic properties of new compounds. Therefore, in line with the 3Rs (reduction, refinement and replacement of test animals), a number of human in vitro models of different levels of complexity have been developed to investigate cell mobility during wound healing. Keratinocyte, melanocyte, fibroblast and endothelial cell mobility are described, since these are the residential cells which are responsible for restoring the main structural features of the skin. A monolayer scratch assay is used to study random fibroblast and endothelial cell migration in response to EGF and bFGF respectively and a chemotactic assay is used to study directional fibroblast migration towards CCL5. In order to study endothelial sprouting in response to bFGF or VEGF, which involves continuous degradation and resynthesis of a 3D matrix, a fibrin gel is used. Human physiologically relevant tissue-engineered skin models are used to investigate expansion of the stratified, differentiated epidermis (keratinocytes and melanocytes) over a fibroblast populated dermis and also to study migration and distribution of fibroblasts into the dermis. Together these skin models provide a platform for testing the mode of action of novel compounds for enhanced and scar free wound healing. PMID:26903411

  13. Lineage tracing of resident tendon progenitor cells during growth and natural healing.

    Directory of Open Access Journals (Sweden)

    Nathaniel A Dyment

    Full Text Available Unlike during embryogenesis, the identity of tissue resident progenitor cells that contribute to postnatal tendon growth and natural healing is poorly characterized. Therefore, we utilized 1 an inducible Cre driven by alpha smooth muscle actin (SMACreERT2, that identifies mesenchymal progenitors, 2 a constitutively active Cre driven by growth and differentiation factor 5 (GDF5Cre, a critical regulator of joint condensation, in combination with 3 an Ai9 Cre reporter to permanently label SMA9 and GDF5-9 populations and their progeny. In growing mice, SMA9+ cells were found in peritendinous structures and scleraxis-positive (ScxGFP+ cells within the tendon midsubstance and myotendinous junction. The progenitors within the tendon midsubstance were transiently labeled as they displayed a 4-fold expansion from day 2 to day 21 but reduced to baseline levels by day 70. SMA9+ cells were not found within tendon entheses or ligaments in the knee, suggesting a different origin. In contrast to the SMA9 population, GDF5-9+ cells extended from the bone through the enthesis and into a portion of the tendon midsubstance. GDF5-9+ cells were also found throughout the length of the ligaments, indicating a significant variation in the progenitors that contribute to tendons and ligaments. Following tendon injury, SMA9+ paratenon cells were the main contributors to the healing response. SMA9+ cells extended over the defect space at 1 week and differentiated into ScxGFP+ cells at 2 weeks, which coincided with increased collagen signal in the paratenon bridge. Thus, SMA9-labeled cells represent a unique progenitor source that contributes to the tendon midsubstance, paratenon, and myotendinous junction during growth and natural healing, while GDF5 progenitors contribute to tendon enthesis and ligament development. Understanding the mechanisms that regulate the expansion and differentiation of these progenitors may prove crucial to improving future repair strategies.

  14. IL-33-Dependent Group 2 Innate Lymphoid Cells Promote Cutaneous Wound Healing.

    Science.gov (United States)

    Rak, Gregory D; Osborne, Lisa C; Siracusa, Mark C; Kim, Brian S; Wang, Kelvin; Bayat, Ardeshir; Artis, David; Volk, Susan W

    2016-02-01

    Breaches in the skin barrier initiate an inflammatory immune response that is critical for successful wound healing. Innate lymphoid cells (ILCs) are a recently identified population of immune cells that reside at epithelial barrier surfaces such as the skin, lung, and gut, and promote proinflammatory or epithelial repair functions after exposure to allergens, pathogens, or chemical irritants. However, the potential role of ILCs in regulating cutaneous wound healing remains undefined. Here, we demonstrate that cutaneous injury promotes an IL-33-dependent group 2 ILC (ILC2) response and that abrogation of this response impairs re-epithelialization and efficient wound closure. In addition, we provide evidence suggesting that an analogous ILC2 response is operational in acute wounds of human skin. Together, these results indicate that IL-33-responsive ILC2s are an important link between the cutaneous epithelium and the immune system, acting to promote the restoration of skin integrity after injury.

  15. Maggot debridement therapy promotes diabetic foot wound healing by up-regulating endothelial cell activity.

    Science.gov (United States)

    Sun, Xinjuan; Chen, Jin'an; Zhang, Jie; Wang, Wei; Sun, Jinshan; Wang, Aiping

    2016-03-01

    To determine the role of maggot debridement therapy (MDT) on diabetic foot wound healing, we compared growth related factors in wounds before and after treatment. Furthermore, we utilized human umbilical vein endothelial cells (HUVECs) to explore responses to maggot excretions/secretions on markers of angiogenesis and proliferation. The results showed that there was neo-granulation and angiogenesis in diabetic foot wounds after MDT. Moreover, significant elevation in CD34 and CD68 levels was also observed in treated wounds. In vitro, ES increased HUVEC proliferation, improved tube formation, and increased expression of vascular endothelial growth factor receptor 2 in a dose dependent manner. These results demonstrate that MDT and maggot ES can promote diabetic foot wound healing by up-regulating endothelial cell activity.

  16. Reduction of ARNT in myeloid cells causes immune suppression and delayed wound healing

    OpenAIRE

    Scott, Christopher; Bonner, James; Min, Danqing; Boughton, Philip; Stokes, Rebecca; Cha, Kuan Minn; Walters, Stacey N.; Maslowski, Kendle; Sierro, Frederic; Grey, Shane T.; Twigg, Stephen; McLennan, Susan; Gunton, Jenny E.

    2014-01-01

    Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor that binds to partners to mediate responses to environmental signals. To investigate its role in the innate immune system, floxed ARNT mice were bred with lysozyme M-Cre recombinase animals to generate lysozyme M-ARNT (LAR) mice with reduced ARNT expression. Myeloid cells of LAR mice had altered mRNA expression and delayed wound healing. Interestingly, when the animals were rendered diabetic, the difference in wou...

  17. Adult Stem Cell Therapies for Wound Healing: Biomaterials and Computational Models

    OpenAIRE

    Tartarini, Daniele; Mele, Elisa

    2016-01-01

    The increased incidence of diabetes and tumors, associated with global demographic issues (aging and life styles), has pointed out the importance to develop new strategies for the effective management of skin wounds. Individuals affected by these diseases are in fact highly exposed to the risk of delayed healing of the injured tissue that typically leads to a pathological inflammatory state and consequently to chronic wounds. Therapies based on stem cells (SCs) have been proposed for the trea...

  18. A REVIEW OF GENE AND STEM CELL THERAPY IN CUTANEOUS WOUND HEALING

    OpenAIRE

    Branski, Ludwik K.; Gauglitz, Gerd G; Herndon, David N.; Jeschke, Marc G.

    2008-01-01

    Different therapies that modulate wound repair have been proposed over the last few decades. This article reviews the two emerging fields of gene and stem cell therapy in wound healing. Gene therapy, initially developed for treatment of congenital defects, is a new option for enhancing wound repair. In order to accelerate wound closure, genes encoding for growth factors or cytokines have showed the most potential. The majority of gene delivery systems are based on viral transfection, naked DN...

  19. Substance P combined with epidermal stem cells promotes wound healing and nerve regeneration in diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Fei-bin Zhu; Xiang-jing Fang; De-wu Liu; Ying Shao; Hong-yan Zhang; Yan Peng; Qing-ling Zhong; Yong-tie Li; De-ming Liu

    2016-01-01

    Exogenous substance P accelerates wound healing in diabetes, but the mechanism remains poorly understood. Here, we established a rat model by intraperitoneally injecting streptozotocin. Four wounds (1.8 cm diameter) were drilled using a self-made punch onto the back, bilateral to the vertebral column, and then treated using amniotic membrane with epidermal stem cells and/or substance P around and in the middle of the wounds. With the combined treatment the wound-healing rate was 100% at 14 days. With prolonged time, type I col-lagen content gradually increased, yet type III collagen content gradually diminished. Abundant protein gene product 9.5- and substance P-immunoreactive nerve ifbers regenerated. Partial nerve ifber endings extended to the epidermis. The therapeutic effects of combined substance P and epidermal stem cells were better than with amniotic membrane and either factor alone. Our results suggest that the com-bination of substance P and epidermal stem cells effectively contributes to nerve regeneration and wound healing in diabetic rats.

  20. Substance P combined with epidermal stem cells promotes wound healing and nerve regeneration in diabetes mellitus.

    Science.gov (United States)

    Zhu, Fei-Bin; Fang, Xiang-Jing; Liu, De-Wu; Shao, Ying; Zhang, Hong-Yan; Peng, Yan; Zhong, Qing-Ling; Li, Yong-Tie; Liu, De-Ming

    2016-03-01

    Exogenous substance P accelerates wound healing in diabetes, but the mechanism remains poorly understood. Here, we established a rat model by intraperitoneally injecting streptozotocin. Four wounds (1.8 cm diameter) were drilled using a self-made punch onto the back, bilateral to the vertebral column, and then treated using amniotic membrane with epidermal stem cells and/or substance P around and in the middle of the wounds. With the combined treatment the wound-healing rate was 100% at 14 days. With prolonged time, type I collagen content gradually increased, yet type III collagen content gradually diminished. Abundant protein gene product 9.5- and substance P-immunoreactive nerve fibers regenerated. Partial nerve fiber endings extended to the epidermis. The therapeutic effects of combined substance P and epidermal stem cells were better than with amniotic membrane and either factor alone. Our results suggest that the combination of substance P and epidermal stem cells effectively contributes to nerve regeneration and wound healing in diabetic rats.

  1. Polysaccharide hydrogel combined with mesenchymal stem cells promotes the healing of corneal alkali burn in rats.

    Directory of Open Access Journals (Sweden)

    Yifeng Ke

    Full Text Available Corneal chemical burns are common ophthalmic injuries that may result in permanent visual impairment. Although significant advances have been achieved on the treatment of such cases, the structural and functional restoration of a chemical burn-injured cornea remains challenging. The applications of polysaccharide hydrogel and subconjunctival injection of mesenchymal stem cells (MSCs have been reported to promote the healing of corneal wounds. In this study, polysaccharide was extracted from Hardy Orchid and mesenchymal stem cells (MSCs were derived from Sprague-Dawley rats. Supplementation of the polysaccharide significantly enhanced the migration rate of primarily cultured rat corneal epithelial cells. We examined the therapeutic effects of polysaccharide in conjunction with MSCs application on the healing of corneal alkali burns in rats. Compared with either treatment alone, the combination strategy resulted in significantly better recovery of corneal epithelium and reduction in inflammation, neovascularization and opacity of healed cornea. Polysaccharide and MSCs acted additively to increase the expression of anti-inflammatory cytokine (TGF-β, antiangiogenic cytokine (TSP-1 and decrease those promoting inflammation (TNF-α, chemotaxis (MIP-1α and MCP-1 and angiogenesis (VEGF and MMP-2. This study provided evidence that Hardy Orchid derived polysaccharide and MSCs are safe and effective treatments for corneal alkali burns and that their benefits are additive when used in combination. We concluded that combination therapy with polysaccharide and MSCs is a promising clinical treatment for corneal alkali burns and may be applicable for other types of corneal disorder.

  2. Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerates cutaneous wound healing.

    Directory of Open Access Journals (Sweden)

    Katsunari Makino

    Full Text Available Endothelin (ET-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF-α and connective tissue growth factor (CTGF were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach.

  3. Gr-1⁺CD11b⁺ immature myeloid cells (IMC) promote resistance of pro-inflammatory T cells to suppression by regulatory T cells in atherosclerotic Apo E- deficient mice.

    Science.gov (United States)

    Chen, Yulin; Jian, Ying; Liu, Minjie; Zhong, Liang; Zhang, Fang; Yang, Weifeng; Xu, Zhao; Chen, Guofan; Liu, Yuhua

    2014-01-01

    Accumulating evidence indicates that both defects in Treg numbers and/or function as well as resistance of effector T cells to suppression may contribute to the development of human chronic inflammatory diseases. However, which mechanism involved in the progression of atherosclerosis remains unclear. In this study, we evaluated the production and function of CD4⁺ inflammatory and regulatory T cells in atherosclerosis-prone mice. We found that the hyperactivity and unresponsiveness to Treg-mediated suppression of inflammatory CD4⁺ T cells occurred in the progression of atherosclerosis, though Treg cells were present in very large numbers and fully functional. We further found that Gr-1⁺CD11b⁺ immature myeloid cells were significantly accumulated in atherosclerotic Apo E⁻/⁻ mice, and they promoted resistance of inflammatory CD4⁺ T cells to Treg-mediated suppression in vitro and in vivo. we further confirmed that Gr-1⁺CD11b⁺ immature myeloid cells produced high level of interleukin 6 which was at least partially responsible for inducing unresponsiveness of inflammatory CD4⁺ T cells to suppression via activation of Jak/Stat signaling pathway. Taken together, these findings might provide new insights to explore potential targets for immune therapeutic intervention in atherosclerosis.

  4. Nuclear Molecular Imaging for Vulnerable Atherosclerotic Plaques

    OpenAIRE

    Lee, Soo Jin; Paeng, Jin Chul

    2015-01-01

    Atherosclerosis is an inflammatory disease as well as a lipid disorder. Atherosclerotic plaque formed in vessel walls may cause ischemia, and the rupture of vulnerable plaque may result in fatal events, like myocardial infarction or stroke. Because morphological imaging has limitations in diagnosing vulnerable plaque, molecular imaging has been developed, in particular, the use of nuclear imaging probes. Molecular imaging targets various aspects of vulnerable plaque, such as inflammatory cell...

  5. Estimating the wound healing ability of bioactive milk proteins using an optimized cell based assay

    DEFF Research Database (Denmark)

    Nyegaard, Steffen; Andreasen, Trine; Rasmussen, Jan Trige

    oxidoreductase along with minor whey constituents like osteopontin, EPV20 etc. The enterocyte migration rate is a key parameter in maintaining intestinal homeostasis and intestinal repair when recovering from infection or intestinal diseases like Crohns and ulcerative colitis. We developed a novel in vitro wound...... healing assay to determine the bioactive effects of various milk proteins using human small intestine cells grown on extracellular matrix. Silicone inserts are placed in a 96-well plate and enterocytes seeded around it, creating a monolayer with a cell free area. In current ongoing experiments, various...

  6. The Paratenon Contributes to Scleraxis-Expressing Cells during Patellar Tendon Healing

    Science.gov (United States)

    Dyment, Nathaniel A.; Liu, Chia-Feng; Kazemi, Namdar; Aschbacher-Smith, Lindsey E.; Kenter, Keith; Breidenbach, Andrew P.; Shearn, Jason T.; Wylie, Christopher; Rowe, David W.; Butler, David L.

    2013-01-01

    The origin of cells that contribute to tendon healing, specifically extrinsic epitenon/paratenon cells vs. internal tendon fibroblasts, is still debated. The purpose of this study is to determine the location and phenotype of cells that contribute to healing of a central patellar tendon defect injury in the mouse. Normal adult patellar tendon consists of scleraxis-expressing (Scx) tendon fibroblasts situated among aligned collagen fibrils. The tendon body is surrounded by paratenon, which consists of a thin layer of cells that do not express Scx and collagen fibers oriented circumferentially around the tendon. At 3 days following injury, the paratenon thickens as cells within the paratenon proliferate and begin producing tenascin-C and fibromodulin. These cells migrate toward the defect site and express scleraxis and smooth muscle actin alpha by day 7. The thickened paratenon tissue eventually bridges the tendon defect by day 14. Similarly, cells within the periphery of the adjacent tendon struts express these markers and become disorganized. Cells within the defect region show increased expression of fibrillar collagens (Col1a1 and Col3a1) but decreased expression of tenogenic transcription factors (scleraxis and mohawk homeobox) and collagen assembly genes (fibromodulin and decorin). By contrast, early growth response 1 and 2 are upregulated in these tissues along with tenascin-C. These results suggest that paratenon cells, which normally do not express Scx, respond to injury by turning on Scx and assembling matrix to bridge the defect. Future studies are needed to determine the signaling pathways that drive these cells and whether they are capable of producing a functional tendon matrix. Understanding this process may guide tissue engineering strategies in the future by stimulating these cells to improve tendon repair. PMID:23555841

  7. The paratenon contributes to scleraxis-expressing cells during patellar tendon healing.

    Directory of Open Access Journals (Sweden)

    Nathaniel A Dyment

    Full Text Available The origin of cells that contribute to tendon healing, specifically extrinsic epitenon/paratenon cells vs. internal tendon fibroblasts, is still debated. The purpose of this study is to determine the location and phenotype of cells that contribute to healing of a central patellar tendon defect injury in the mouse. Normal adult patellar tendon consists of scleraxis-expressing (Scx tendon fibroblasts situated among aligned collagen fibrils. The tendon body is surrounded by paratenon, which consists of a thin layer of cells that do not express Scx and collagen fibers oriented circumferentially around the tendon. At 3 days following injury, the paratenon thickens as cells within the paratenon proliferate and begin producing tenascin-C and fibromodulin. These cells migrate toward the defect site and express scleraxis and smooth muscle actin alpha by day 7. The thickened paratenon tissue eventually bridges the tendon defect by day 14. Similarly, cells within the periphery of the adjacent tendon struts express these markers and become disorganized. Cells within the defect region show increased expression of fibrillar collagens (Col1a1 and Col3a1 but decreased expression of tenogenic transcription factors (scleraxis and mohawk homeobox and collagen assembly genes (fibromodulin and decorin. By contrast, early growth response 1 and 2 are upregulated in these tissues along with tenascin-C. These results suggest that paratenon cells, which normally do not express Scx, respond to injury by turning on Scx and assembling matrix to bridge the defect. Future studies are needed to determine the signaling pathways that drive these cells and whether they are capable of producing a functional tendon matrix. Understanding this process may guide tissue engineering strategies in the future by stimulating these cells to improve tendon repair.

  8. Diabetes impairs adipose tissue-derived stem cell function and efficiency in promoting wound healing.

    Science.gov (United States)

    Cianfarani, Francesca; Toietta, Gabriele; Di Rocco, Giuliana; Cesareo, Eleonora; Zambruno, Giovanna; Odorisio, Teresa

    2013-01-01

    Adipose tissue-derived stem cells (ASCs) are gaining increasing consideration in tissue repair therapeutic application. Recent evidence indicates that ASCs enhance skin repair in animal models of impaired wound healing. To assess the therapeutic activity of autologous vs. allogeneic ASCs in the treatment of diabetic ulcers, we functionally characterized diabetic ASCs and investigated their potential to promote wound healing with respect to nondiabetic ones. Adipose tissue-derived cells from streptozotocin-induced type 1 diabetic mice were analyzed either freshly isolated as stromal vascular fraction (SVF), or following a single passage of culture (ASCs). Diabetic ASCs showed decreased proliferative potential and migration. Expression of surface markers was altered in diabetic SVF and cultured ASCs, with a reduction in stem cell marker-positive cells. ASCs from diabetic mice released lower amounts of hepatocyte growth factor, vascular endothelial growth factor (VEGF)-A, and insulin-like growth factor-1, growth factors playing important roles in skin repair. Accordingly, the supernatant of diabetic ASCs manifested reduced capability to promote keratinocyte and fibroblast proliferation and migration. Therapeutic potential of diabetic SVF administered to wounds of diabetic mice was blunted as compared with cells isolated from nondiabetic mice. Our data indicate that diabetes alters ASC intrinsic properties and impairs their function, thus affecting therapeutic potential in the autologous treatment for diabetic ulcers. PMID:23627689

  9. Effect of LED phototherapy (λ630 +/- 20nm) on mast cells during wound healing in hypothyroid

    Science.gov (United States)

    Paraguassú, Gardênia M.; De Castro, Isabele Cardoso V.; Vasconcelos, Rebeca M.; da Guarda, Milena G.; Rodriguez, Tânia T.; Ramalho, Maria José P.; Pinheiro, Antônio Luiz B.; Ramalho, Luciana Maria P.

    2014-02-01

    Hypothyroidism has been associated with the disruption of the body's metabolism, including the healing process. LED phototherapy has been studied using several healing models, but their effects on mast cells proliferation associated to hypothyroidism remains unknown. The aim of this study was to assess the effect LED (λ630+/-20nm) phototherapy on mast cells proliferation during tissue repair in hypothyroid rats. Under general anesthesia, a standard surgical wound (1cm2) was created on the dorsum of 24 male Wistar rats divided into 4 groups of 6 animals each: EC-Control Euthyroid; ED-Euthyroid+LED; HC-Control Hypothyroid and HD-Hypothyroid+LED. The irradiation started immediately after surgery and was repeated every other day for 7 days, when animals death occurred. Hypothyroidism was induced in rats with propylthiouracil (0.05g/100mL) administered orally for 4 weeks and maintained until the end of the experiment. The specimens removed were processed to wax and stained with toluidine blue for mast cell identification. The mast cell proliferation was significantly higher in HC group than in EC group (Mann Whitney, phypothyroidism, prolonging the inflammatory phase of repair, and the LED light has a biomodulative effect on mast cell population, even when hipothyroidism was present.

  10. Plasma membrane and cytoskeleton dynamics during single-cell wound healing.

    Science.gov (United States)

    Boucher, Eric; Mandato, Craig A

    2015-10-01

    Wounding leads not only to plasma membrane disruption, but also to compromised cytoskeleton structures. This results not only in unwarranted exchanges between the cytosol and extracellular milieu, but also in loss of tensegrity, which may further endanger the cell. Tensegrity can be described as the interplay between the tensile forces generated by the apparent membrane tension, actomyosin contraction, and the cytoskeletal structures resisting those changes (e.g., microtubules). It is responsible for the structural integrity of the cell and for its ability to sense mechanical signals. Recent reviews dealing with single-cell healing mostly focused on the molecular machineries controlling the traffic and fusion of specific vesicles, or their role in different pathologies. In this review, we aim to take a broader view of the different modes of single cell repair, while focussing on the different ways the changes in plasmalemma surface area and composition, plasmalemma tension, and cytoskeletal dynamics may influence and affect single-cell repair. PMID:26209916

  11. The effect of blocking angiogenesis on anterior cruciate ligament healing following stem cell transplantation.

    Science.gov (United States)

    Takayama, Koji; Kawakami, Yohei; Mifune, Yutaka; Matsumoto, Tomoyuki; Tang, Ying; Cummins, James H; Greco, Nick; Kuroda, Ryosuke; Kurosaka, Masahiro; Wang, Bing; Fu, Freddie H; Huard, Johnny

    2015-08-01

    Ruptured human anterior cruciate ligaments (ACL) contain vascular stem cells capable of enhancing the healing of tendon grafts. In the current study we explored the role that neo-angiogenesis plays in ACL healing. ACL-derived CD34+ cells were isolated via Fluorescence Activated Cell Sorting (FACS) from the rupture sites of human ACLs. The cells were then virally transduced to express either vascular endothelial growth factor (VEGF) or soluble FLT-1 (sFLT-1), which is an antagonist of VEGF. We established five groups: CD34+VEGF(100%), where 100% of the cells were transduced with VEGF, CD34+VEGF(25%), where only 25% of the cells were transduced with VEGF, CD34+, CD34+sFLT-1, and a No cells group. The CD34+sFLT1 group had a significant reduction in biomechanical strength compared to the CD34+ group at 4 and 8 weeks; whereas the biomechanical strength of the CD34+VEGF(25%) group was significantly greater than the CD34+ group at week 4; however, no difference was observed by week 8. Immunohistochemical staining demonstrated a significantly lower number of isolectin B4 and hCD31 positive cells, markers associated with angiogenesis, in the CD34+sFLT1 group, and a higher number of isolectin B4 and hCD31 positive cells in the CD34+VEGF(100%) and CD34+VEGF(25%) groups compared to the CD34+ group. Graft maturation was significantly delayed in the CD34+sFLT1 group and accelerated in the CD34+VEGF(25%) group compared to the CD34+ group. In conclusion, blocking VEGF reduced angiogenesis, graft maturation and biomechanical strength following ACL reconstruction. Native expression of VEGF by the CD34+ cells improved tendon graft maturation and biomechanical strength; however, over-expression of VEGF impeded improvements in biomechanical strength.

  12. Human Wharton's jelly stem cells and its conditioned medium enhance healing of excisional and diabetic wounds.

    Science.gov (United States)

    Fong, Chui-Yee; Tam, Kimberley; Cheyyatraivendran, Suganya; Gan, Shu-Uin; Gauthaman, Kalamegam; Armugam, Arunmozhiarasi; Jeyaseelan, Kandiah; Choolani, Mahesh; Biswas, Arijit; Bongso, Ariff

    2014-02-01

    Wound healing is a major problem in diabetic patients and current treatments have met with limited success. We evaluated the treatment of excisional and diabetic wounds using a stem cell isolated from the human umbilical cord Wharton's jelly (hWJSC) that shares unique properties with embryonic and adult mesenchymal stem cells. hWJSCs are non-controversial, available in abundance, hypo-immunogenic, non-tumorigenic, differentiate into keratinocytes, and secrete important molecules for tissue repair. When human skin fibroblasts (CCD) in conventional scratch-wound assays were exposed to hWJSC-conditioned medium (hWJSC-CM) the fibroblasts at the wound edges migrated and completely covered the spaces by day 2 compared to controls. The number of invaded cells, cell viability, total collagen, elastin, and fibronectin levels were significantly greater in the hWJSC-CM treatment arm compared to controls (P diabetic wounds, healing rates were significantly greater compared to controls (P diabetic wounds via differentiation into keratinocytes and release of important molecules.

  13. Mast cell degranulator compound 48-80 promotes atherosclerotic plaque in apolipoprotein E knockout mice with perivascular common carotid collar placement

    Institute of Scientific and Technical Information of China (English)

    TANG Ya-ling; YANG Yong-zong; WANG Shuang; HUANG Tao; TANG Chao-ke; XU Zeng-xiang; SUN Yu-hui

    2009-01-01

    Background Study of the relationship between mast cells and atherosclerosis is mostly dependent on pathological observation and cytology experiments. To investigate the effects of mast cells degranulation on plaque and their possible mechanisms we used apolipoprotein E knockout mice which had been placed perivascular common carotid collar with mast cells degranulator compound 48-80.Methods Forty apolipoprotein E knockout mice were fed a western-type diet and operated on with placement of perivascular right common carotid collar. Four weeks after surgery, the mice were intraperitoneally injected with compound 48-80 (0.5 mg/kg) or D-Hanks every other day for 4 times. The serum lipids and activity of tryptase were measured. Tissue sections were stained with hematoxylin and eosin. Corresponding sections were stained with toluidine blue and immunohistochemically with antibodies against macrophage-specific antigen, α-smooth muscle actin, interleukin-1β and van Willebrand factor. Simultaneously, basic fibroblast growth factor was detected by in situ hybridization and immunofluorescence.Results No pathological change was observed in common carotid non-collar placement but atherogenesis in common carotid collar placement of both groups. There was a significant increase in plaque area ((5.85±0.75)×104 vs (0.86±0.28)×104 μm2, P<0.05), the degree of lumen stenosis ((81±15)% vs (41±12)%, P <0.05), the activity of tryptase in serum ((0.57±0.13) U/L vs (0.36±0.10) U/L, P <0.05), and the percentage of degranulated mast cells ((80.6±17.8)% vs (13.5±4.1)%, P <0.05). The expressions of macrophage-specific antigen, α-smooth muscle actin, interleukin-1β, basic fibroblast growth factor and the density of neovessel in plaque were more in the compound 48-80 group than in the control group.Conclusions Perivascular common carotid collar placement can promote atherosclerotic plaque formation in apolipoprotein E knockout mice. Compound 48-80 increases plaque area and the degree

  14. Amputation of extremity in patients with atherosclerotic gangrene

    Directory of Open Access Journals (Sweden)

    Tsareva Yu.O.

    2011-12-01

    Full Text Available Aim of investigation — to analyze the results of treatment of patients with atherosclerotic gangrene of a limb, to identify the causes of adverse outcomes amputation. Materials and methods: We analyzed the results of examination and treatment of 218 patients with atherosclerotic gangrene of the limb. Good outcome of amputation was considered the primary surgical wound healing of the stump. Suppuration, secondary healing, re-amputation and death we attributed to the adverse results of amputation. Results: The adverse outcomes of amputation due to technical errors in surgery, properly chosen level, inadequate drainage of the wound stump, an unsuccessful operation on the arteries of a limb, inadequate empirical antibiotic therapy, patient's age, functional capabilities of myocardium, the duration of critical ischemia, as well as the lack of psychological adaptation of patients before amputation. Conclusion: To decide the need for amputation in patients with atherosclerotic gangrene follows the assessment of possible vascular reconstructive surgery. In determining the level of amputation is necessary to objectively assess the degree of disruption of regional blood flow using multilevel manometry and laser Dopplerflowmetry. In preparation for amputation should be paid special attention to the correction of rheological and coagulation properties of blood, normalization of the functional state of the myocardium, as well as specialized psychotherapeutic training for timely and adequate psychological adaptation of the patient

  15. Application of Antrodia camphorata Promotes Rat’s Wound Healing In Vivo and Facilitates Fibroblast Cell Proliferation In Vitro

    Directory of Open Access Journals (Sweden)

    Zahra A. Amin

    2015-01-01

    Full Text Available Antrodia camphorata is a parasitic fungus from Taiwan, it has been documented to possess a variety of pharmacological and biological activities. The present study was undertaken to evaluate the potential of Antrodia camphorata ethanol extract to accelerate the rate of wound healing closure and histology of wound area in experimental rats. The safety of Antrodia camphorata was determined in vivo by the acute toxicity test and in vitro by fibroblast cell proliferation assay. The scratch assay was used to evaluate the in vitro wound healing in fibroblast cells and the excision model of wound healing was tested in vivo using four groups of adult Sprague Dawley rats. Our results showed that wound treated with Antrodia camphorata extract and intrasite gel significantly accelerates the rate of wound healing closure than those treated with the vehicle. Wounds dressed with Antrodia camphorata extract showed remarkably less scar width at wound closure and granulation tissue contained less inflammatory cell and more fibroblast compared to wounds treated with the vehicle. Masson’s trichrom stain showed granulation tissue containing more collagen and less inflammatory cell in Antrodia camphorata treated wounds. In conclusion, Antrodia camphorata extract significantly enhanced the rate of the wound enclosure in rats and promotes the in vitro healing through fibroblast cell proliferation.

  16. CONGENITAL SELF HEALING CUTANEOUS LANGERHANS CELL HISTIOCYTOSIS WITH MULTIPLE HYPOPIGMENTED MACULES AFTER RECOVERY IN A NEONATE

    Directory of Open Access Journals (Sweden)

    A. Ramyar

    2008-04-01

    Full Text Available Langerhans cell histiocytosis (LCH is the most common type of childhood histiocytic disorder with an incidence of 0.2 to 1 per 100,000 children under the age of 15 years (1. The clinical picture of LCH varies from single system (S-Sbone or skin disease to multi-system disease (M-S (2. We report a neonate with disseminated papulonodular eruption containing mononuclear CD1a and S100 positive histiocytic cells infiltration at epidermis and underlying dermis. The diagnosis of a congenital self healing Langerhans cell histiocytosis (CSHLCH was made and follow up showed a complete recovery of the eruptions , leaving hypopigmented macules in the sites corresponding to the initial findings.

  17. Irradiation at 660 nm modulates different genes central to wound healing in wounded and diabetic wounded cell models

    Science.gov (United States)

    Houreld, Nicolette N.

    2014-02-01

    Wound healing is a highly orchestrated process and involves a wide variety of cellular components, chemokines and growth factors. Laser irradiation has influenced gene expression and release of various growth factors, cytokines and extracellular matrix proteins involved in wound healing. This study aimed to determine the expression profile of genes involved in wound healing in wounded and diabetic wounded fibroblast cells in response to irradiation at a wavelength of 660 nm. Human skin fibroblast cells (WS1) were irradiated with a diode laser (wavelength 660 nm; fluence 5 J/cm2; power output 100 mW; power density 11 mW/cm2; spot size 9.1 cm2; exposure duration 7 min 35 s). Total RNA was isolated and 1 μg reverse transcribed into cDNA which was used as a template in real-time qualitative polymerase chain reaction (qPCR). Eighty four genes involved in wound healing (extracellular matrix and cell adhesion; inflammatory cytokines and chemokines; growth factors; and signal transduction) were evaluated in wounded and diabetic wounded cell models. Forty eight hours post-irradiation, 6 genes were significantly upregulated and 8 genes were down-regulated in irradiated wounded cells, whereas 1 gene was up-regulated and 33 genes down-regulated in irradiated diabetic wounded cells. Irradiation of stressed fibroblast cells to a wavelength of 660 nm and a fluence of 5 J/cm2 modulated the expression of different genes involved in wound healing in different cell models. Modulation of these genes leads to the effects of laser irradiation seen both in vivo and in vitro, and facilitates the wound healing process.

  18. HGF Accelerates Wound Healing by Promoting the Dedifferentiation of Epidermal Cells through β1-Integrin/ILK Pathway

    Directory of Open Access Journals (Sweden)

    Jin-Feng Li

    2013-01-01

    Full Text Available Skin wound healing is a critical and complex biological process after trauma. This process is activated by signaling pathways of both epithelial and nonepithelial cells, which release a myriad of different cytokines and growth factors. Hepatocyte growth factor (HGF is a cytokine known to play multiple roles during the various stages of wound healing. This study evaluated the benefits of HGF on reepithelialization during wound healing and investigated its mechanisms of action. Gross and histological results showed that HGF significantly accelerated reepithelialization in diabetic (DB rats. HGF increased the expressions of the cell adhesion molecules β1-integrin and the cytoskeleton remodeling protein integrin-linked kinase (ILK in epidermal cells in vivo and in vitro. Silencing of ILK gene expression by RNA interference reduced expression of β1-integrin, ILK, and c-met in epidermal cells, concomitantly decreasing the proliferation and migration ability of epidermal cells. β1-Integrin can be an important maker of poorly differentiated epidermal cells. Therefore, these data demonstrate that epidermal cells become poorly differentiated state and regained some characteristics of epidermal stem cells under the role of HGF after wound. Taken together, the results provide evidence that HGF can accelerate reepithelialization in skin wound healing by dedifferentiation of epidermal cells in a manner related to the β1-integrin/ILK pathway.

  19. Impedance spectroscopy applied to the fast wounding dynamics of an electrical wound-healing assay in mammalian cells

    International Nuclear Information System (INIS)

    Electrical wound-healing assays are often used as a means to study in vitro cell migration and proliferation. In such analysis, a cell monolayer that sits on a small electrode is electrically wounded and its spectral impedance is then continuously measured in order to monitor the healing process. The relatively slow dynamics of the cell healing have been extensively studied, while those of the much faster wounding phase have not yet been investigated. An analysis of the electrical properties of a particular cell type during this phase could give extra information about the changes in the cell membrane due to the application of the wounding current, and could also be useful to optimize the wounding regime for different cell types. The main issue when trying to register information about these dynamics is that the traditional measurement scheme employed in typical wound-healing assays doesn’t allow the simultaneous application of the wounding signal and measurement of the system’s impedance. In this paper, we overcome this limitation by implementing a measurement strategy consisting of cycles of fast alternating low- and high-voltage signals applied on electrodes covered with mammalian cells. This approach is capable of registering the fast impedance changes during the transient regime corresponding to the cell wounding process. Furthermore, these quasi-simultaneous high- and low-voltage measurements can be compared in order to obtain an empirical correlation between both quantities. (paper)

  20. Innovative Self-Healing Seals for Solid Oxide Fuel Cells (SOFC)

    Energy Technology Data Exchange (ETDEWEB)

    Raj Singh

    2012-06-30

    Solid oxide fuel cell (SOFC) technology is critical to several national initiatives. Solid State Energy Conversion Alliance (SECA) addresses the technology needs through its comprehensive programs on SOFC. A reliable and cost-effective seal that works at high temperatures is essential to the long-term performance of the SOFC for 40,000 hours at 800°C. Consequently, seals remain an area of highest priority for the SECA program and its industry teams. An innovative concept based on self-healing glasses was advanced and successfully demonstrated through seal tests for 3000 hours and 300 thermal cycles to minimize internal stresses under both steady state and thermal transients for making reliable seals for the SECA program. The self-healing concept requires glasses with low viscosity at the SOFC operating temperature of 800°C but this requirement may lead to excessive flow of the glass in areas forming the seal. To address this challenge, a modification to glass properties by addition of particulate fillers is pursued in the project. The underlying idea is that a non-reactive ceramic particulate filler is expected to form glass-ceramic composite and increase the seal viscosity thereby increasing the creep resistance of the glass-composite seals under load. The objectives of the program are to select appropriate filler materials for making glass-composite, fabricate glass-composites, measure thermal expansion behaviors, and determine stability of the glass-composites in air and fuel environments of a SOFC. Self-healing glass-YSZ composites are further developed and tested over a longer time periods under conditions typical of the SOFCs to validate the long-term stability up to 2000 hours. The new concepts of glass-composite seals, developed and nurtured in this program, are expected to be cost-effective as these are based on conventional processing approaches and use of the inexpensive materials.

  1. Development of a Porcine Delayed Wound-Healing Model and Its Use in Testing a Novel Cell-Based Therapy

    International Nuclear Information System (INIS)

    Purpose: A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing. Methods and Materials: Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm2 wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs. Results: The single radiation dose produced a significant loss of dermal microvasculature density (75%) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2% improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect. Conclusions: We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.

  2. Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction.

    Science.gov (United States)

    Yang, Wei; Ng, Fu Liang; Chan, Kenneth; Pu, Xiangyuan; Poston, Robin N; Ren, Meixia; An, Weiwei; Zhang, Ruoxin; Wu, Jingchun; Yan, Shunying; Situ, Haiteng; He, Xinjie; Chen, Yequn; Tan, Xuerui; Xiao, Qingzhong; Tucker, Arthur T; Caulfield, Mark J; Ye, Shu

    2016-07-01

    Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD

  3. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts

    Science.gov (United States)

    Hu, Li; Wang, Juan; Zhou, Xin; Xiong, Zehuan; Zhao, Jiajia; Yu, Ran; Huang, Fang; Zhang, Handong; Chen, Lili

    2016-01-01

    Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell migration, proliferation and collagen synthesis in a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1, PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos can be recruited to soft tissue wound area in a mouse skin incision model and significantly accelerated cutaneous wound healing. Histological analysis showed increased collagen I and III production by systemic administration of exosomes in the early stage of wound healing, while in the late stage, exosomes might inhibit collagen expression to reduce scar formation. Collectively, our findings indicate that ASCs-Exos can facilitate cutaneous wound healing via optimizing the characteristics of fibroblasts. Our results provide a new perspective and therapeutic strategy for the use of ASCs-Exos in soft tissue repair. PMID:27615560

  4. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts.

    Science.gov (United States)

    Hu, Li; Wang, Juan; Zhou, Xin; Xiong, Zehuan; Zhao, Jiajia; Yu, Ran; Huang, Fang; Zhang, Handong; Chen, Lili

    2016-01-01

    Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell migration, proliferation and collagen synthesis in a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1, PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos can be recruited to soft tissue wound area in a mouse skin incision model and significantly accelerated cutaneous wound healing. Histological analysis showed increased collagen I and III production by systemic administration of exosomes in the early stage of wound healing, while in the late stage, exosomes might inhibit collagen expression to reduce scar formation. Collectively, our findings indicate that ASCs-Exos can facilitate cutaneous wound healing via optimizing the characteristics of fibroblasts. Our results provide a new perspective and therapeutic strategy for the use of ASCs-Exos in soft tissue repair. PMID:27615560

  5. The effect of spirulina gel on fibroblast cell number after wound healing

    Directory of Open Access Journals (Sweden)

    Fitria Rahmitasari

    2011-12-01

    Full Text Available Background: Wound healing treatment after tooth extraction should be an important consideration due to mouth discomfort and pain. Spirulina (blue green algae consists of C-phycocyanin, b–carotenoids, vitamin E, zinc, some other trace elements and natural phytochemical which are believed to act as antioxidant and takes part in wound healing process. Purpose: The purpose of this study was to examine the effect of spirulina gel on fibroblast cell number after wound healing process. Methods: Twenty eight males guinea pig are devided into four group, 7 guinea pig each. They are control group and treatment group which is given 0%, 3%, 6%, and 12% spirulina gel. After tooth extraction, histopathological evaluation was done to count fibroblast cell. The data was analyzed by One-Way ANOVA and Tukey HSD. Results: The research has proven the relation between the increased growth of fibroblast cell and spirulina gel application. The higher the doses, the more cell growth. Hence, there has been significant different (p < 0.05 among groups. Conclusion: Spirulina gel increases the number of fibroblast in wound after tooth extraction and 12% spirulina gel has the most potential ability.Latar Belakang: Proses penyembuhan luka pasca pencabutan gigi merupakan salah satu hal yang penting karena akan menimbulkan rasa nyeri dan tidak nyaman dalam rongga mulut. Spirulina (Blue green Algae mengandung C-phycocyanin, b-carotenoids, vitamin E, seng, beberapa trace elemen lainnya, dan phytochemical alami yang terbukti dapat berperan sebagai antioksidan dalam proses penyembuhan luka. Tujuan: Tujuan dari penelitian ini adalah untuk mengetahui efek pemberian gel spirulina terhadap jumlah sel fibroblas pada proses penyembuhan luka pasca pencabutan gigi. Metode: Dua puluh delapan ekor guinea pig jantan dibagi dalam 7 kelompok, masing-masing terdiri dari 4 ekor. Kelompok tersebut adalah kelompok kontrol dan kelompok perlakuan yang diberikan gel spirulina dengan konsentrasi 0

  6. Mesenchymal Stromal Cell-Derived PTX3 Promotes Wound Healing via Fibrin Remodeling.

    Science.gov (United States)

    Cappuzzello, Claudia; Doni, Andrea; Dander, Erica; Pasqualini, Fabio; Nebuloni, Manuela; Bottazzi, Barbara; Mantovani, Alberto; Biondi, Andrea; Garlanda, Cecilia; D'Amico, Giovanna

    2016-01-01

    Although mesenchymal stromal cells (MSCs) can promote wound healing in different clinical settings, the underlying mechanism of MSC-mediated tissue repair has yet to be determined. Because a nonredundant role of pentraxin 3 (PTX3) in tissue repair and remodeling has been recently described, here we sought to determine whether MSC-derived PTX3 might play a role in wound healing. Using a murine model of skin repair, we found that Ptx3-deficient (Ptx3(-/-)) MSCs delayed wound closure and reduced granulation tissue formation compared with wt MSCs. At day 2, confocal microscopy revealed a dramatic reduction in green fluorescent protein (GFP)-expressing Ptx3(-/-) MSCs recruited to the wound, where they appeared to be not only poorly organized in bundles but also scattered in the extracellular matrix. These findings were further confirmed by quantitative biochemical analysis of GFP content in wound extracts. Furthermore, Ptx3(-/-) MSC-treated skins displayed increased levels of fibrin and lower levels of D-dimer, suggesting delayed fibrin-rich matrix remodeling compared with control skins. Consistently, both pericellular fibrinolysis and migration through fibrin were found to be severely affected in Ptx3(-/-) MSCs. Overall, our findings identify an essential role of MSC-derived PTX3 in wound repair underscoring the beneficial potential of MSC-based therapy in the management of intractable wounds.

  7. Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis.

    Science.gov (United States)

    Cheuk, Stanley; Wikén, Maria; Blomqvist, Lennart; Nylén, Susanne; Talme, Toomas; Ståhle, Mona; Eidsmo, Liv

    2014-04-01

    Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (TRM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, TRM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain TRM cells with the ability to maintain and potentially drive recurrent disease. Three common and effective therapies, narrowband-UVB treatment and long-term biologic treatment systemically inhibiting TNF-α or IL-12/23 signaling were studied. Epidermal T cells were highly activated in psoriasis and a high proportion of CD8 T cells expressed TRM markers. In resolved psoriasis, a population of cutaneous lymphocyte-associated Ag, CCR6, CD103, and IL-23R expressing epidermal CD8 T cells was highly enriched. Epidermal CD8 T cells expressing the TRM marker CD103 responded to ex vivo stimulation with IL-17A production and epidermal CD4 T cells responded with IL-22 production after as long as 6 y of TNF-α inhibition. Our data suggest that epidermal TRM cells are retained in resolved psoriasis and that these cells are capable of producing cytokines with a critical role in psoriasis pathogenesis. We provide a potential mechanism for a site-specific T cell-driven disease memory in psoriasis. PMID:24610014

  8. Expression of apolipoprotein serum amyloid A mRNA in human atherosclerotic lesions and cultured vascular cells: implications for serum amyloid A function.

    OpenAIRE

    Meek, R L; Urieli-Shoval, S.; Benditt, E. P.

    1994-01-01

    Altered lipoprotein metabolism and vascular injury are considered to be major parts of the pathogenesis of atherosclerotic lesions. Serum amyloid A (SAA) is a family of acute-phase reactants found residing mainly on high density lipoproteins (HDL) in the circulation. Several functions for the SAAs have been proposed that could be important in atherosclerosis. These include involvement in cholesterol metabolism, participation in detoxification, depression of immune responses, and interference ...

  9. The regulatory mechanism of Hsp90α secretion from endothelial cells and its role in angiogenesis during wound healing

    International Nuclear Information System (INIS)

    Research highlights: → Growth factors such as bFGF, VEGF, PDGF and SDF-1 stimulate Hsp90α secretion from endothelial cells. → Secreted Hsp90α localizes on the leading edge of activated endothelial cells. → Secreted Hsp90α promotes angiogenesis in wound healing. -- Abstract: Heat shock protein 90α (Hsp90α) is a ubiquitously expressed molecular chaperone, which is essential for the maintenance of eukaryote homeostasis. Hsp90α can also be secreted extracellularly and is associated with several physiological and pathological processes including wound healing, cancer, infectious diseases and diabetes. Angiogenesis, defined as the sprouting of new blood vessels from pre-existing capillaries via endothelial cell proliferation and migration, commonly occurs in and contributes to the above mentioned processes. However, the secretion of Hsp90α from endothelial cells and also its function in angiogenesis are still unclear. Here we investigated the role of extracellular Hsp90α in angiogenesis using dermal endothelial cells in vitro and a wound healing model in vivo. We find that the secretion of Hsp90α but not Hsp90β is increased in activated endothelial cells with the induction of angiogenic factors and matrix proteins. Secreted Hsp90α localizes on the leading edge of endothelial cells and promotes their angiogenic activities, whereas Hsp90α neutralizing antibodies reverse the effect. Furthermore, using a mouse skin wound healing model in vivo, we demonstrate that extracellular Hsp90α localizes on blood vessels in granulation tissues of wounded skin and promotes angiogenesis during wound healing. Taken together, our study reveals that Hsp90α can be secreted by activated endothelial cells and is a positive regulator of angiogenesis, suggesting the potential application of Hsp90α as a stimulator for wound repair.

  10. The regulatory mechanism of Hsp90{alpha} secretion from endothelial cells and its role in angiogenesis during wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xiaomin [National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing 100084 (China); Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084 (China); Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084 (China); Luo, Yongzhang, E-mail: yluo@tsinghua.edu.cn [National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing 100084 (China); Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084 (China); Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084 (China)

    2010-07-16

    Research highlights: {yields} Growth factors such as bFGF, VEGF, PDGF and SDF-1 stimulate Hsp90{alpha} secretion from endothelial cells. {yields} Secreted Hsp90{alpha} localizes on the leading edge of activated endothelial cells. {yields} Secreted Hsp90{alpha} promotes angiogenesis in wound healing. -- Abstract: Heat shock protein 90{alpha} (Hsp90{alpha}) is a ubiquitously expressed molecular chaperone, which is essential for the maintenance of eukaryote homeostasis. Hsp90{alpha} can also be secreted extracellularly and is associated with several physiological and pathological processes including wound healing, cancer, infectious diseases and diabetes. Angiogenesis, defined as the sprouting of new blood vessels from pre-existing capillaries via endothelial cell proliferation and migration, commonly occurs in and contributes to the above mentioned processes. However, the secretion of Hsp90{alpha} from endothelial cells and also its function in angiogenesis are still unclear. Here we investigated the role of extracellular Hsp90{alpha} in angiogenesis using dermal endothelial cells in vitro and a wound healing model in vivo. We find that the secretion of Hsp90{alpha} but not Hsp90{beta} is increased in activated endothelial cells with the induction of angiogenic factors and matrix proteins. Secreted Hsp90{alpha} localizes on the leading edge of endothelial cells and promotes their angiogenic activities, whereas Hsp90{alpha} neutralizing antibodies reverse the effect. Furthermore, using a mouse skin wound healing model in vivo, we demonstrate that extracellular Hsp90{alpha} localizes on blood vessels in granulation tissues of wounded skin and promotes angiogenesis during wound healing. Taken together, our study reveals that Hsp90{alpha} can be secreted by activated endothelial cells and is a positive regulator of angiogenesis, suggesting the potential application of Hsp90{alpha} as a stimulator for wound repair.

  11. Study of geometric stability and structural integrity of self-healing glass seal system used in solid oxide fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, W.N.; Sun, X.; Khaleel, M.A. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States)

    2011-02-15

    A self-healing glass seal has the potential to restore its mechanical properties upon being reheated to the solid oxide fuel cell (SOFC) stack operating temperature. Such a self-healing feature is desirable for achieving high seal reliability during thermal cycling. Self-healing glass is also characterized by its low mechanical stiffness and high creep rate at SOFC operating temperatures. Therefore, the geometric stability and structural integrity of the glass seal system are critical to its successful application in SOFCs. This paper describes studies of the geometric stability and structural integrity of the self-healing glass seal system and the influence of various interfacial conditions during the operating and cooling-down processes using finite element analyses. For this purpose, the test cell used in the leakage tests for compliant glass seals, conducted at Pacific Northwest National Laboratory (PNNL), was taken as the initial modeling geometry. The effect of the ceramic stopper on the geometric stability of the self-healing glass sealants was studied first. Two interfacial conditions of the ceramic stopper and glass seals, i.e., bonded (strong) or unbonded (weak), were considered. Then the influences of interfacial strengths at various interfaces, i.e., stopper/glass, stopper/PEN, as well as stopper/IC plate, on the geometric stability and reliability of glass during the operating and cooling processes were examined. (author)

  12. Glial cell line-derived neurotrophic factor promotes barrier maturation and wound healing in intestinal epithelial cells in vitro.

    Science.gov (United States)

    Meir, Michael; Flemming, Sven; Burkard, Natalie; Bergauer, Lisa; Metzger, Marco; Germer, Christoph-Thomas; Schlegel, Nicolas

    2015-10-15

    Recent data suggest that neurotrophic factors from the enteric nervous system are involved in intestinal epithelial barrier regulation. In this context the glial cell line-derived neurotrophic factor (GDNF) was shown to affect gut barrier properties in vivo directly or indirectly by largely undefined processes in a model of inflammatory bowel disease (IBD). We further investigated the potential role and mechanisms of GDNF in the regulation of intestinal barrier functions. Immunostaining of human gut specimen showed positive GDNF staining in enteric neuronal plexus and in enterocytes. In Western blots of the intestinal epithelial cell lines Caco2 and HT29B6, significant amounts of GDNF were detected, suggesting that enterocytes represent an additional source of GDNF. Application of recombinant GDNF on Caco2 and HT29B6 cells for 24 h resulted in significant epithelial barrier stabilization in monolayers with immature barrier functions. Wound-healing assays showed a significantly faster closure of the wounded areas after GDNF application. GDNF augmented cAMP levels and led to significant inactivation of p38 MAPK in immature cells. Activation of p38 MAPK signaling by SB-202190 mimicked GDNF-induced barrier maturation, whereas the p38 MAPK activator anisomycin blocked GDNF-induced effects. Increasing cAMP levels had adverse effects on barrier maturation, as revealed by permeability measurements. However, increased cAMP augmented the proliferation rate in Caco2 cells, and GDNF-induced proliferation of epithelial cells was abrogated by the PKA inhibitor H89. Our data show that enterocytes represent an additional source of GDNF synthesis. GDNF contributes to wound healing in a cAMP/PKA-dependent manner and promotes barrier maturation in immature enterocytes cells by inactivation of p38 MAPK signaling.

  13. Glucose Toxic Effects on Granulation Tissue Productive Cells: The Diabetics’ Impaired Healing

    Directory of Open Access Journals (Sweden)

    Jorge Berlanga-Acosta

    2013-01-01

    Full Text Available Type 2 diabetes mellitus is a metabolic noncommunicable disease with an expanding pandemic magnitude. Diabetes predisposes to lower extremities ulceration and impairs the healing process leading to wound chronification. Diabetes also dismantles innate immunity favoring wound infection. Amputation is therefore acknowledged as one of the disease’s complications. Hyperglycemia is the proximal detonator of systemic and local toxic effectors including proinflammation, acute-phase proteins elevation, and spillover of reactive oxygen and nitrogen species. Insulin axis deficiency weakens wounds’ anabolism and predisposes to inflammation. The systemic accumulation of advanced glycation end-products irreversibly impairs the entire physiology from cells-to-organs. These factors in concert hamper fibroblasts and endothelial cells proliferation, migration, homing, secretion, and organization of a productive granulation tissue. Diabetic wound bed may turn chronically inflammed, procatabolic, and an additional source of circulating pro-inflammatory cytokines, establishing a self-perpetuating loop. Diabetic fibroblasts and endothelial cells may bear mitochondrial damages becoming prone to apoptosis, which impairs granulation tissue cellularity and perfusion. Endothelial progenitor cells recruitment and tubulogenesis are also impaired. Failure of wound reepithelialization remains a clinical challenge while it appears to be biologically multifactorial. Ulcer prevention by primary care surveillance, education, and attention programs is of outmost importance to reduce worldwide amputation figures.

  14. Stem Cells on Biomaterials for Synthetic Grafts to Promote Vascular Healing

    Directory of Open Access Journals (Sweden)

    Patrick Babczyk

    2014-01-01

    Full Text Available This review is divided into two interconnected parts, namely a biological and a chemical one. The focus of the first part is on the biological background for constructing tissue-engineered vascular grafts to promote vascular healing. Various cell types, such as embryonic, mesenchymal and induced pluripotent stem cells, progenitor cells and endothelial- and smooth muscle cells will be discussed with respect to their specific markers. The in vitro and in vivo models and their potential to treat vascular diseases are also introduced. The chemical part focuses on strategies using either artificial or natural polymers for scaffold fabrication, including decellularized cardiovascular tissue. An overview will be given on scaffold fabrication including conventional methods and nanotechnologies. Special attention is given to 3D network formation via different chemical and physical cross-linking methods. In particular, electron beam treatment is introduced as a method to combine 3D network formation and surface modification. The review includes recently published scientific data and patents which have been registered within the last decade.

  15. Electrochemical Impedance Spectroscopy to Characterize Inflammatory Atherosclerotic Plaques

    Science.gov (United States)

    Yu, Fei; Dai, Xiaohu; Beebe, Tyler; Hsiai, Tzung

    2011-01-01

    Despite advances in diagnosis and therapy, atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in the Western world. Predicting metabolically active atherosclerotic lesions has remained an unmet clinical need. We hereby developed an electrochemical strategy to characterize the inflammatory states of high-risk atherosclerotic plaques. Using the concentric bipolar microelectrodes, we sought to demonstrate distinct Electrochemical Impedance Spectroscopic (EIS) measurements for unstable atherosclerotic plaques that harbored active lipids and inflammatory cells. Using equivalent circuits to simulate vessel impedance at the electrode-endoluminal tissue interface, we demonstrated specific electric elements to model working and counter electrode interfaces as well as the tissue impedance. Using explants of human coronary, carotid, and femoral arteries at various Stary stages of atherosclerotic lesions (n = 15), we performed endoluminal EIS measurements (n = 147) and validated with histology and immunohistochemistry. We computed the vascular tissue resistance using the equivalent circuit model and normalized the resistance to the lesion-free regions. Tissue resistance was significantly elevated in the oxLDL-rich thin-cap atheromas (1.57±0.40, n = 14, p 0.05). Hence, we demonstrate that the application of EIS strategy was sensitive to detect fibrous cap oxLDL-rich lesions and specific to distinguish oxLDL-absent fibroatheroma. PMID:21959227

  16. Study of Geometric Stability and Structural Integrity of Self-Healing Glass Seal System Used in Solid Oxide Fuel Cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wenning N.; Sun, Xin; Khaleel, Mohammad A.

    2011-02-15

    A self-healing glass seal has the potential of restoring its mechanical properties upon being reheated to SOFC stack operating temperature, even when it has experienced some cooling induced damage/cracking at room temperature. Such a self-healing feature is desirable for achieving high seal reliability during thermal cycling. On the other hand, self-healing glass is also characterized by its low mechanical stiffness and high creep rate at the typical operating temperature of SOFCs. Therefore, geometry stability and structural integrity of the glass seal system becomes critical to its successful application in SOFCs. In this paper, the geometry stability of the self-healing glass and the influence of various interfacial conditions of ceramic stoppers with the PEN, IC, and glass seal on the structural integrity of the glass seal during the operating and cooling down processes are studied using finite element analyses. For this purpose, the test cell used in the leakage tests for compliant glass seals conducted at PNNL is taken as the initial modeling geometry. The effect of the ceramic stopper on the geometry stability of the self-healing glass sealants is studied first. Two interfacial conditions of the ceramic stopper and glass seals, i.e., bonded (strong) or un-bonded (weak), are considered. Then the influences of interfacial strengths at various interfaces, i.e., stopper/glass, stopper/PEN, as well as stopper/IC plate, on the geometry stability and reliability of glass during the operating and cooling processes are examined.

  17. Adult Stem Cell Therapies for Wound Healing: Biomaterials and Computational Models.

    Science.gov (United States)

    Tartarini, Daniele; Mele, Elisa

    2015-01-01

    The increased incidence of diabetes and tumors, associated with global demographic issues (aging and life styles), has pointed out the importance to develop new strategies for the effective management of skin wounds. Individuals affected by these diseases are in fact highly exposed to the risk of delayed healing of the injured tissue that typically leads to a pathological inflammatory state and consequently to chronic wounds. Therapies based on stem cells (SCs) have been proposed for the treatment of these wounds, thanks to the ability of SCs to self-renew and specifically differentiate in response to the target bimolecular environment. Here, we discuss how advanced biomedical devices can be developed by combining SCs with properly engineered biomaterials and computational models. Examples include composite skin substitutes and bioactive dressings with controlled porosity and surface topography for controlling the infiltration and differentiation of the cells. In this scenario, mathematical frameworks for the simulation of cell population growth can provide support for the design of bioconstructs, reducing the need of expensive, time-consuming, and ethically controversial animal experimentation. PMID:26793702

  18. Effect of 660 nm Light-Emitting Diode on the Wound Healing in Fibroblast-Like Cell Lines

    Directory of Open Access Journals (Sweden)

    Myung-Sun Kim

    2015-01-01

    Full Text Available Light in the red to near-infrared (NIR range (630–1000 nm, which is generated using low energy laser or light-emitting diode (LED arrays, was reported to have a range of beneficial biological effects in many injury models. NIR via a LED is a well-accepted therapeutic tool for the treatment of infected, ischemic, and hypoxic wounds as well as other soft tissue injuries in humans and animals. This study examined the effects of exposure to 660 nm red LED light at intensities of 2.5, 5.5, and 8.5 mW/cm2 for 5, 10, and 20 min on wound healing and proliferation in fibroblast-like cells, such as L929 mouse fibroblasts and human gingival fibroblasts (HGF-1. A photo illumination-cell culture system was designed to evaluate the cell proliferation and wound healing of fibroblast-like cells exposed to 600 nm LED light. The cell proliferation was evaluated by MTT assay, and a scratched wound assay was performed to assess the rate of migrating cells and the healing effect. Exposure to the 660 nm red LED resulted in an increase in cell proliferation and migration compared to the control, indicating its potential use as a phototherapeutic agent.

  19. Role of mesenchymal stem cells on cornea wound healing induced by acute alkali burn.

    Directory of Open Access Journals (Sweden)

    Lin Yao

    Full Text Available The aim of this study was to investigate the effects of subconjunctivally administered mesenchymal stem cells (MSCs on corneal wound healing in the acute stage of an alkali burn. A corneal alkali burn model was generated by placing a piece of 3-mm diameter filter paper soaked in NaOH on the right eye of 48 Sprague-Dawley female rats. 24 rats were administered a subconjunctival injection of a suspension of 2×10(6 MSCs in 0.1 ml phosphate-buffered saline (PBS on day 0 and day 3 after the corneal alkali burn. The other 24 rats were administered a subconjunctival injection of an equal amount of PBS as a control. Deficiencies of the corneal epithelium and the area of corneal neovascularization (CNV were evaluated on days 3 and 7 after the corneal alkali burn. Infiltrated CD68(+ cells were detected by immunofluorescence staining. The mRNA expression levels of macrophage inflammatory protein-1 alpha (MIP-1α, tumor necrosis factor-alpha (TNF-α, monocyte chemotactic protein-1 (MCP-1 and vascular endothelial growth factor (VEGF were analyzed using real-time polymerase chain reaction (real-time PCR. In addition, VEGF protein levels were analyzed using an enzyme-linked immunosorbent assay (ELISA. MSCs significantly enhanced the recovery of the corneal epithelium and decreased the CNV area compared with the control group. On day 7, the quantity of infiltrated CD68(+ cells was significantly lower in the MSC group and the mRNA levels of MIP-1α, TNF-α, and VEGF and the protein levels of VEGF were also down-regulated. However, the expression of MCP-1 was not different between the two groups. Our results suggest that subconjunctival injection of MSCs significantly accelerates corneal wound healing, attenuates inflammation and reduces CNV in alkaline-burned corneas; these effects were found to be related to a reduction of infiltrated CD68(+ cells and the down-regulation of MIP-1α, TNF-α and VEGF.

  20. Effects of recombinant human basic fibroblast growth factor on cell proliferation during mandibular fracture healing in rabbits

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the effects of recombinant human basicfibroblast growth factor (rhbFGF) on the cell proliferation during mandibular fracture healing in rabbits.Methods: The complex of rhbFGF and bovine type I collagen was implanted into the mandibular fracture site under periosteum of the animal. The whole mandible was harvested at 7, 14, 28, 56 and 84 days respectively after operation. The expression of proliferating cell nuclear antigen (PCNA) in callus was examined with immunohistochemical staining.Results: PCNA-positive cells in callus in the rhbFGF-treated group on days 7 and 14 were more than that in the control group (P<0.01).Conclusions: It indicates that rhbFGF can stimulate cell proliferation during mandibular fracture healing in rabbits.

  1. Murine models of human wound healing.

    Science.gov (United States)

    Chen, Jerry S; Longaker, Michael T; Gurtner, Geoffrey C

    2013-01-01

    In vivo wound healing experiments remain the most predictive models for studying human wound healing, allowing an accurate representation of the complete wound healing environment including various cell types, environmental cues, and paracrine interactions. Small animals are economical, easy to maintain, and allow researchers to take advantage of the numerous transgenic strains that have been developed to investigate the specific mechanisms involved in wound healing and regeneration. Here we describe three reproducible murine wound healing models that recapitulate the human wound healing process.

  2. Calcium alginate gels as stem cell matrix-making paracrine stem cell activity available for enhanced healing after surgery.

    Directory of Open Access Journals (Sweden)

    Andreas Schmitt

    Full Text Available Regeneration after surgery can be improved by the administration of anabolic growth factors. However, to locally maintain these factors at the site of regeneration is problematic. The aim of this study was to develop a matrix system containing human mesenchymal stem cells (MSCs which can be applied to the surgical site and allows the secretion of endogenous healing factors from the cells. Calcium alginate gels were prepared by a combination of internal and external gelation. The gelling behaviour, mechanical stability, surface adhesive properties and injectability of the gels were investigated. The permeability of the gels for growth factors was analysed using bovine serum albumin and lysozyme as model proteins. Human MSCs were isolated, cultivated and seeded into the alginate gels. Cell viability was determined by AlamarBlue assay and fluorescence microscopy. The release of human VEGF and bFGF from the cells was determined using an enzyme-linked immunoassay. Gels with sufficient mechanical properties were prepared which remained injectable through a syringe and solidified in a sufficient time frame after application. Surface adhesion was improved by the addition of polyethylene glycol 300,000 and hyaluronic acid. Humans MSCs remained viable for the duration of 6 weeks within the gels. Human VEGF and bFGF was found in quantifiable concentrations in cell culture supernatants of gels loaded with MSCs and incubated for a period of 6 weeks. This work shows that calcium alginate gels can function as immobilization matrices for human MSCs.

  3. Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring.

    Science.gov (United States)

    Li, Zhonghua; Wang, Haiqin; Yang, Bo; Sun, Yukai; Huo, Ran

    2015-12-01

    The regeneration of functional skin remains elusive, due to poor engraftment, deficient vascularization, and excessive scar formation. Aiming to overcome these issues, the present study proposed the combination of a three-dimensional graphene foam (GF) scaffold loaded with bone marrow derived mesenchymal stem cells (MSCs) to improve skin wound healing. The GFs demonstrated good biocompatibility and promoted the growth and proliferation of MSCs. Meanwhile, the GFs loaded with MSCs obviously facilitated wound closure in animal model. The dermis formed in the presence of the GF structure loaded with MSCs was thicker and possessed a more complex structure at day 14 post-surgery. The transplanted MSCs correlated with upregulation of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which may lead to neo-vascularization. Additionally, an anti-scarring effect was observed in the presence of the 3D-GF scaffold and MSCs, as evidenced by a downregulation of transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) together with an increase of TGF-β3. Altogether, the GF scaffold could guide the wound healing process with reduced scarring, and the MSCs were crucial to enhance vascularization and provided a better quality neo-skin. The GF scaffold loaded with MSCs possesses necessary bioactive cues to improve wound healing with reduced scarring, which may be of great clinical significance for skin wound healing.

  4. Light-activated photocurrent degradation and self-healing in perovskite solar cells.

    Science.gov (United States)

    Nie, Wanyi; Blancon, Jean-Christophe; Neukirch, Amanda J; Appavoo, Kannatassen; Tsai, Hsinhan; Chhowalla, Manish; Alam, Muhammad A; Sfeir, Matthew Y; Katan, Claudine; Even, Jacky; Tretiak, Sergei; Crochet, Jared J; Gupta, Gautam; Mohite, Aditya D

    2016-01-01

    Solution-processed organometallic perovskite solar cells have emerged as one of the most promising thin-film photovoltaic technology. However, a key challenge is their lack of stability over prolonged solar irradiation. Few studies have investigated the effect of light soaking on hybrid perovskites and have attributed the degradation in the optoelectronic properties to photochemical or field-assisted ion migration. Here we show that the slow photocurrent degradation in thin-film photovoltaic devices is due to the formation of light-activated meta-stable deep-level trap states. However, the devices can self-heal completely by resting them in the dark for <1 min or the degradation can be completely prevented by operating the devices at 0 °C. We investigate several physical mechanisms to explain the microscopic origin for the formation of these trap states, among which the creation of small polaronic states involving localized cooperative lattice strain and molecular orientations emerges as a credible microscopic mechanism requiring further detailed studies.

  5. Light-activated photocurrent degradation and self-healing in perovskite solar cells

    Science.gov (United States)

    Nie, Wanyi; Blancon, Jean-Christophe; Neukirch, Amanda J.; Appavoo, Kannatassen; Tsai, Hsinhan; Chhowalla, Manish; Alam, Muhammad A.; Sfeir, Matthew Y.; Katan, Claudine; Even, Jacky; Tretiak, Sergei; Crochet, Jared J.; Gupta, Gautam; Mohite, Aditya D.

    2016-05-01

    Solution-processed organometallic perovskite solar cells have emerged as one of the most promising thin-film photovoltaic technology. However, a key challenge is their lack of stability over prolonged solar irradiation. Few studies have investigated the effect of light soaking on hybrid perovskites and have attributed the degradation in the optoelectronic properties to photochemical or field-assisted ion migration. Here we show that the slow photocurrent degradation in thin-film photovoltaic devices is due to the formation of light-activated meta-stable deep-level trap states. However, the devices can self-heal completely by resting them in the dark for <1 min or the degradation can be completely prevented by operating the devices at 0 °C. We investigate several physical mechanisms to explain the microscopic origin for the formation of these trap states, among which the creation of small polaronic states involving localized cooperative lattice strain and molecular orientations emerges as a credible microscopic mechanism requiring further detailed studies.

  6. Methods for promoting wound healing and muscle regeneration with the cell signaling protein Nell1

    Energy Technology Data Exchange (ETDEWEB)

    Culiat, Cymbeline T

    2014-11-04

    The present invention provides methods for promoting wound healing and treating muscle atrophy in a mammal in need. The method comprises administering to the mammal a Nell1 protein or a Nell1 nucleic acid molecule.

  7. Identification of periodontal pathogens in atherosclerotic vessels

    DEFF Research Database (Denmark)

    Fiehn, Nils-Erik; Larsen, Tove; Christiansen, Natalia;

    2005-01-01

    Epidemiological studies have shown that periodontitis may be associated with presence of atherosclerosis. DNA from periodontal pathogens has been detected in atherosclerotic lesions, but viable oral bacteria have not yet been isolated from atherosclerotic plaques. The purpose of the present study...... was to determine if viable oral bacteria could be isolated from atherosclerotic lesions and if DNA from periodontal pathogens could be detected by use of polymerase chain reaction (PCR) techniques....

  8. Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhonghua [Department of Burn and Plastic Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Department of Burn and Plastic Surgery, The Fourth People' s Hospital Of Jinan, Jinan 250031 (China); Wang, Haiqin [Department of Obstetrics and Gynecology, The Fifth People' s Hospital Of Jinan, Jinan 250022 (China); Yang, Bo; Sun, Yukai [Department of Burn and Plastic Surgery, The Fourth People' s Hospital Of Jinan, Jinan 250031 (China); Huo, Ran, E-mail: rhuo12@163.com [Department of Burn and Plastic Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China)

    2015-12-01

    The regeneration of functional skin remains elusive, due to poor engraftment, deficient vascularization, and excessive scar formation. Aiming to overcome these issues, the present study proposed the combination of a three-dimensional graphene foam (GF) scaffold loaded with bone marrow derived mesenchymal stem cells (MSCs) to improve skin wound healing. The GFs demonstrated good biocompatibility and promoted the growth and proliferation of MSCs. Meanwhile, the GFs loaded with MSCs obviously facilitated wound closure in animal model. The dermis formed in the presence of the GF structure loaded with MSCs was thicker and possessed a more complex structure at day 14 post-surgery. The transplanted MSCs correlated with upregulation of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which may lead to neo-vascularization. Additionally, an anti-scarring effect was observed in the presence of the 3D-GF scaffold and MSCs, as evidenced by a downregulation of transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) together with an increase of TGF-β3. Altogether, the GF scaffold could guide the wound healing process with reduced scarring, and the MSCs were crucial to enhance vascularization and provided a better quality neo-skin. The GF scaffold loaded with MSCs possesses necessary bioactive cues to improve wound healing with reduced scarring, which may be of great clinical significance for skin wound healing. - Highlights: • The GFs promoted the growth and proliferation of MSCs. • The GFs loaded with MSCs obviously facilitated wound closure in the animal model. • An anti-scarring effect was observed in the presence of 3D-GF scaffold and MSCs. • The GF scaffold loaded with MSCs has great effect on skin wound healing.

  9. Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring

    International Nuclear Information System (INIS)

    The regeneration of functional skin remains elusive, due to poor engraftment, deficient vascularization, and excessive scar formation. Aiming to overcome these issues, the present study proposed the combination of a three-dimensional graphene foam (GF) scaffold loaded with bone marrow derived mesenchymal stem cells (MSCs) to improve skin wound healing. The GFs demonstrated good biocompatibility and promoted the growth and proliferation of MSCs. Meanwhile, the GFs loaded with MSCs obviously facilitated wound closure in animal model. The dermis formed in the presence of the GF structure loaded with MSCs was thicker and possessed a more complex structure at day 14 post-surgery. The transplanted MSCs correlated with upregulation of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which may lead to neo-vascularization. Additionally, an anti-scarring effect was observed in the presence of the 3D-GF scaffold and MSCs, as evidenced by a downregulation of transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) together with an increase of TGF-β3. Altogether, the GF scaffold could guide the wound healing process with reduced scarring, and the MSCs were crucial to enhance vascularization and provided a better quality neo-skin. The GF scaffold loaded with MSCs possesses necessary bioactive cues to improve wound healing with reduced scarring, which may be of great clinical significance for skin wound healing. - Highlights: • The GFs promoted the growth and proliferation of MSCs. • The GFs loaded with MSCs obviously facilitated wound closure in the animal model. • An anti-scarring effect was observed in the presence of 3D-GF scaffold and MSCs. • The GF scaffold loaded with MSCs has great effect on skin wound healing

  10. Fibroblast-like cells differentiated from adipose-derived mesenchymal stem cells for vocal fold wound healing.

    Science.gov (United States)

    Hu, Rong; Ling, Wei; Xu, Wen; Han, Demin

    2014-01-01

    Tissue engineering has revealed the potential to regenerate injured vocal folds, and identification of the most suitable seed cells has remained a hot topic of research. The aim of this study was to implant fibroblast-like cells differentiated from adipose-derived mesenchymal stem cells (ADSCs) in a canine acute vocal fold wound model. We then sought to characterize changes in the extracellular matrix (ECM) proteins of vocal fold lamina propria. For this purpose, ADSCs were induced to differentiate into fibroblasts under the regulation of connective tissue growth factor in vitro. Cell surface proteins were identified by immunofluorescence staining. Thirty vocal folds of 17 canines were injured by localized resection and injected with fibroblast-like cells (differentiated ADSCs, dADSCs), ADSCs or vocal fold fibroblasts (VFFs). The morphology of vocal folds was observed, and the characteristics of ECM protein components (collagen, elastin, hyaluronic acid, decorin and fibronectin) were evaluated by immunofluorescence staining from 15 days to 6 months following implantation. The results showed that in vitro, the dADSCs showed morphology and cell surface protein expression similar to those of VFFs. After implantation in vivo, the surfaces of the recipient vocal folds became almost smooth in the dADSCs and ADSCs groups at 6 months but remained slightly concave and stiff in the VFFs group. The elastin fluorescence intensity increased significantly and was maintained at a high level in the dADSCs group. The collagen fluorescence intensity increased slightly in the dADSCs and ADSCs groups, whereas it demonstrated a more irregular arrangement in the VFFs group. The fluorescence intensity of hyaluronic acid, decorin and fibronectin was similar between the three implanted groups. These results indicated that dADSCs may confer an advantage for vocal fold wound healing. Furthermore, dADSCs have the ability to secrete ECM components in vivo, particularly elastin, which may be

  11. SELECTINS IN CORONARY ATHEROSCLEROTIC DISEASE:A REVIEW

    Institute of Scientific and Technical Information of China (English)

    李远方; 胡健

    2001-01-01

    The development of atherosclerotic lesions appears to be inflammatory in nature. It involves the recruitment of blood monocytes to the vascular endothelium, followed by intimal infiltration. Monocytes differentiate to macrophages, then internalize lipids to form foam cells, thus develop fatty streak lesion. A wide range of adhesion molecules governs these interactions between cells, among these molecules are selectins. Selectins mediate the first step in leukocyte adhesion at sites of inflammation or injury, characterized by rolling and tethering

  12. Transforming growth factor-beta mediates intestinal healing and susceptibility to injury in vitro and in vivo through epithelial cells.

    Science.gov (United States)

    Beck, Paul L; Rosenberg, Ian M; Xavier, Ramnik J; Koh, Theodore; Wong, Josée F; Podolsky, Daniel K

    2003-02-01

    In vitro studies suggest that transforming growth factor (TGF)-beta has potent effects on gastrointestinal mucosal integrity, wound repair, and neoplasia. However, the multiplicity of actions of this peptide on many different cell types confounds efforts to define the role of TGF-beta within the intestinal epithelium in vivo. To delineate these effects selective blockade of intestinal epithelial TGF-beta activity was undertaken through targeted expression of a dominant-negative (DN) TGF-beta RII to intestinal epithelial cells in vitro and in vivo. Stable intestinal epithelial cell (IEC)-6 lines overexpressing TGF-beta RII-DN (nucleotides -7 to 573) were established. Transgenic mice overexpressing TGF-beta RII-DN under the regulation of a modified liver fatty acid-binding promoter (LFABP-PTS4) were constructed. In vitro healing was assessed by wounding of confluent monolayers. Colitis was induced by the addition of dextran sodium sulfate (2.5 to 7.5% w/v) to their drinking water. Overexpression of TGF-beta RII-DN in intestinal epithelial cell-6 cells resulted in a marked reduction in cell migration and TGF-beta-stimulated wound healing in vitro. TGF-beta RII-DN transgenic mice did not exhibit baseline intestinal inflammation or changes in survival, body weight, epithelial cell proliferation, aberrant crypt foci, or tumor formation. TGF-beta RII-DN mice were markedly more susceptible to dextran sodium sulfate-induced colitis and exhibited impaired recovery after colonic injury. TGF-beta is required for intestinal mucosal healing and TGF-beta modulation of the intestinal epithelium plays a central role in determining susceptibility to injury. PMID:12547717

  13. Differential properties of human ACL and MCL stem cells may be responsible for their differential healing capacity

    Directory of Open Access Journals (Sweden)

    Fu Freddie H

    2011-06-01

    Full Text Available Abstract Background The human anterior cruciate ligament (hACL and medial collateral ligament (hMCL of the knee joint are frequently injured, especially in athletic settings. It has been known that, while injuries to the MCL typically heal with conservative treatment, ACL injuries usually do not heal. As adult stem cells repair injured tissues through proliferation and differentiation, we hypothesized that the hACL and hMCL contain stem cells exhibiting unique properties that could be responsible for the differential healing capacity of the two ligaments. Methods To test the above hypothesis, we derived ligament stem cells from normal hACL and hMCL samples from the same adult donors using tissue culture techniques and characterized their properties using immunocytochemistry, RT-PCR, and flow cytometry. Results We found that both hACL stem cells (hACL-SCs and hMCL stem cells (hMCL-SCs formed colonies in culture and expressed stem cell markers nucleostemin and stage-specific embryonic antigen-4 (SSEA-4. Moreover, both hACL-SCs and hMCL-SCs expressed CD surface markers for mesenchymal stem cells, including CD44 and CD90, but not those markers for vascular cells, CD31, CD34, CD45, and CD146. However, hACL-SCs differed from hMCL-SCs in that the size and number of hACL-SC colonies in culture were much smaller and grew more slowly than hMCL-SC colonies. Moreover, fewer hACL-SCs in cell colonies expressed stem cell markers STRO-1 and octamer-binding transcription factor-4 (Oct-4 than hMCL-SCs. Finally, hACL-SCs had less multi-differentiation potential than hMCL-SCs, evidenced by differing extents of adipogenesis, chondrogenesis, and osteogenesis in the respective induction media. Conclusions This study shows for the first time that hACL-SCs are intrinsically different from hMCL-SCs. We suggest that the differences in their properties contribute to the known disparity in healing capabilities between the two ligaments.

  14. Two- and three-dimensional co-culture models of soft tissue healing: pericyte-endothelial cell interaction.

    Science.gov (United States)

    Jennewein, Martina; Bubel, Monika; Guthörl, Silke; Metzger, Wolfgang; Weigert, Martin; Pohlemann, Tim; Oberringer, Martin

    2016-08-01

    The demographic change in western countries towards an older population is being shadowed by an increased appearance of chronic diseases influencing soft tissue healing in a negative manner. Although various promising therapeutic approaches are available for treating chronic wounds, no in vitro model exists that successfully allows the analysis of interacting cells and of the effect of therapeutic drugs within a wound. Granulation tissue assures wound stability, neo-angiogenesis and revascularization finally leading to functional soft tissue repair. As one of the first steps in developing a model for human granulation tissue, we examined microvascular endothelial cells and pericytes in conventional 2D and in 3D spheroid co-cultures. We determined which parameters could be used in a standardized manner and whether the cultures were responsive to hypoxia and to erythropoietin supplementation. The read-out parameters of cell migration, cell density, rate of apoptotic cells, spatial cell distribution in the spheroid and spheroid volume were shown to be excellent analytic measures. In addition, quantification of hypoxia-related genes identified a total of 13 genes that were up-regulated in spheroids after hypoxia. As these parameters delivered reliable results in the present approach and as the general morphological distribution of pericytes and endothelial cells within the spheroid occurred in a typical manner, we believe that this basic in vitro model will serve for the future study of diverse aspects of soft tissue healing. PMID:27026609

  15. Human unrestricted somatic stem cells loaded in nanofibrous PCL scaffold and their healing effect on skin defects.

    Science.gov (United States)

    Bahrami, Hoda; Keshel, Saeed Heidari; Chari, Aliakbar Jafari; Biazar, Esmaeil

    2016-09-01

    Unrestricted somatic stem cells (USSCs) loaded in nanofibrous polycaprolactone (PCL) scaffolds can be used for skin regeneration when grafted onto full-thickness skin defects of rats. Nanofibrous PCL scaffolds were designed by the electrospinning method and crosslinked with laminin protein. Afterwards, the scaffolds were evaluated by scanning electron microscopy, and physical and mechanical assays. In this study, nanofibrous PCL scaffolds loaded with USSCs were grafted onto the skin defects. The wounds were subsequently investigated 21 days after grafting. Results of mechanical and physical analyses showed good resilience and compliance to movement as a skin graft. In animal models; study samples exhibited the most pronounced effect on wound closure, with statistically significant improvement in wound healing being seen at 21 days post-operatively. Histological examinations of healed wounds from all samples showed a thin epidermis plus recovered skin appendages in the dermal layer for samples with cell. Thus, the graft of nanofibrous PCL scaffolds loaded with USSC showed better results during the healing process of skin defects in rat models. PMID:26140614

  16. Mesenchymal Stromal Cells as Cell-Based Therapeutics for Wound Healing

    OpenAIRE

    Samir Malhotra; Hu, Michael S.; Marshall, Clement D.; Tripp Leavitt; Alexander T. M. Cheung; Gonzalez, Jennifer G.; Harleen Kaur; Peter Lorenz, H.; Longaker, Michael T.

    2016-01-01

    Chronic wounds are a source of substantial morbidity for patients and are a major financial burden for the healthcare system. There are no current therapies that reliably improve nonhealing wounds or reverse pathological scarring. Mesenchymal stromal cells (MSCs) are a promising source of novel cell-based therapies due to the ease of their harvest and their integral role in the native wound repair process. Recent work has addressed the problems of loss of plasticity and off-target delivery th...

  17. Boron promotes streptozotocin-induced diabetic wound healing: roles in cell proliferation and migration, growth factor expression, and inflammation.

    Science.gov (United States)

    Demirci, Selami; Doğan, Ayşegül; Aydın, Safa; Dülger, Esra Çikler; Şahin, Fikrettin

    2016-06-01

    Acute wounds do not generally require professional treatment modalities and heal in a predictable fashion, but chronic wounds are mainly accompanied with infection and prolonged inflammation, leading to healing impairments and continuous tissue degradation. Although a vast amount of products have been introduced in the market, claiming to provide a better optimization of local and systemic conditions of patients, they do not meet the expectations due to being expensive and not easily accessible, requiring wound care facilities, having patient-specific response, low efficiency, and severe side-effects. In this sense, developing new, safe, self-applicable, effective, and cheap wound care products with broad-range antimicrobial activity is still an attractive area of international research. In the present work, boron derivatives [boric acid and sodium pentaborate pentahydrate (NaB)] were evaluated for their antimicrobial activity, proliferation, migratory, angiogenesis, gene, and growth factor expression promoting effects on dermal cells in vitro. In addition, boron-containing hydrogel formulation was examined for its wound healing promoting potential using full-thickness wound model in streptozotocin-induced diabetic rats. The results revealed that while both boron compounds significantly increased proliferation, migration, vital growth factor, and gene expression levels of dermal cells along with displaying remarkable antimicrobial effects against bacteria, yeast, and fungi, NaB displayed greater antimicrobial properties as well as gene and growth factor expression inductive effects. Animal studies proved that NaB-containing gel formulation enhanced wound healing rate of diabetic animals and histopathological scores. Overall data suggest a potential promising therapeutic option for the management of chronic wounds but further studies are highly warranted to determine signaling pathways and target metabolisms in which boron is involved to elucidate the limitations

  18. Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Christian Hafner; Stefanie Meyer; Ilja Hagen; Bernd Becker; Alexander Roesch; Michael Landthaler; Thomas Vogt

    2005-01-01

    AIM: Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells.METHODS: Upon stimulation of ephrin-B pathways in IFC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix(R) rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase (FAK) activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy.RESULTS: Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes.Furthermore, we show that the expression of repairrelated genes is also accompanied by activation of the ERK1/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution.CONCLUSION: Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.

  19. Identification of periodontal pathogens in atherosclerotic vessels

    DEFF Research Database (Denmark)

    Fiehn, Nils-Erik; Larsen, Tove; Christiansen, Natalia;

    2005-01-01

    Epidemiological studies have shown that periodontitis may be associated with presence of atherosclerosis. DNA from periodontal pathogens has been detected in atherosclerotic lesions, but viable oral bacteria have not yet been isolated from atherosclerotic plaques. The purpose of the present study...

  20. Imaging Atherosclerotic Plaque Calcification: Translating Biology.

    Science.gov (United States)

    Bailey, Grant; Meadows, Judith; Morrison, Alan R

    2016-08-01

    Calcification of atherosclerotic lesions was long thought to be an age - related, passive process, but increasingly data has revealed that atherosclerotic calcification is a more active process, involving complex signaling pathways and bone-like genetic programs. Initially, imaging of atherosclerotic calcification was limited to gross assessment of calcium burden, which is associated with total atherosclerotic burden and risk of cardiovascular mortality and of all cause mortality. More recently, sophisticated molecular imaging studies of the various processes involved in calcification have begun to elucidate information about plaque calcium composition and consequent vulnerability to rupture, leading to hard cardiovascular events like myocardial infarction. As such, there has been renewed interest in imaging calcification to advance risk assessment accuracy in an evolving era of precision medicine. Here we summarize recent advances in our understanding of the biologic process of atherosclerotic calcification as well as some of the molecular imaging tools used to assess it. PMID:27339750

  1. Enhanced healing of diabetic wounds by topical administration of adipose tissue-derived stromal cells overexpressing stromal-derived factor-1: biodistribution and engraftment analysis by bioluminescent imaging.

    Science.gov (United States)

    Di Rocco, Giuliana; Gentile, Antonietta; Antonini, Annalisa; Ceradini, Francesca; Wu, Joseph C; Capogrossi, Maurizio C; Toietta, Gabriele

    2010-01-01

    Chronic ulcers represent a major health problem in diabetic patients resulting in pain and discomfort. Conventional therapy does not guarantee adequate wound repair. In diabetes, impaired healing is partly due to poor endothelial progenitor cells mobilisation and homing, with altered levels of the chemokine stromal-derived factor-1 (SDF-1) at the wound site. Adipose tissue-associated stromal cells (AT-SCs) can provide an accessible source of progenitor cells secreting proangiogenic factors and differentiating into endothelial-like cells. We demonstrated that topical administration of AT-SCs genetically modified ex vivo to overexpress SDF-1, promotes wound healing into diabetic mice. In particular, by in vivo bioluminescent imaging analysis, we monitored biodistribution and survival after transplantation of luciferase-expressing cells. In conclusion, this study indicates the therapeutic potential of AT-SCs administration in wound healing, through cell differentiation, enhanced cellular recruitment at the wound site, and paracrine effects associated with local growth-factors production. PMID:21234108

  2. A gene expression programme induced by bovine colostrum whey promotes growth and wound-healing processes in intestinal epithelial cells.

    Science.gov (United States)

    Blais, M; Pouliot, Y; Gauthier, S; Boutin, Y; Lessard, M

    2014-01-01

    Bovine colostrum is well known for its beneficial properties on health and development. It contains a wide variety of bioactive ingredients that are known to promote a number of cellular processes. Therefore the use of colostrum whey as a feed additive to promote intestinal health has been proposed, yet little is known about mechanisms implicated in its beneficial properties on intestinal epithelial cells. In the present paper, casein were removed from bovine colostrum and the remaining liquid, rich in bioactive compounds, was evaluated for its capacity to modulate cellular processes in porcine intestinal epithelial cell line IPEC-J2 and human colon adenocarcinoma cell line Caco-2/15. First, we verified the effect of colostrum whey and cheese whey on processes involved in intestinal wound healing, including cell proliferation, attachment, morphology and migration. Our results showed that colostrum whey promoted proliferation and migration, and decreased specifically the attachment of Caco-2/15 cells on the culture dish. On the other hand, cheese whey induced proliferation and morphological changes in IPEC-J2 cells, but failed to induce migration. The gene expression profile of IPEC-J2 cells following colostrum whey treatment was evaluated by microarray analysis. Results revealed that the expression of a significant number of genes involved in cell migration, adhesion and proliferation was indeed affected in colostrum whey-treated cells. In conclusion, colostrum specific bioactive content could be beneficial for intestinal epithelial cell homoeostasis by controlling biological processes implicated in wound healing through a precise gene expression programme. PMID:26101625

  3. Macrophage p53 controls macrophage death in atherosclerotic lesions of apolipoprotein E deficient mice

    NARCIS (Netherlands)

    Boesten, L.S.M.; Zadelaar, A.S.M.; Nieuwkoop, A. van; Hu, L.; Teunisse, A.F.A.S.; Jochemsen, A.G.; Evers, B.; Water, B. van de; Gijbels, M.J.J.; Vlijmen, B.J.M. van; Havekes, L.M.; Winther, M.P.J. de

    2009-01-01

    The cellular composition of atherosclerotic lesions is determined by many factors including cell infiltration, proliferation and cell death. Tumor suppressor gene p53 has been shown to regulate both cell proliferation and cell death in many cell types. In the present study, we investigated the role

  4. Acute and chronic wound fluids inversely influence adipose-derived stem cell function: molecular insights into impaired wound healing.

    Science.gov (United States)

    Koenen, Paola; Spanholtz, Timo A; Maegele, Marc; Stürmer, Ewa; Brockamp, Thomas; Neugebauer, Edmund; Thamm, Oliver C

    2015-02-01

    Wound healing is a complex biological process that requires a well-orchestrated interaction of mediators as well as resident and infiltrating cells. In this context, mesenchymal stem cells play a crucial role as they are attracted to the wound site and influence tissue regeneration by various mechanisms. In chronic wounds, these processes are disturbed. In a comparative approach, adipose-derived stem cells (ASC) were treated with acute and chronic wound fluids (AWF and CWF, respectively). Proliferation and migration were investigated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and transwell migration assay. Gene expression changes were analysed using quantitative real time-polymerase chain reaction. AWF had a significantly stronger chemotactic impact on ASC than CWF (77·5% versus 59·8% migrated cells). While proliferation was stimulated by AWF up to 136·3%, CWF had a negative effect on proliferation over time (80·3%). Expression of b-FGF, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 was strongly induced by CWF compared with a mild induction by AWF. These results give an insight into impaired ASC function in chronic wounds. The detected effect of CWF on proliferation and migration of ASC might be one reason for an insufficient healing process in chronic wounds.

  5. Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF) Factor on Corneal Epithelial Cells in Corneal Wound Healing Model

    OpenAIRE

    Chang Rae Rho; Mi-young Park; Seungbum Kang

    2015-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs). We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF). An in vitro migration assay was performed to investigate the migration rate of HCECs ...

  6. Human urotensin II promotes hypertension and atherosclerotic cardiovascular diseases.

    Science.gov (United States)

    Watanabe, Takuya; Arita, Shigeko; Shiraishi, Yuji; Suguro, Toshiaki; Sakai, Tetsuo; Hongo, Shigeki; Miyazaki, Akira

    2009-01-01

    Human urotensin II (U-II), the most potent vasoconstrictor undecapeptide identified to date, and its receptor (UT) are involved in the pathogenesis of systemic and pulmonary hypertension. Here, we review recent advances in our understanding of the pathophysiology of U-II with particular reference to its role in atherosclerotic cardiovascular diseases. Single-nucleotide polymorphisms of U-II gene (S89N) are associated with onset of essential hypertension, type II diabetes mellitus, and insulin resistance in the Asian population. Plasma U-II levels are elevated in patients with vascular endothelial dysfunction-related diseases such as essential hypertension, diabetes mellitus, atherosclerosis, ischemic heart disease, and heart failure. Chronic infusion of U-II enhances atherosclerotic lesions in the aorta in apolipoprotein E-knockout mice. In human atherosclerotic plaques from the aorta and coronary and carotid arteries, U-II is expressed at high levels in endothelial cells (ECs) and lymphocytes, whereas UT is expressed at high levels in vascular smooth muscle cells (VSMCs), ECs, monocytes, and macrophages. U-II stimulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in human ECs as chemoattractant for monocytes, and accelerates foam cell formation by up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages. U-II produces reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate oxidase activation in human VSMCs, and stimulates VSMC proliferation with synergistic effects when combined with ROS, oxidized LDL, and serotonin. Clinical studies demonstrated increased plasma U-II levels in accordance with the severity of carotid atherosclerosis in patients with essential hypertension and that of coronary artery lesions in patients with ischemic heart disease. Here, we summarize the key roles of U-II in progression of hypertension and atherosclerotic cardiovascular diseases

  7. The anti-motility signaling mechanism of TGFβ3 that controls cell traffic during skin wound healing

    Directory of Open Access Journals (Sweden)

    Arum Han

    2012-09-01

    When skin is wounded, migration of epidermal keratinocytes at the wound edge initiates within hours, whereas migration of dermal fibroblasts toward the wounded area remains undetectable until several days later. This “cell type traffic” regulation ensures proper healing of the wound, as disruptions of the regulation could either cause delay of wound healing or result in hypertrophic scars. TGFβ3 is the critical traffic controller that selectively halts migration of the dermal, but not epidermal, cells to ensure completion of wound re-epithelialization prior to wound remodeling. However, the mechanism of TGFβ3's anti-motility signaling has never been investigated. We report here that activated TβRII transmits the anti-motility signal of TGFβ3 in full to TβRI, since expression of the constitutively activated TβRI-TD mutant was sufficient to replace TGFβ3 to block PDGF-bb-induced dermal fibroblast migration. Second, the three components of R-Smad complex are all required. Individual downregulation of Smad2, Smad3 or Smad4 prevented TGFβ3 from inhibiting dermal fibroblast migration. Third, Protein Kinase Array allowed us to identify the protein kinase A (PKA as a specific downstream effector of R-Smads in dermal fibroblasts. Activation of PKA alone blocked PDGF-bb-induced dermal fibroblast migration, just like TGFβ3. Downregulation of PKA's catalytic subunit nullified the anti-motility signaling of TGFβ3. This is the first report on anti-motility signaling mechanism by TGFβ family cytokines. Significance of this finding is not only limited to wound healing but also to other human disorders, such as heart attack and cancer, where the diseased cells have often managed to avoid the anti-motility effect of TGFβ.

  8. Normalization of wound healing and stem cell marker patterns in organ-cultured human diabetic corneas by gene therapy of limbal cells.

    Science.gov (United States)

    Saghizadeh, Mehrnoosh; Dib, Christian M; Brunken, William J; Ljubimov, Alexander V

    2014-12-01

    Overexpression of c-met and suppression of matrix metalloproteinase-10 (MMP-10) and cathepsin F genes was previously shown to normalize wound healing, epithelial and stem cell marker patterns in organ-cultured human diabetic corneas. We now examined if gene therapy of limbal cells only would produce similar effects. Eight pairs of organ-cultured autopsy human diabetic corneas were used. One cornea of each pair was treated for 48 h with adenoviruses (Ad) harboring full-length c-met mRNA or a mixture (combo) of Ad with c-met and shRNA to MMP-10 and cathepsin F genes. Medium was kept at the limbal level to avoid transduction of central corneal epithelium. Fellow corneas received control Ad with EGFP gene. After additional 5 (c-met) or 10 days (combo) incubation, central corneal epithelial debridement with n-heptanol was performed, and wound healing times were determined microscopically. Corneal cryostat sections were immunostained for diabetic and putative limbal stem cell markers, α3β1 integrin, nidogen-1, fibronectin, laminin γ3 chain, ΔNp63α, keratins 14, 15, and 17, as well as for activated signaling intermediates, phosphorylated EGFR, Akt, and p38. Limbal c-met overexpression significantly accelerated healing of 8.5-mm epithelial wounds over EGFP controls (6.3 days vs. 9.5 days, p treatment produced a similar result (6.75 days vs. 13.5 days, p stem cell compartment has a beneficial effect on the diabetic corneal wound healing and on diabetic and stem cell marker expression, and shows potential for alleviating symptoms of diabetic keratopathy.

  9. The healing of bony defects by cell-free collagen-based scaffolds compared to stem cell-seeded tissue engineered constructs.

    LENUS (Irish Health Repository)

    Lyons, Frank G

    2010-12-01

    One of the key challenges in tissue engineering is to understand the host response to scaffolds and engineered constructs. We present a study in which two collagen-based scaffolds developed for bone repair: a collagen-glycosaminoglycan (CG) and biomimetic collagen-calcium phosphate (CCP) scaffold, are evaluated in rat cranial defects, both cell-free and when cultured with MSCs prior to implantation. The results demonstrate that both cell-free scaffolds showed excellent healing relative to the empty defect controls and somewhat surprisingly, to the tissue engineered (MSC-seeded) constructs. Immunological analysis of the healing response showed higher M1 macrophage activity in the cell-seeded scaffolds. However, when the M2 macrophage response was analysed, both groups (MSC-seeded and non-seeded scaffolds) showed significant activity of these cells which are associated with an immunomodulatory and tissue remodelling response. Interestingly, the location of this response was confined to the construct periphery, where a capsule had formed, in the MSC-seeded groups as opposed to areas of new bone formation in the non-seeded groups. This suggests that matrix deposited by MSCs during in vitro culture may adversely affect healing by acting as a barrier to macrophage-led remodelling when implanted in vivo. This study thus improves our understanding of host response in bone tissue engineering.

  10. CAROTID ATHEROSCLEROTIC LESION IN YOUNG PATIENTS

    Directory of Open Access Journals (Sweden)

    N. V. Pizova

    2014-01-01

    Full Text Available Objective: to determine the incidence of atherosclerotic lesions in the carotid and vertebral arteries of young patients from Doppler ultrasound data and to compare the quantitatively assessed traditional risk factors of coronary heart disease (CHD with severe extracranial artery atherosclerotic lesion.Subjects and methods. Doppler ultrasound was carried out evaluating structural changes in the aortic arch branches in 1563 railway transport workers less than 45 years of age. A separate sample consisted of 68 young people with carotid atherosclerotic changes, in whom traditional risk factors for CHD were studied, so were in a control group of individuals without atherosclerotic changes (n = 38.Results. Among the examinees, carotid atherosclerotic lesion was detected in 112 (7.1 % cases, the increase in the rate of atherosclerotic plaques in patients aged 35–45 years being 9.08 %; that in the rate of local intima-media thickness in those aged 31–40 years being 5.1 %. Smoking (particularly that along with hypercholesterolemia and a family history of cardiovascular diseases, obesity (along with low activity, and emotional overstrain were defined as important risk factors in the young patients. Moreover, factor analysis has shown that smoking,hypertension, and early cardiovascular pathology in the next of kin makes the greatest contribution to the development of carotid atherosclerotic lesion.Conclusion. Among the patients less than 45 years of age, carotid and vertebral artery atherosclerotic changes were found in 112 (7.1 % cases, which were more pronounced in male patients. Smoking, particularly along with hypercholesterolemia and genetic predisposition to cardiovascular diseases, was a risk factor that had the highest impact on the degree of atherosclerotic lesion in the aortic arch branches of the young patients.

  11. Amniotic mesenchymal stem cells enhance wound healing in diabetic NOD/SCID mice through high angiogenic and engraftment capabilities.

    Directory of Open Access Journals (Sweden)

    Sung-Whan Kim

    Full Text Available Although human amniotic mesenchymal stem cells (AMMs have been recognised as a promising stem cell resource, their therapeutic potential for wound healing has not been widely investigated. In this study, we evaluated the therapeutic potential of AMMs using a diabetic mouse wound model. Quantitative real-time PCR and ELISA results revealed that the angiogenic factors, IGF-1, EGF and IL-8 were markedly upregulated in AMMs when compared with adipose-derived mesenchymal stem cells (ADMs and dermal fibroblasts. In vitro scratch wound assays also showed that AMM-derived conditioned media (CM significantly accelerated wound closure. Diabetic mice were generated using streptozotocin and wounds were created by skin excision, followed by AMM transplantation. AMM transplantation significantly promoted wound healing and increased re-epithelialization and cellularity. Notably, transplanted AMMs exhibited high engraftment rates and expressed keratinocyte-specific proteins and cytokeratin in the wound area, indicating a direct contribution to cutaneous closure. Taken together, these data suggest that AMMs possess considerable therapeutic potential for chronic wounds through the secretion of angiogenic factors and enhanced engraftment/differentiation capabilities.

  12. IL-6/STAT3/TFF3 signaling regulates human biliary epithelial cell migration and wound healing in vitro.

    Science.gov (United States)

    Jiang, Gui-xing; Zhong, Xiang-yu; Cui, Yun-fu; Liu, Wei; Tai, Sheng; Wang, Zhi-dong; Shi, Yu-guang; Zhao, Shi-yong; Li, Chun-long

    2010-12-01

    Interleukin-6 (IL-6), through activation of the signal transducer and activator of transcription 3 (STAT3) and trefoil factor family 3 (TFF3), has been implicated in the promotion of mouse biliary epithelial cell (BEC) proliferation and migration. However, it is still unclear whether the IL-6/STAT3/TFF3 signaling had similar effects on human BECs. Here, we showed that exposure of human BECs to recombinant IL-6 resulted in STAT3 phosphorylation and increased the expression of TFF3 at both mRNA and protein levels. Moreover, inhibition of STAT3 using RNA interference significantly abrogated IL-6-induced TFF3 expression. In an in-vitro wound healing model, IL-6 facilitated human BEC migration. This promotion of cell migration by IL-6 was blocked when STAT3 was knocked down. Interestingly, the addition of exogenous TFF3 could rescue the cell migration defects caused by STAT3 silencing. In conclusion, our data indicate that STAT3 plays a critical role in IL-6-induced TFF3 expression in human BECs and the IL-6/STAT3/TFF3 signaling is involved in human BEC migration and wound healing.

  13. Anti-atherosclerotic effects of konjac

    Directory of Open Access Journals (Sweden)

    Hidekatsu Yanai

    2015-04-01

    Full Text Available Definition: The Konjac plant comes from the genus Amorphophallus. Japanese food uses Konjac cake. Konjac contains almost no calories and a great amount of dietary fiber. Here, we reviewed possible anti-atherosclerotic effects of konjac, using the search Pubmed ®. Konjac ingestion is likely beneficially associated with obesity, blood pressure, lipid and glucose metabolism. However, evidence is lacking on the relationship between konjac ingestion and development of atherosclerotic diseases. To more fully understand the anti-atherosclerotic effects of konjac, future studies, preferably with larger numbers of subjects, will be performed.

  14. The Protective Effect of Apamin on LPS/Fat-Induced Atherosclerotic Mice

    Directory of Open Access Journals (Sweden)

    Soo-Jung Kim

    2012-01-01

    Full Text Available Apamin, a peptide component of bee venom (BV, has anti-inflammatory properties. However, the molecular mechanisms by which apamin prevents atherosclerosis are not fully understood. We examined the effect of apamin on atherosclerotic mice. Atherosclerotic mice received intraperitoneal (ip injections of lipopolysaccharide (LPS, 2 mg/kg to induce atherosclerotic change and were fed an atherogenic diet for 12 weeks. Apamin (0.05 mg/kg was administered by ip injection. LPS-induced THP-1-derived macrophage inflammation treated with apamin reduced expression of tumor necrosis factor (TNF-α, vascular cell adhesion molecule (VCAM-1, and intracellular cell adhesion molecule (ICAM-1, as well as the nuclear factor kappa B (NF-κB signaling pathway. Apamin decreased the formation of atherosclerotic lesions as assessed by hematoxylin and elastic staining. Treatment with apamin reduced lipids, Ca2+ levels, and TNF-α in the serum from atherosclerotic mice. Further, apamin significantly attenuated expression of VCAM-1, ICAM-1, TGF-β1, and fibronectin in the descending aorta from atherosclerotic mice. These results indicate that apamin plays an important role in monocyte/macrophage inflammatory processing and may be of potential value for preventing atherosclerosis.

  15. The Effect of Mesenchymal Stem Cells and Chitosan Gel on Full Thickness Skin Wound Healing in Albino Rats: Histological, Immunohistochemical and Fluorescent Study.

    Directory of Open Access Journals (Sweden)

    Abir O El Sadik

    Full Text Available Wound healing involves the integration of complex biological processes. Several studies examined numerous approaches to enhance wound healing and to minimize its related morbidity. Both chitosan and mesenchymal stem cells (MSCs were used in treating skin wounds. The aim of the current work was to compare MSCs versus chitosan in wound healing, evaluate the most efficient route of administration of MSCs, either intradermal or systemic injection, and elicit the mechanisms inducing epidermal and dermal cell regeneration using histological, immunohistochemical and fluorescent techniques.Forty adult male Sprague Dawley albino rats were divided into four equal groups (ten rats in each group: control group (Group I; full thickness surgical skin wound model, Group II: Wound and chitosan gel. Group III: Wound treated with systemic injection of MSCs and Group IV: Wound treated with intradermal injection of MSCs. The healing ulcer was examined on day 3, 5, 10 and 15 for gross morphological evaluation and on day 10 and 15 for histological, immunohistochemical and fluorescent studies.Chitosan was proved to promote wound healing more than the control group but none of their wound reached complete closure. Better and faster healing of wounds in MSCs treated groups were manifested more than the control or chitosan treated groups. It was found that the intradermal route of administration of stem cells enhanced the rate of healing of skin wounds better than the systemic administration to the extent that, by the end of the fifteenth day of the experiment, the wounds were completely healed in all rats of this group. Histologically, the wound areas of group IV were hardly demarcated from the adjacent normal skin and showed complete regeneration of the epidermis, dermis, hypodermis and underlying muscle fibers. Collagen fibers were arranged in many directions, with significant increase in their area percent, surrounding fully regenerated hair follicles and sebaceous

  16. Cells and Tissue Interactions with Glycated Collagen and their Relevance to Delayed Diabetic Wound Healing

    OpenAIRE

    LIAO, HUIJUAN; Zakhaleva, Julia; Chen, Weiliam

    2009-01-01

    Dermal accumulation of advanced glycation end products (AGEs) has increasingly been implicated as the underlying cause of delayed diabetic wound healing. Devising an in vitro model to adequately mimic glycated tissues will facilitate investigation into the mechanism of glycation in conjunction with exploration of new approaches or improvement of current therapies for treating diabetic chronic wounds. Collagen matrices were artificially glycated and the presence of AGEs was demonstrated by imm...

  17. Loss of CAR promotes migration and proliferation of HaCaT cells, and accelerates wound healing in rats via Src-p38 MAPK pathway

    Science.gov (United States)

    Su, Linlin; Fu, Lanqing; Li, Xiaodong; Zhang, Yue; Li, Zhenzhen; Wu, Xue; Li, Yan; Bai, Xiaozhi; Hu, Dahai

    2016-01-01

    The coxsackie and adenovirus receptor (CAR) is a cell adhesion molecule mostly localized to cell-cell contacts in epithelial and endothelial cells. CAR is known to regulate tumor progression, however, its physiological role in keratinocyte migration and proliferation, two essential steps in re-epithelialization during wound healing, has less been investigated. Here we showed that CAR was predominantly expressed in the epidermis of human skin, CAR knockdown by RNAi significantly accelerated HaCaT cell migration and proliferation. In addition, knockdown of CAR in vitro increased p-Src, p-p38, and p-JNK protein levels; however, Src inhibitor PP2 prevented the increase of p-Src and p-p38 induced by CAR RNAi, but not p-JNK, and decelerated cell migration and proliferation. More intriguingly, in vivo CAR RNAi on the skin area surrounding the wounds on rat back visually accelerated wound healing and re-epithelialization process, while treatment with PP2 or p38 inhibitor SB203580 obviously inhibited these effects. By contrast, overexpressing CAR in HaCaT cells significantly decelerated cell migration and proliferation. Above results demonstrate that suppression of CAR could accelerate HaCaT cell migration and proliferation, and promote wound healing in rat skin, probably via Src-p38 MAPK pathway. CAR thus might serve as a novel therapeutic target for facilitating wound healing. PMID:26804208

  18. WOUND HEALING IN DIABETIC ULCER

    OpenAIRE

    Ida Bagus Putra Pramana; Ketut Putu Yasa

    2013-01-01

    The mechanism of wound healing is a complex mechanism and involves a variety of cells. Injury is defined as a disruption of normal structure and function. Various types of growth factors and cytokines such as platelet derived growth factor and transforming growth factor beta involved in the mechanism of wound healing. There are four phases of wound healing mechanisms : hemostasis, inflammatory, proliferative, and remodeling. Diabetic ulcers is one major complication, occurring in 15% of patie...

  19. Local transplantation of osteogenic pre-differentiated autologous adipose-derived mesenchymal stem cells may accelerate non-union fracture healing with limited pro-metastatic potency.

    Science.gov (United States)

    Han, Duanyang; Han, Na; Zhang, Peixun; Jiang, Baoguo

    2015-01-01

    Fracture non-union is a serious complication in orthopedic clinical practice. Mesenchymal stem cells are believed to play a vital role in fracture healing process. Among various origins of mesenchymal stem cell, adipose derived stem cells hold great promise especially in clinical milieu. However, the wide spread application of mesenchymal stem cell based therapy is impeded by the pro-metastasis nature of the mesenchymal stem cell itself. Based on the findings from previous studies, we hypothesize that local transplanted osteogenic pre-differentiatiated adipose stem cell may promote the non-union fracture healing. Moreover, the pre-differnetiation stem cells by down-regulating the expression of CCL5 and CCL2. This novel osteogenic pre-differnetiation technique may help clinical orthopedists to resolve the refractory non-union cases and shed new light on other stem cell based therapies to counteract to avoid the pro-metastasis nature of the mesenchymal stem cells. PMID:25785146

  20. Evaluation of early healing events around mesenchymal stem cell-seeded collagen-glycosaminoglycan scaffold. An experimental study in Wistar rats.

    LENUS (Irish Health Repository)

    Alhag, Mohamed

    2011-03-01

    Tissue engineering using cell-seeded biodegradable scaffolds offers a new bone regenerative approach that might circumvent many of the limitations of current therapeutic modalities. The aim of this experiment was to study the early healing events around mesenchymal stem cell-seeded collagen-glycosaminoglycan scaffolds.

  1. Healing singing

    OpenAIRE

    Gretsch, Renate

    2013-01-01

    This study confirms the hypothesis that healing singing leads to positive emotional experiences in relation to other people through social resonance and a strong shared bond. People who have had negative interpersonal relationship experiences that have led to depression and fear respond favourably to healing singing, because it makes a positive encounter possible. Even if their resonance ability is limited by their illness, they can be reached through music, which allows them to slowly start ...

  2. Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts

    DEFF Research Database (Denmark)

    Schneider, Linda; Cammer, Michael; Lehman, Jonathan;

    2010-01-01

    during embryonic development and a chemoattractant during postnatal migratory responses including wound healing. We previously showed that PDGFRalpha signaling is coordinated by the primary cilium in quiescent cells. However, little is known about the function of the primary cilium in cell migration....... Here we used micropipette analysis to show that a normal chemosensory response to PDGF-AA in fibroblasts requires the primary cilium. In vitro and in vivo wound healing assays revealed that in ORPK mouse (IFT88(Tg737Rpw)) fibroblasts, where ciliary assembly is defective, chemotaxis towards PDGF......-AA is absent, leading to unregulated high speed and uncontrolled directional cell displacement during wound closure, with subsequent defects in wound healing. These data suggest that in coordination with cytoskeletal reorganization, the fibroblast primary cilium functions via ciliary PDGFRalpha signaling...

  3. Nerve growth factor injected into the gastric ulcer base incorporates into endothelial, neuronal, glial and epithelial cells: implications for angiogenesis, mucosal regeneration and ulcer healing.

    Science.gov (United States)

    Tanigawa, T; Ahluwalia, A; Watanabe, T; Arakawa, T; Tarnawski, A S

    2015-08-01

    A previous study has demonstrated that locally administered growth factors such as epidermal growth factor, basic fibroblast growth factor and hepatocyte growth factor can accelerate healing of experimental gastric ulcers in rats. That study indicates that locally administered growth factors can exert potent biological effects resulting in enhanced gastric ulcers healing. However, the fate of injected growth factors, their retention and localization to specific cellular compartments have not been examined. In our preliminary study, we demonstrated that local injection of nerve growth factor to the base of experimental gastric ulcers dramatically accelerates ulcer healing, increases angiogenesis - new blood vessel formation, and improves the quality of vascular and epithelial regeneration. Before embarking on larger, definitive and time sequence studies, we wished to determine whether locally injected nerve growth factor is retained in gastric ulcer's tissues and taken up by specific cells during gastric ulcer healing. Gastric ulcers were induced in anesthetized rats by local application of acetic acid using standard methods; and, 60 min later fluorescein isothiocyanate-labeled nerve growth factor was injected locally to the ulcer base. Rats were euthanized 2, 5 and 10 days later. Gastric specimens were obtained and processed for histology. Unstained paraffin sections were examined under a fluorescence microscope, and the incorporation of fluorescein isothiocyanate-labeled nerve growth factor into various gastric tissue cells was determined and quantified. In addition, we performed immunostaining for S100β protein that is expressed in neural components. Five and ten days after ulcer induction labeled nerve growth factor (injected to the gastric ulcer base) was incorporated into endothelial cells of blood vessels, neuronal, glial and epithelial cells, myofibroblasts and muscle cells. This study demonstrates for the first time that during gastric ulcer healing

  4. Human Wharton's Jelly Mesenchymal Stem Cells plasticity augments scar-free skin wound healing with hair growth.

    Directory of Open Access Journals (Sweden)

    Vikram Sabapathy

    Full Text Available Human mesenchymal stem cells (MSCs are a promising candidate for cell-based transplantation and regenerative medicine therapies. Thus in the present study Wharton's Jelly Mesenchymal Stem Cells (WJ-MSCs have been derived from extra embryonic umbilical cord matrix following removal of both arteries and vein. Also, to overcome the clinical limitations posed by fetal bovine serum (FBS supplementation because of xenogeneic origin of FBS, usual FBS cell culture supplement has been replaced with human platelet lysate (HPL. Apart from general characteristic features of bone marrow-derived MSCs, wharton jelly-derived MSCs have the ability to maintain phenotypic attributes, cell growth kinetics, cell cycle pattern, in vitro multilineage differentiation plasticity, apoptotic pattern, normal karyotype-like intrinsic mesenchymal stem cell properties in long-term in vitro cultures. Moreover, the WJ-MSCs exhibited the in vitro multilineage differentiation capacity by giving rise to differentiated cells of not only mesodermal lineage but also to the cells of ectodermal and endodermal lineage. Also, WJ-MSC did not present any aberrant cell state upon in vivo transplantation in SCID mice and in vitro soft agar assays. The immunomodulatory potential assessed by gene expression levels of immunomodulatory factors upon exposure to inflammatory cytokines in the fetal WJ-MSCs was relatively higher compared to adult bone marrow-derived MSCs. WJ-MSCs seeded on decellularized amniotic membrane scaffold transplantation on the skin injury of SCID mice model demonstrates that combination of WJ-MSCs and decellularized amniotic membrane scaffold exhibited significantly better wound-healing capabilities, having reduced scar formation with hair growth and improved biomechanical properties of regenerated skin compared to WJ-MSCs alone. Further, our experimental data indicate that indocyanin green (ICG at optimal concentration can be resourcefully used for labeling of stem cells

  5. Role of Human Corneal Stroma-Derived Mesenchymal-Like Stem Cells in Corneal Immunity and Wound Healing.

    Science.gov (United States)

    Veréb, Zoltán; Póliska, Szilárd; Albert, Réka; Olstad, Ole Kristoffer; Boratkó, Anita; Csortos, Csilla; Moe, Morten C; Facskó, Andrea; Petrovski, Goran

    2016-01-01

    Corneal tissue regeneration is of crucial importance for maintaining normal vision. We aimed to isolate and cultivate human corneal stroma-derived mesenchymal stem-like cells (CSMSCs) from the central part of cadaver corneas and study their phenotype, multipotency, role in immunity and wound healing. The isolated cells grew as monolayers in vitro, expressed mesenchymal- and stemness-related surface markers (CD73, CD90, CD105, CD140b), and were negative for hematopoietic markers as determined by flow cytometry. CSMSCs were able to differentiate in vitro into fat, bone and cartilage. Their gene expression profile was closer to bone marrow-derived MSCs (BMMSCs) than to limbal epithelial stem cells (LESC) as determined by high-throughput screening. The immunosuppressive properties of CSMSCs were confirmed by a mixed lymphocyte reaction (MLR), while they could inhibit proliferation of activated immune cells. Treatment of CSMSCs by pro-inflammatory cytokines and toll-like receptor ligands significantly increased the secreted interleukin-6 (IL-6), interleukin-8 (IL-8) and C-X-C motif chemokine 10 (CXCL-10) levels, as well as the cell surface adhesion molecules. CSMSCs were capable of closing a wound in vitro under different stimuli. These cells thus contribute to corneal tissue homeostasis and play an immunomodulatory and regenerative role with possible implications in future cell therapies for treating sight-threatening corneal diseases. PMID:27195722

  6. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    Energy Technology Data Exchange (ETDEWEB)

    Noerenberg, Dominik [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); University of Munich - Grosshadern, Department of Clinical Radiology, Munich (Germany); Ebersberger, Hans U. [Heart Center Munich-Bogenhausen, Department of Cardiology and Intensive Care Medicine, Munich (Germany); Diederichs, Gerd; Hamm, Bernd [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); Botnar, Rene M. [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Makowski, Marcus R. [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

    2016-03-15

    Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

  7. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    International Nuclear Information System (INIS)

    Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

  8. Progress in corneal wound healing.

    Science.gov (United States)

    Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

    2015-11-01

    Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β (TGF-β) system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal

  9. Progress in corneal wound healing.

    Science.gov (United States)

    Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

    2015-11-01

    Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β (TGF-β) system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal

  10. Tendon Derived Stem Cells Promote Platelet-Rich Plasma Healing in Collagenase-Induced Rat Achilles Tendinopathy

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2014-12-01

    Full Text Available Background/Aims: Tendon injuries are common, difficult to cure and usually healed with fibrosis and scar tissue. The aim of this study was to evaluate tendon derived stem cells (TDSCs and platelet rich plasma (PRP in the treatment of collagenase induced Achilles tendinopathy in rat. Methods: Four and 8 weeks (n=18 after TDSCs, PRP, PRP with TDSC or PBS (control injection into collagenase or saline (sham injected rat Achilles tendon, tendon tissue was harvested and tendon quality was evaluated by histology and biomechanical testing. TDSCs were cultured and treated by 10% PRP, and the FAK/ERK1/2 signaling pathway and tenocyte-related genes were detected by western blot analysis. Results: Compared to the control, PRP treatment resulted in better healing of injured tendons with improved histological outcomes and biomechanical functions. The addition of TDSCs to PRP treatment significantly enhanced the effects of PRP treatment alone. TDSC injection alone had little effect on tendon healing. PRP and PRP with TDSC treatments of collagenase induced tendon injuries also increased the mRNA and protein expression of tenocyte-related genes (type I collagen, SCX, Tenascin C and activated the focal adhesion kinase (FAK and extracellular-regulated kinase (ERK 1/2 signaling pathways. Treatment of TDSCs in vitro with 10% PRP significantly increased the phosphorylation levels of FAK and ERK1/2 and the protein levels of tenocyte-related genes (Col I, SCX and Tenascin C. Inhibition of the FAK and ERK1/2 signaling pathways abolished the effect of PRP. Conclusion: This study concludes that PRP combined with TDSCs is potentially effective for the treatment of tendinopathy. The PRP induced, FAK and ERK1/2 dependent activation of tenocyte related genes in TDSCs in vitro suggests that the beneficial healing effect of the PRP with TDSC combination might occur by means of an improved TDSC differentiation toward the tenocyte lineage. Thus, a PRP with TDSC combination

  11. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: An in vitro study of fibroblast and keratinocyte scratch assays

    International Nuclear Information System (INIS)

    We have used in vitro scratch assays to examine the relative contribution of dermal fibroblasts and keratinocytes in the wound repair process and to test the influence of mesenchymal stem cell (MSC) secreted factors on both skin cell types. Scratch assays were established using single cell and co-cultures of L929 fibroblasts and HaCaT keratinocytes, with wound closure monitored via time-lapse microscopy. Both in serum supplemented and serum free conditions, wound closure was faster in L929 fibroblast than HaCaT keratinocyte scratch assays, and in co-culture the L929 fibroblasts lead the way in closing the scratches. MSC-CM generated under serum free conditions significantly enhanced the wound closure rate of both skin cell types separately and in co-culture, whereas conditioned medium from L929 or HaCaT cultures had no significant effect. This enhancement of wound closure in the presence of MSC-CM was due to accelerated cell migration rather than increased cell proliferation. A number of wound healing mediators were identified in MSC-CM, including TGF-β1, the chemokines IL-6, IL-8, MCP-1 and RANTES, and collagen type I, fibronectin, SPARC and IGFBP-7. This study suggests that the trophic activity of MSC may play a role in skin wound closure by affecting both dermal fibroblast and keratinocyte migration, along with a contribution to the formation of extracellular matrix.

  12. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: An in vitro study of fibroblast and keratinocyte scratch assays

    Energy Technology Data Exchange (ETDEWEB)

    Walter, M.N.M. [Institute for Science and Technology in Medicine, Keele University RJAH Orthopaedic Hospital, Oswestry, SY10 7AG (United Kingdom); School of Life and Health Science, Aston University, Aston Triangle, Birmingham, B4 7EJ (United Kingdom); Wright, K.T.; Fuller, H.R. [Institute for Science and Technology in Medicine, Keele University RJAH Orthopaedic Hospital, Oswestry, SY10 7AG (United Kingdom); MacNeil, S. [Kroto Research Institute and Centre for Nanoscience and Technology, Sheffield University, Sheffield, S1 2UE (United Kingdom); Johnson, W.E.B., E-mail: w.e.johnson@aston.ac.uk [School of Life and Health Science, Aston University, Aston Triangle, Birmingham, B4 7EJ (United Kingdom)

    2010-04-15

    We have used in vitro scratch assays to examine the relative contribution of dermal fibroblasts and keratinocytes in the wound repair process and to test the influence of mesenchymal stem cell (MSC) secreted factors on both skin cell types. Scratch assays were established using single cell and co-cultures of L929 fibroblasts and HaCaT keratinocytes, with wound closure monitored via time-lapse microscopy. Both in serum supplemented and serum free conditions, wound closure was faster in L929 fibroblast than HaCaT keratinocyte scratch assays, and in co-culture the L929 fibroblasts lead the way in closing the scratches. MSC-CM generated under serum free conditions significantly enhanced the wound closure rate of both skin cell types separately and in co-culture, whereas conditioned medium from L929 or HaCaT cultures had no significant effect. This enhancement of wound closure in the presence of MSC-CM was due to accelerated cell migration rather than increased cell proliferation. A number of wound healing mediators were identified in MSC-CM, including TGF-{beta}1, the chemokines IL-6, IL-8, MCP-1 and RANTES, and collagen type I, fibronectin, SPARC and IGFBP-7. This study suggests that the trophic activity of MSC may play a role in skin wound closure by affecting both dermal fibroblast and keratinocyte migration, along with a contribution to the formation of extracellular matrix.

  13. The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

    Science.gov (United States)

    Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

    2013-03-01

    Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

  14. Synergistic interactions of blood-borne immune cells, fibroblasts and extracellular matrix drive repair in an in vitro peri-implant wound healing model

    Science.gov (United States)

    Burkhardt, Melanie A.; Waser, Jasmin; Milleret, Vincent; Gerber, Isabel; Emmert, Maximilian Y.; Foolen, Jasper; Hoerstrup, Simon P.; Schlottig, Falko; Vogel, Viola

    2016-02-01

    Low correlations of cell culture data with clinical outcomes pose major medical challenges with costly consequences. While the majority of biomaterials are tested using in vitro cell monocultures, the importance of synergistic interactions between different cell types on paracrine signalling has recently been highlighted. In this proof-of-concept study, we asked whether the first contact of surfaces with whole human blood could steer the tissue healing response. This hypothesis was tested using alkali-treatment of rough titanium (Ti) surfaces since they have clinically been shown to improve early implant integration and stability, yet blood-free in vitro cell cultures poorly correlated with in vivo tissue healing. We show that alkali-treatment, compared to native Ti surfaces, increased blood clot thickness, including platelet adhesion. Strikingly, blood clots with entrapped blood cells in synergistic interactions with fibroblasts, but not fibroblasts alone, upregulated the secretion of major factors associated with fast healing. This includes matrix metalloproteinases (MMPs) to break down extracellular matrix and the growth factor VEGF, known for its angiogenic potential. Consequently, in vitro test platforms, which consider whole blood-implant interactions, might be superior in predicting wound healing in response to biomaterial properties.

  15. 5. Accelerated Fracture Healing Targeting Periosteal Cells: Possibility of Combined Therapy of Low-Intensity Pulsed Ultrasound (LIPUS), Bone Graft, and Growth Factor (bFGF).

    Science.gov (United States)

    Uchida, Kentaro; Urabe, Ken; Naruse, Koji; Mikuni-Takagaki, Yuko; Inoue, Gen; Takaso, Masashi

    2016-08-01

    We have studied the mechanism of fracture healing, and the effect of LIPUS, bone graft and growth factor on accelerating fracture healing. We present here the results of our research. To examine callus formation cells in fracture healing, we made marrow GFP chimera mice and a fracture model of marrow mesenchymal stem cell GFP chimera mice. It was demonstrated that periosteal cells were essential for callus formation. We focused on periosteal cells and examined the effect of LIPUS. In an in vitro experiment using a cultured part of the femur, LIPUS promoted ossification of the periosteal tissue. Further, LIPUS accelerated VEGF expression in the experiment using the femoral fracture model of mice. From these results, it was suggested that activation of periosteal cells might play a role in the fracture healing mechanism of LIPUS. Next, we discussed the possibility of combined therapy of LIPUS, bone graft and growth factor. Therapy involving the topical administration of bFGF using a controlled release system and bone graft could promote callus formation. In addition, LIPUS was able to promote membranaceous ossification after the bone graft. It was suggested that combined therapy of LIPUS, bone graft and bFGF could be a new option for treating fractures. PMID:27441766

  16. Congenital Self-Healing Reticulohistiocytosis

    Science.gov (United States)

    Lee, Young H.; Talekar, Mala K.; Chung, Catherine G.; Bell, Moshe D.

    2014-01-01

    Congenital self-healing reticulohistiocytosis, also known as congenital self-healing Langerhans cell histiocytosis or Hashimoto-Pritzker disease, is a Langerhans cell histiocytosis. It is characterized by skin lesions in the newborn period in an otherwise healthy infant that show a Langerhans cell infiltrate in the skin on histological analysis. These findings subsequently spontaneously involute. This report describes two newborns who presented at birth with differing presentations of congenital self-healing reticulohistiocytosis. A review of the disorder, including diagnosis and evaluation, is presented. PMID:24578781

  17. Congenital Self-Healing Reticulohistiocytosis

    OpenAIRE

    Lee, Young H.; Talekar, Mala K; Chung, Catherine G.; Bell, Moshe D.; Zaenglein, Andrea L

    2014-01-01

    Congenital self-healing reticulohistiocytosis, also known as congenital self-healing Langerhans cell histiocytosis or Hashimoto-Pritzker disease, is a Langerhans cell histiocytosis. It is characterized by skin lesions in the newborn period in an otherwise healthy infant that show a Langerhans cell infiltrate in the skin on histological analysis. These findings subsequently spontaneously involute. This report describes two newborns who presented at birth with differing presentations of congeni...

  18. An Entropy-Based Automated Cell Nuclei Segmentation and Quantification: Application in Analysis of Wound Healing Process

    Directory of Open Access Journals (Sweden)

    Varun Oswal

    2013-01-01

    Full Text Available The segmentation and quantification of cell nuclei are two very significant tasks in the analysis of histological images. Accurate results of cell nuclei segmentation are often adapted to a variety of applications such as the detection of cancerous cell nuclei and the observation of overlapping cellular events occurring during wound healing process in the human body. In this paper, an automated entropy-based thresholding system for segmentation and quantification of cell nuclei from histologically stained images has been presented. The proposed translational computation system aims to integrate clinical insight and computational analysis by identifying and segmenting objects of interest within histological images. Objects of interest and background regions are automatically distinguished by dynamically determining 3 optimal threshold values for the 3 color components of an input image. The threshold values are determined by means of entropy computations that are based on probability distributions of the color intensities of pixels and the spatial similarity of pixel intensities within neighborhoods. The effectiveness of the proposed system was tested over 21 histologically stained images containing approximately 1800 cell nuclei, and the overall performance of the algorithm was found to be promising, with high accuracy and precision values.

  19. Healing Architecture

    DEFF Research Database (Denmark)

    Folmer, Mette Blicher; Mullins, Michael; Frandsen, Anne Kathrine

    2012-01-01

    The project examines how architecture and design of space in the intensive unit promotes or hinders interaction between relatives and patients. The primary starting point is the relatives. Relatives’ support and interaction with their loved ones is important in order to promote the patients healing...... process. Therefore knowledge on how space can support interaction is fundamental for the architect, in order to make the best design solutions. Several scientific studies document that the hospital's architecture and design are important for human healing processes, including how the physical environment...... architectural and design solutions in order to improve quality of interaction between relative and patient in the hospital's intensive unit....

  20. Phenolic compounds of Chromolaena odorata protect cultured skin cells from oxidative damage: implication for cutaneous wound healing.

    Science.gov (United States)

    Phan, T T; Wang, L; See, P; Grayer, R J; Chan, S Y; Lee, S T

    2001-12-01

    Extracts from the leaves of Chromolaena odorata have been shown to be beneficial for treatment of wounds. The crude ethanol extract of the plant had been demonstrated to be a powerful antioxidant to protect fibroblasts and keratinocytes in vitro. In this study, the most active compounds were fractionated and identified from the crude extract using liquid chromatography coupled with UV spectroscopy and mass spectrometry. The antioxidant effects of purified fractions on cultured fibroblasts and keratinocytes were investigated using colorimetric and lactate hydrogenase release assay. The results showed that the phenolic acids present (protocatechuic, p-hydroxybenzoic, p-coumaric, ferulic and vanillic acids) and complex mixtures of lipophilic flavonoid aglycones (flavanones, flavonols, flavones and chalcones) were major and powerful antioxidants to protect cultured skin cells against oxidative damage. In conclusion, the extract from C odorata contains a mixture of powerful antioxidant compounds that may be one of potential mechanism contributing to enhanced wound healing. PMID:11767105

  1. Salusins: Potential Use as a Biomarker for Atherosclerotic Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Kengo Sato

    2013-01-01

    Full Text Available Human salusin-α and salusin-β are related peptides produced from prosalusin. Bolus injection of salusin-β into rats induces more profound hypotension and bradycardia than salusin-α. Central administration of salusin-β increases blood pressure via release of norepinephrine and arginine-vasopressin. Circulating levels of salusin-α and salusin-β are lower in patients with essential hypertension. Salusin-β exerts more potent mitogenic effects on human vascular smooth muscle cells (VSMCs and fibroblasts than salusin-α. Salusin-β accelerates inflammatory responses in human endothelial cells and monocyte-endothelial adhesion. Human macrophage foam cell formation is stimulated by salusin-β but suppressed by salusin-α. Chronic salusin-β infusion into apolipoprotein E-deficient mice enhances atherosclerotic lesions; salusin-α infusion reduces lesions. Salusin-β is expressed in proliferative neointimal lesions of porcine coronary arteries after stenting. Salusin-α and salusin-β immunoreactivity have been detected in human coronary atherosclerotic plaques, with dominance of salusin-β in macrophage foam cells, VSMCs, and fibroblasts. Circulating salusin-β levels increase and salusin-α levels decrease in patients with coronary artery disease. These findings suggest that salusin-β and salusin-α may contribute to proatherogenesis and antiatherogenesis, respectively. Increased salusin-β and/or decreased salusin-α levels in circulating blood and vascular tissue are closely linked with atherosclerosis. Salusin-α and salusin-β could be candidate biomarkers and therapeutic targets for atherosclerotic cardiovascular diseases.

  2. The Anti-Atherosclerotic Effect of Naringin Is Associated with Reduced Expressions of Cell Adhesion Molecules and Chemokines through NF-κB Pathway

    OpenAIRE

    Tun-Pin Hsueh; Jer-Ming Sheen; Pang, Jong-Hwei S.; Kuo-Wei Bi; Chao-Chun Huang; Hsiao-Ting Wu; Sheng-Teng Huang

    2016-01-01

    Naringin has been reported to have an anti-atherosclerosis effect but the underlying mechanism is not fully understood. The aim of this study is to investigate the impact of naringin on the TNF-α-induced expressions of cell adhesion molecules, chemokines and NF-κB signaling pathway in human umbilical vein endothelial cells (HUVECs). The experiments revealed that naringin, at concentrations without cytotoxicity, dose-dependently inhibited the adhesion of THP-1 monocytes to the TNF-α-stimulated...

  3. Heparin-Based Coacervate of FGF2 Improves Dermal Regeneration by Asserting a Synergistic Role with Cell Proliferation and Endogenous Facilitated VEGF for Cutaneous Wound Healing.

    Science.gov (United States)

    Wu, Jiang; Ye, Jingjing; Zhu, Jingjing; Xiao, Zecong; He, Chaochao; Shi, Hongxue; Wang, Yadong; Lin, Cai; Zhang, Hongyu; Zhao, Yingzheng; Fu, Xiaobing; Chen, Hong; Li, Xiaokun; Li, Lin; Zheng, Jie; Xiao, Jian

    2016-06-13

    Effective wound healing requires complicated, coordinated interactions and responses at protein, cellular, and tissue levels involving growth factor expression, cell proliferation, wound closure, granulation tissue formation, and vascularization. In this study, we develop a heparin-based coacervate consisting of poly(ethylene argininylaspartate digylceride) (PEAD) as a storage matrix, heparin as a bridge, and fibroblast growth factor-2 (FGF2) as a cargo (namely heparin-FGF2@PEAD) for wound healing. First, in vitro characterization demonstrates the loading efficiency and control release of FGF2 from the heparin-FGF2@PEAD coacervate. The following in vivo studies examine the wound healing efficiency of the heparin-FGF2@PEAD coacervate upon delivering FGF2 to full-thickness excisional skin wounds in vivo, in comparison with the other three control groups with saline, heparin@PEAD as vehicle, and free FGF2. Collective in vivo data show that controlled release of FGF2 to the wounds by the coacervate significantly accelerates the wound healing by promoting cell proliferation, stimulating the secretion of vascular endothelial growth factor (VEGF) for re-epithelization, collagen deposition, and granulation tissue formation, and enhancing the expression of platelet endothelial cell adhesion molecule (CD31) and alpha-smooth muscle actin (α-SMA) for blood vessel maturation. In parallel, no obvious wound healing effect is found for the control, vehicle, and free FGF2 groups, indicating the important role of the coavervate in the wound healing process. This work designs a suitable delivery system that can protect and release FGF2 in a sustained and controlled manner, which provides a promising therapeutic potential for topical treatment of wounds.

  4. Enhanced Wound Healing, Kinase and Stem Cell Marker Expression in Diabetic Organ-Cultured Human Corneas Upon MMP-10 and Cathepsin F Gene Silencing

    OpenAIRE

    Saghizadeh, Mehrnoosh; Epifantseva, Irina; Hemmati, David M.; Ghiam, Chantelle A.; Brunken, William J; Ljubimov, Alexander V

    2013-01-01

    Adenovirus-driven shRNA silencing of select proteinases upregulated in diabetic corneas restored normal wound healing time, the expression of diabetes-altered markers including limbal stem cell markers, and patterns of activated EGFR and Akt in human diabetic corneal organ cultures. The maximum effect was obtained combining proteinase shRNA with c-met overexpression.

  5. Priming of mononuclear cells with a combination of growth factors enhances wound healing via high angiogenic and engraftment capabilities.

    Science.gov (United States)

    Jin, Enze; Kim, Jong-Min; Kim, Sung-Whan

    2013-12-01

    Recently, we demonstrated that a specific combination of growth factors enhances the survival, adhesion and angiogenic potential of mononuclear cells (MNCs). In this study, we sought to investigate the changes of the angiogenic potential of MNCs after short-time priming with a specific combination of growth factors. MNCs were isolated using density gradient centrifugation and incubated with a priming cocktail containing epidermal growth factor (EGF), insulin-like growth factor (IGF)-1, fibroblast growth factor (FGF)-2, FMS-like tyrosine kinase (Flt)-3L , Angiopoietin (Ang)-1, granulocyte chemotactic protein (GCP)-2 and thrombopoietin (TPO) (all 400 ng/ml) for 15, 30 and 60 min. Wounds in nonobese diabetic-severe combined immune deficiency (NOD-SCID) mice were created by skin excision followed by cell transplantation. We performed a qRT-PCR analysis on the growth factor-primed cells. The angiogenic factors vascular endothelial growth factor (VEGF)-A, FGF-2, hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and interleukin (IL)-8 and the anti-apoptotic factors IGF-1 and transforming growth factor-β1 were significantly elevated in the MNCs primed for 30 min. (T30) compared with the non-primed MNCs (T0). The scratch wound assay revealed that T30- conditioned media (CM) significantly increased the rate of fibroblast-mediated wound closure compared with the rates from T0-CM and human umbilical vein endothelial cells (HUVEC)-CM at 20 hrs. In vivo wound healing results revealed that the T30-treated wounds demonstrated accelerated wound healing at days 7 and 14 compared with those treated with T0. The histological analyses demonstrated that the number of engrafted cells and transdifferentiated keratinocytes in the wounds were significantly higher in the T30-transplanted group than in the T0-transplanted group. In conclusion, this study suggests that short-term priming of MNCs with growth factors might be alternative therapeutic option for cell

  6. The Role of Microscopy in Understanding Atherosclerotic Lysosomal Lipid Metabolism

    Science.gov (United States)

    Gray Jerome, W.; Yancey, Patricia G.

    2003-02-01

    Microscopy has played a critical role in first identifying and then defining the role of lysosomes in formation of atherosclerotic foam cells. We review the evidence implicating lysosomal lipid accumulation as a factor in the pathogenesis of atherosclerosis with reference to the role of microscopy. In addition, we explore mechanisms by which lysosomal lipid engorgement occurs. Low density lipoproteins which have become modified are the major source of lipid for foam cell formation. These altered lipoproteins are taken into the cell via receptor-mediated endocytosis and delivered to lysosomes. Under normal conditions, lipids from these lipoproteins are metabolized and do not accumulate in lysosomes. In the atherosclerotic foam cell, this normal metabolism is inhibited so that cholesterol and cholesteryl esters accumulate in lysosomes. Studies of cultured cells incubated with modified lipoproteins suggests this abnormal metabolism occurs in two steps. Initially, hydrolysis of lipoprotein cholesteryl esters occurs normally, but the resultant free cholesterol cannot exit the lysosome. Further lysosomal cholesterol accumulation inhibits hydrolysis, producing a mixture of cholesterol and cholesteryl esters within swollen lysosomes. Various lipoprotein modifications can produce this lysosomal engorgement in vitro and it remains to be seen which modifications are most important in vivo.

  7. CXCL13 Promotes the Effect of Bone Marrow Mesenchymal Stem Cells (MSCs on Tendon-Bone Healing in Rats and in C3HIOT1/2 Cells

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    Feng Tian

    2015-01-01

    Full Text Available Objectives: Mesenchymal stem cells (MSCs are potential effective therapy for tissue repair and bone regeneration. In present study, the effects of CXC chemokine ligand-13 (CXCL13 were evaluated on tendon-bone healing of rats. Methods: Tendon bone healing of the rat model was established and biomechanical testing was performed at 2, 4, 8 weeks after surgery. Murine mesenchymal cell line (C3HIOT1/2 cells was cultured. The expression of miRNA-23a was detected by real-time PCR. The protein expression of ERK1/2, JNK and p38 was detected by western blotting. MiR-23a mimic and inhibitor were used to overexpress or silence the expression of miR-23a. Results: MSCs significantly elevated the levels of ultimate load to failure, stiffness and stress in specimens of rats, the effects of which were enhanced by CXCL13. The expression of miR-23a was down-regulated and the protein of ERK1/2 level was up-regulated by CXCL13 treatment in both in vivo and in vitro experiments. ERK1/2 expression was elevated by overexpression of miR-23a and reduced by miR-23a inhibitor. Conclusions: These findings revealed that CXCL13 promoted the tendon-bone healing in rats with MSCs treatment, and implied that the activation of ERK1/2 via miR-23a was involved in the process of MSCs treated bone regeneration.

  8. Cardiovascular magnetic resonance in carotid atherosclerotic disease

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    Chen Huijun

    2009-12-01

    Full Text Available Abstract Atherosclerosis is a chronic, progressive, inflammatory disease affecting many vascular beds. Disease progression leads to acute cardiovascular events such as myocardial infarction, stroke and death. The diseased carotid alone is responsible for one third of the 700,000 new or recurrent strokes occurring yearly in the United States. Imaging plays an important role in the management of atherosclerosis, and cardiovascular magnetic resonance (CMR of the carotid vessel wall is one promising modality in the evaluation of patients with carotid atherosclerotic disease. Advances in carotid vessel wall CMR allow comprehensive assessment of morphology inside the wall, contributing substantial disease-specific information beyond luminal stenosis. Although carotid vessel wall CMR has not been widely used to screen for carotid atherosclerotic disease, many trials support its potential for this indication. This review summarizes the current state of knowledge regarding carotid vessel wall CMR and its potential clinical application for management of carotid atherosclerotic disease.

  9. Serum cyclin-dependent kinase 9 is a potential biomarker of atherosclerotic inflammation

    Science.gov (United States)

    Han, Yeming; Zhao, Shanshan; Gong, Yaoqin; Hou, Guihua

    2016-01-01

    Atherosclerotic coronary artery disease (CAD) is one of the most prevalent diseases worldwide. Atherosclerosis was considered to be the single most important contributor to CAD. In this study, a distinct serum protein expression pattern in CAD patients was demonstrated by proteomic analysis with two-dimensional gel electrophoresis coupled with mass spectrometry. In particular, CDK9 was found to be highly elevated in serum, monocytes and artery plaque samples of CAD patients. Furthermore, there was high infiltration of CD14+ monocytes/macrophages within artery plaques correlated with the expression of CDK9. Moreover, Flavopiridol (CDK9 inhibitor) could inhibit THP-1 cell (monocytic acute leukemia cell line) proliferation by targeting CDK9. Altogether, These findings indicate that CDK9 represent an important role for inflammation in the pathogenesis of atherosclerosis. It may be a potential biomarker of atherosclerotic inflammation and offer insights into the pathophysiology and targeted therapy for atherosclerotic CAD. PMID:26636538

  10. Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF Factor on Corneal Epithelial Cells in Corneal Wound Healing Model.

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    Chang Rae Rho

    Full Text Available Granulocyte-macrophage colony-stimulating factor (GM-CSF is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs. We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF. An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml. MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration.

  11. Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF) Factor on Corneal Epithelial Cells in Corneal Wound Healing Model.

    Science.gov (United States)

    Rho, Chang Rae; Park, Mi-young; Kang, Seungbum

    2015-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs). We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM-CSF; rhGM-CSF). An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 μg/ml). MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 μg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration. PMID:26376304

  12. [Atherosclerotic renal artery disease management update].

    Science.gov (United States)

    Meier, Pascal; Haesler, Erik; Teta, Daniel; Qanadli, Salah Dine; Burnier, Michel

    2009-02-01

    In the case of atherosclerotic renal artery disease, the best conclusive results lie principally not in the degree of the stenosis but rather in the degree the renal parenchymal disease beyond the stenosis itself. These determining factors involve the controlling of the patients blood pressure, the improvement in the renal function and the beneficial results to the cardiovascular system. Besides the indispensable medical treatment, a revascularisation by angioplasty may be indicated. This procedure with or without vascular stent often allows satisfactory angiographic results. A treatment by surgical revascularisation is only recommended in the case of extensive atherosclerotic lesions of the aorta, complex lesions of the latter or an abdominal aortic aneurism. Although the frequency of restenosis of angioplasty with stent remains extremely low, the risk of cholesterol emboli due to the diffuse atherosclerotic lesions of the abdominal aorta, must be considered at the time of each aortic catheterization. The therapeutic approach of atherosclerotic renal artery disease must be dictated by the whole cardiovascular risk factors and by the threat of target organs. The control of the blood pressure and the maintenance of the renal function must be integrated in the decisional algorithm as well as the possible risks in carrying out an eventual revascularisation procedure. Finally, the renal angioplasty should in numerous situations be integrated in the overall assumption of responsibility of the atherosclerotic vascular diseases, and should be part of the medical treatment. Several questions still do exist; at what moment an atherosclerotic renal artery stenosis should and e considered critical, and which procedure should be considered for which patient? The purpose of this review is to propose a decisional tool for individualized treatments in the light of results from randomized and controlled studies. PMID:18815087

  13. Allogeneic Transplantation of an Adipose-Derived Stem Cell Sheet Combined With Artificial Skin Accelerates Wound Healing in a Rat Wound Model of Type 2 Diabetes and Obesity.

    Science.gov (United States)

    Kato, Yuka; Iwata, Takanori; Morikawa, Shunichi; Yamato, Masayuki; Okano, Teruo; Uchigata, Yasuko

    2015-08-01

    One of the most common complications of diabetes is diabetic foot ulcer. Diabetic ulcers do not heal easily due to diabetic neuropathy and reduced blood flow, and nonhealing ulcers may progress to gangrene, which necessitates amputation of the patient's foot. This study attempted to develop a new cell-based therapy for nonhealing diabetic ulcers using a full-thickness skin defect in a rat model of type 2 diabetes and obesity. Allogeneic adipose-derived stem cells (ASCs) were harvested from the inguinal fat of normal rats, and ASC sheets were created using cell sheet technology and transplanted into full-thickness skin defects in Zucker diabetic fatty rats. The results indicate that the transplantation of ASC sheets combined with artificial skin accelerated wound healing and vascularization, with significant differences observed 2 weeks after treatment. The ASC sheets secreted large amounts of several angiogenic growth factors in vitro, and transplanted ASCs were observed in perivascular regions and incorporated into the newly constructed vessel structures in vivo. These results suggest that ASC sheets accelerate wound healing both directly and indirectly in this diabetic wound-healing model. In conclusion, allogeneic ASC sheets exhibit potential as a new therapeutic strategy for the treatment of diabetic ulcers.

  14. Magnetic force microscopy of atherosclerotic plaque

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    Alexeeva T.A.

    2014-03-01

    Full Text Available In this work by methods of scanning probe microscopy, namely by atomic force microscopy and magnetic force microscopy the fragments of atherosclerotic plaque section of different nature were investigated. The fragments of atherosclerotic vessels with elements of immature plaque were taken during the coiled artery bypass surgery by alloprosthesis. As the result of investigation we found magnetically ordered phase of endogenous origin in the fragment of solid plaque of mixed structure. This phase is presents biogenic magnetic nanoparticles and their clusters with average size characteristic of 200-400 nm.

  15. A Tobacco-Derived Thymosin β4 Concatemer Promotes Cell Proliferation and Wound Healing in Mice.

    Science.gov (United States)

    Janarthini, Rylosona; Wang, Xiaolei; Chen, Lulu; Gao, Lei; Zhao, Lingxia

    2016-01-01

    Thymosin β4 (Tβ4) is a peptide that is known to play important roles in protection, regeneration, and remodeling of injured tissues in humans, and that shows great promise in a range of clinical applications. However, current strategies to Tβ4 are insufficient to meet growing demand and have a number of limitations. In this current study we investigated whether expression of recombinant Tβ4 in plants, specifically in tobacco (Nicotiana tabacum) leaves, represents an effective approach. To address this question, a 168 bp Tβ4 gene optimized for tobacco codon usage bias was constitutively expressed in tobacco as a 4-unit repeat concatemer, fused to a polyhistidine tag. Quantitative polymerase chain reaction and Western blot analyses were used to verify 4×Tβ4 expression in 14 transgenic tobacco lines and enzyme-linked immunosorbent assay analysis indicated 4×Tβ4 protein concentrations as high as 3 μg/g of fresh weight in the leaves. We observed that direct administration of tobacco-derived Tβ4 was more effective than Tβ4 either obtained commercially or derived from expression in Escherichia coli at promoting splenocyte proliferation in vitro and wound healing in mice through an endothelial migration assay. This study provides new insights into the development of plant-derived therapeutic proteins and their application by direct administration. PMID:27493953

  16. Rapid biomimetic mineralization of collagen fibrils and combining with human umbilical cord mesenchymal stem cells for bone defects healing.

    Science.gov (United States)

    Ye, Bihua; Luo, Xueshi; Li, Zhiwen; Zhuang, Caiping; Li, Lihua; Lu, Lu; Ding, Shan; Tian, Jinhuan; Zhou, Changren

    2016-11-01

    Collagen biomineralization is regulated by complicated interactions between the collagen matrix and non-collagenous extracellular proteins. Here, the use of sodium tripolyphosphate to simulate the templating functional motif of the C-terminal fragment of non-collagenous proteins is reported, and a low molecular weight polyacrylic acid served as a sequestration agent to stabilize amorphous calcium phosphate into nanoprecursors. Self-assembled collagen fibrils served as a fixed template for achieving rapid biomimetic mineralization in vitro. Results demonstrated that, during the mineralization process, intrafibrillar and extrafibrillar hydroxyapatite mineral with collagen fibrils formed and did so via bottom-up nanoparticle assembly based on the non-classical crystallization approach in the presence of these dual biomimetic functional analogues. In vitro human umbilical cord mesenchymal stem cell (hUCMSC) culture found that the mineralized scaffolds have a better cytocompatibility in terms of cell viability, adhesion, proliferation, and differentiation into osteoblasts. A rabbit femoral condyle defect model was established to confirm the ability of the n-HA/collagen scaffolds to facilitate bone regeneration and repair. The images of gross anatomy, MRI, CT and histomorphology taken 6 and 12weeks after surgery showed that the biomimetic mineralized collagen scaffolds with hUCMSCs can promote the healing speed of bone defects in vivo, and both of the scaffolds groups performing better than the bone defect control group. As new bone tissue formed, the scaffolds degraded and were gradually absorbed. All these results demonstrated that both of the scaffolds and cells have better histocompatibility. PMID:27523994

  17. Anti-aging effects of Piper cambodianum P. Fourn. extract on normal human dermal fibroblast cells and a wound-healing model in mice

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    Lee H

    2016-07-01

    Full Text Available Hyunji Lee,1 Youngeun Hong,1 So Hee Kwon,2 Jongsun Park,1 Jisoo Park1 1Department of Pharmacology and Medical Science, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, 2Department of Pharmacy, College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, South Korea Background: Aging of skin is associated with environmental factors such as ultraviolet rays, air pollution, gravity, and genetic factors, all of which can lead to wrinkling of skin. Previous reports suggest that the wound repair is impaired by the aging process and strategies to manipulate the age-related wound healing are necessary in order to stimulate repair.Objective: Several traditional plant extracts are well-known for their properties of skin protection and care. Piper cambodianum P. Fourn. (PPF, a member of Piperacecae, is a plant found in Vietnam that might have therapeutic properties. Therefore, the effects of PPF stem and leaf extract on aging process were investigated in vitro and in vivo.Methods: PPF extract dissolved in methanol was investigated using Western blotting, real-time quantitative reverse transcription-polymerase chain reaction, flow cytometry, and cell wound-healing assays. We assessed the anti-aging effect of PPF in mouse using the wound-healing assay. The results were analyzed by Student’s unpaired t-test; *P<0.05 and **P<0.01 were considered to indicate significant and highly significant values, respectively, compared with corresponding controls.Results: PPF treatment demonstrated in vitro and in vivo anti-aging activity. Western blot analysis of PPF-treated normal human dermal fibroblast cells showed a dose-dependent increase in the expression of extracellular matrix genes such as collagen and elastin, but decreased expression of the aging gene matrix metalloproteinase-3. Quantitative polymerase chain reaction showed

  18. Cell dynamics in the pulpal healing process following cavity preparation in rat molars.

    Science.gov (United States)

    Harada, Masahiro; Kenmotsu, Shin-Ichi; Nakasone, Naohiro; Nakakura-Ohshima, Kuniko; Ohshima, Hayato

    2008-10-01

    Odontoblast-lineage cells acquire heat-shock protein (HSP)-25-immunoreactivity (IR) after they complete their cell division, suggesting that this protein acts as a switch between cell proliferation and differentiation during tooth development. However, there are few available data concerning the relationship between cell proliferation and differentiation following cavity preparation. The present study aims to clarify the expression of HSP-25 in the odontoblast-lineage cells with their proliferative activity after cavity preparation by immunocytochemistry for HSP-25 and cell proliferation assay using 5-bromo-2'-deoxyuridine (BrdU) labeling. In untreated control teeth, intense HSP-25-IR was found in odontoblasts and some subodontoblastic mesenchymal cells. Cavity preparation caused the destruction of odontoblasts and the disappearance of HSP-25-IR was conspicuous at the affected site, although some cells retained HSP-25-IR and subsequently most of them disappeared from the pulp-dentin border by postoperative day 1. Contrary, some subodontoblastic mesenchymal cells with weak HSP-25-IR began to take the place of degenerated cells, although no proliferative activity was recognizable in the dental pulp. Interestingly, proliferative cells in the dental pulp significantly increased in number on day 2 when the newly differentiating cells already arranged along the pulp-dentin border, and continued their proliferative activity in the wide range of the pulp tissue until day 5. These findings indicate that progenitor cells equipped in the subodontoblastic layer firstly migrate and differentiate into new odontoblast-like cells to compensate for the loss of the odontoblast layer, and subsequently the reorganization of dental pulp was completed by active proliferation of the mesenchymal cells occurring in a wide range of pulp tissue.

  19. Concentrated Hypoxia-Preconditioned Adipose Mesenchymal Stem Cell-Conditioned Medium Improves Wounds Healing in Full-Thickness Skin Defect Model.

    Science.gov (United States)

    Sun, Biao; Guo, Shilei; Xu, Fei; Wang, Bin; Liu, Xiujuan; Zhang, Yuanyuan; Xu, Yan

    2014-01-01

    In recent years, the bioactive factors were utilized in exercise and athletic skin injuries. In this research, the concentrated conditioned medium of hypoxia-preconditioned adipose mesenchymal stem cells, which is rich in bioactive factor, is applied in full-thickness skin defect model to evaluate the therapeutic efficacy. Adipose mesenchymal stem cells were harvested from the abdominal subcutaneous adipose tissues. The surface markers and the potential of differentiation were analyzed. The conditioned medium of hypoxia-preconditioned stem cells was collected and freeze-dried and then applied on the rat full-thickness skin defect model, and the healing time of each group was recorded. Haematoxylin and eosin staining of skin was assessed by microscope. The characteristics of adipose mesenchymal stem cells were similar to those of other mesenchymal stem cells. The concentration of protein in freeze-dried conditioned medium in 1 mL water was about 15 times higher than in the normal condition medium. In vivo, the concentrated hypoxia-preconditioned conditioned medium can reduce the wound size and accelerate the skin wound healing. The concentrated hypoxia-preconditioned adipose mesenchymal stem cell-conditioned medium has great effect on rat model of wound healing, and it would be an ideal agent for wound care in clinical application. PMID:27433483

  20. Enhanced Healing of Diabetic Wounds by Topical Administration of Adipose Tissue-Derived Stromal Cells Overexpressing Stromal-Derived Factor-1: Biodistribution and Engraftment Analysis by Bioluminescent Imaging

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    Giuliana Di Rocco

    2011-01-01

    Full Text Available Chronic ulcers represent a major health problem in diabetic patients resulting in pain and discomfort. Conventional therapy does not guarantee adequate wound repair. In diabetes, impaired healing is partly due to poor endothelial progenitor cells mobilisation and homing, with altered levels of the chemokine stromal-derived factor-1 (SDF-1 at the wound site. Adipose tissue-associated stromal cells (AT-SCs can provide an accessible source of progenitor cells secreting proangiogenic factors and differentiating into endothelial-like cells. We demonstrated that topical administration of AT-SCs genetically modified ex vivo to overexpress SDF-1, promotes wound healing into diabetic mice. In particular, by in vivo bioluminescent imaging analysis, we monitored biodistribution and survival after transplantation of luciferase-expressing cells. In conclusion, this study indicates the therapeutic potential of AT-SCs administration in wound healing, through cell differentiation, enhanced cellular recruitment at the wound site, and paracrine effects associated with local growth-factors production.

  1. Enhancement of tendon-to-bone healing after anterior cruciate ligament reconstruction using bone marrow-derived mesenchymal stem cells genetically modified with bFGF/BMP2

    Science.gov (United States)

    Chen, Biao; Li, Bin; Qi, Yong-Jian; Ni, Qu-Bo; Pan, Zheng-Qi; Wang, Hui; Chen, Liao-Bin

    2016-01-01

    Many strategies, including various growth factors and gene transfer, have been used to augment healing after anterior cruciate ligament (ACL) reconstruction. The biological environment regulated by the growth factors during the stage of tendon-bone healing was considered important in controlling the integrating process. The purpose of this study was to evaluate the effects of bone marrow-derived mesenchymal stem cells (BMSCs) genetically modified with bone morphogenetic protein 2 (BMP2) and basic fibroblast growth factor (bFGF) on healing after ACL reconstruction. BMSCs were infected with an adenoviral vector encoding BMP2 (AdBMP2) or bFGF (AdbFGF). Then, the infected BMSCs were surgically implanted into the tendon-bone interface. At 12 weeks postoperatively, the formation of abundant cartilage-like cells, smaller tibial bone tunnel and significantly higher ultimate load and stiffness levels, through histological analysis, micro-computed tomography and biomechanical testing, were observed. In addition, the AdBMP2-plus-AdbFGF group had the smallest bone tunnel and the best mechanical properties among all the groups. The addition of BMP2 or bFGF by gene transfer resulted in better cellularity, new bone formation and higher mechanical property, which contributed to the healing process after ACL reconstruction. Furthermore, the co-application of these two genes was more powerful and efficient than either single gene therapy. PMID:27173013

  2. Enhancement of tendon-to-bone healing after anterior cruciate ligament reconstruction using bone marrow-derived mesenchymal stem cells genetically modified with bFGF/BMP2.

    Science.gov (United States)

    Chen, Biao; Li, Bin; Qi, Yong-Jian; Ni, Qu-Bo; Pan, Zheng-Qi; Wang, Hui; Chen, Liao-Bin

    2016-01-01

    Many strategies, including various growth factors and gene transfer, have been used to augment healing after anterior cruciate ligament (ACL) reconstruction. The biological environment regulated by the growth factors during the stage of tendon-bone healing was considered important in controlling the integrating process. The purpose of this study was to evaluate the effects of bone marrow-derived mesenchymal stem cells (BMSCs) genetically modified with bone morphogenetic protein 2 (BMP2) and basic fibroblast growth factor (bFGF) on healing after ACL reconstruction. BMSCs were infected with an adenoviral vector encoding BMP2 (AdBMP2) or bFGF (AdbFGF). Then, the infected BMSCs were surgically implanted into the tendon-bone interface. At 12 weeks postoperatively, the formation of abundant cartilage-like cells, smaller tibial bone tunnel and significantly higher ultimate load and stiffness levels, through histological analysis, micro-computed tomography and biomechanical testing, were observed. In addition, the AdBMP2-plus-AdbFGF group had the smallest bone tunnel and the best mechanical properties among all the groups. The addition of BMP2 or bFGF by gene transfer resulted in better cellularity, new bone formation and higher mechanical property, which contributed to the healing process after ACL reconstruction. Furthermore, the co-application of these two genes was more powerful and efficient than either single gene therapy. PMID:27173013

  3. Lipidome of atherosclerotic plaques from hypercholesterolemic rabbits.

    Science.gov (United States)

    Bojic, Lazar A; McLaren, David G; Shah, Vinit; Previs, Stephen F; Johns, Douglas G; Castro-Perez, Jose M

    2014-12-15

    The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed framework of the lipids that comprise the atherosclerotic lesion of a widely used pre-clinical model of plaque progression. Male New Zealand White rabbits were administered regular chow supplemented with 0.5% cholesterol (HC) for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our lipidomic analyses of plaques isolated from rabbits fed the HC diet, using ultra-performance liquid chromatography (UPLC) and high-resolution mass spectrometry, detected most of the major lipid classes including: Cholesteryl esters, triacylglycerols, phosphatidylcholines, sphingomyelins, diacylglycerols, fatty acids, phosphatidylserines, lysophosphatidylcholines, ceramides, phosphatidylglycerols, phosphatidylinositols and phosphatidylethanolamines. Given that cholesteryl esters, triacylglycerols and phosphatidylcholines comprise greater than 75% of total plasma lipids, we directed particular attention towards the qualitative and quantitative assessment of the fatty acid composition of these lipids. We additionally found that sphingomyelins were relatively abundant lipid class within lesions, and compared the abundance of sphingomyelins to their precursor phosphatidylcholines. The studies presented here are the first approach to a comprehensive characterization of the atherosclerotic plaque lipidome.

  4. Lipidome of Atherosclerotic Plaques from Hypercholesterolemic Rabbits

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    Lazar A. Bojic

    2014-12-01

    Full Text Available The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed framework of the lipids that comprise the atherosclerotic lesion of a widely used pre-clinical model of plaque progression. Male New Zealand White rabbits were administered regular chow supplemented with 0.5% cholesterol (HC for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our lipidomic analyses of plaques isolated from rabbits fed the HC diet, using ultra-performance liquid chromatography (UPLC and high-resolution mass spectrometry, detected most of the major lipid classes including: Cholesteryl esters, triacylglycerols, phosphatidylcholines, sphingomyelins, diacylglycerols, fatty acids, phosphatidylserines, lysophosphatidylcholines, ceramides, phosphatidylglycerols, phosphatidylinositols and phosphatidylethanolamines. Given that cholesteryl esters, triacylglycerols and phosphatidylcholines comprise greater than 75% of total plasma lipids, we directed particular attention towards the qualitative and quantitative assessment of the fatty acid composition of these lipids. We additionally found that sphingomyelins were relatively abundant lipid class within lesions, and compared the abundance of sphingomyelins to their precursor phosphatidylcholines. The studies presented here are the first approach to a comprehensive characterization of the atherosclerotic plaque lipidome.

  5. Mathematical models for atherosclerotic plaque evolution

    NARCIS (Netherlands)

    Bulelzai, M.A.K.

    2013-01-01

    Atherosclerosis is a disease in which low density lipoproteins (LDL) accumulate in the arterial wall due to an inflammatory response, which is triggered by the oxidation of LDL molecules that are already present in the arterial wall. Progression of atherosclerotic plaques involves many components wh

  6. Animal model of high cholesterol atherosclerotic erectile dysfunction and mechanism of atherosclerotic erectile dysfunction

    Institute of Scientific and Technical Information of China (English)

    Guo-ShengYang; Zhao-DianChen; Hong-JuWang

    2004-01-01

    Aim: To establish the animal model of atherosclerotic erectile dysfunction (ED) induced by high cholesterol diet and explore the mechanism of atherosclerotic ED. Methods: Thirty male rabbits were divided at random into two groups: the normal diet (ND)group (n=10) and the high cholesterol (HCH) group fed with 1.5% cholesterol diet (n=20). Serum total cholesterol, plaque areas of the ascending aorta,

  7. Comparison of cytotoxicity and wound healing effect of carboxymethylcellulose and hyaluronic acid on human corneal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Jong; Soo; Lee; Seung; Uk; Lee; Cheng-Ye; Che; Ji-Eun; Lee

    2015-01-01

    AIM: To investigate the cytotoxic effect on human corneal epithelial cells(HCECs) and the ability to faciliate corneal epithelial wound healing of carboxymethylcellulose(CMC) and hyaluronic acid(HA).METHODS: HCECs were exposed to 0.5% CMC(Refresh plus, Allergan, Irvine, California, USA) and 0.1% and 0.3%HA(Kynex , Alcon, Seoul, Korea, and Hyalein mini,Santen, Osaka, Japan) for the period of 30 min, and 4, 12,and 24 h. Methyl thiazolyl tetrazoiun(MTT)-based calorimetric assay was performed to assess the metabolic activity of cellular proliferation and lactate dehydrogenase(LDH) leakage assay to assess the cytotoxicity. apoptotic response was evaluated with flow cytometric analysis and fluorescence staining with Annexin V and propiodium iodide. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy. The wound widths were measured 24 h after confluent HCECs were scratch wounded.RESULTS: The inhibitory effect of human corneal epithelial proliferation and cytotoxicity showed the time-dependent response but no significant effect. Apoptosis developed in flow cytometry and apoptotic cells weredemonstrated in fluorescent micrograph. The damaged HCECs were detached from the bottom of the dish and showed the well-developed vacuole formations. Both CMC and HA stimulated reepithehlialization of HCECs scratched, which were more observed in CMC.CONCLUSION: CMC and HA, used in artificial tear formulation, could be utilized without any significant toxic effect on HCECs. Both significantly stimulated HCEC reepithelialization of corneal wounds.

  8. Effects of mesenchymal stem cells transfected with human hepatocyte growth factor gene on healing of burn wounds

    Institute of Scientific and Technical Information of China (English)

    HA Xiao-qin; L(U) Tong-de; HUI Ling; Dong Fang

    2010-01-01

    Objective: To explore the effects of bone marrow-derived mesenchymal stem cells (BMSCs)transfected with adenoviral vector carrying hepatocyte growth factor (HGF, Ad-HGF) on burn wound healing.Methods: BMSCs from male Wistar rats were separated and purified with Percoll separating medium by density gradient centrifugation and cultured with DMEM containing 20% fetal bovine serum (FBS). Then BMSCs were transfected with Ad-HGF at the optimal gene transduction efficiency of 100 multiplicity of infection (MOI). The efficiency of transfection and the expression of HGF in the suspension were detected by flow cytometry and enzyme linked immunosorbent assay (ELISA) respectively. Thirtytwo female rats were subjected to 90℃ water for 12 seconds to induce a partial thickness skin burn. The animals were randomly divided into mesenchymal stem cells (MSCs) treatment group (Group A), Ad-HGF treatment group (Group B),Ad-HGF-modified MSCs treatment group (Group C) and saline control group (Group D). On days 3, 5, 7, 14 and 21 postburn, HE and Sirius red stain were performed to observe the burn wound healing and collagen content. The content of hydroxyproline in wounds was also detected.Transplanted cells and the expression of(sex-determining region Y) SRY gene were detected by in situ hybridization and polymerase chain reaction (PCR), while the expression of HGF in wound tissues was detected by ELISA.Results: The result of flow cytometry showed that the transfection efficiency was 86.41% at 100 MOI. Compared with the control group, the content of HGF in the supernatant after transfection increased time-dependently and peaked at 48 h, showing significant differences at 24 h, 48 h,72 h and 96 h (P<0.01 ). Results of HE stain revealed that the range of re-epidermidalization in Group C was significantly larger than that in other groups in the first week. Three weeks postburn, the epidermis was significantly thicker in Group C than in other groups and the nails of dermis inserted into

  9. Multipotent adult progenitor cells : their role in wound healing and the treatment of dermal wounds

    NARCIS (Netherlands)

    Herdrich, B. J.; Lind, R. C.; Liechty, K. W.

    2008-01-01

    The use of cellular therapy in the treatment of dermal wounds is currently an active area of investigation. Multipotent adult progenitor cells (MAPC) are an attractive choice for cytotherapy because they have a large proliferative potential, the ability to differentiate into different cell types and

  10. Adipose Derived Mesenchymal Stem Cells In Wound Healing: A Clinical Review

    Directory of Open Access Journals (Sweden)

    Gunalp Uzun

    2014-08-01

    Full Text Available The aim of this article is to review clinical studies on the use of adipose derived mesenchymal stem cells in the treatment of chronic wounds. A search on PubMed was performed on April 30th, 2014 to identify the relevant clinical studies. We reviewed 13 articles that reported the use adipose derived stem cells in the treatment of different types of wounds. Adipose derived stem cells have the potential to be used in the treatment of chronic wounds. However, standard methods for isolation, storage and application of these cells are needed. New materials to transfer these stem cells to injured tissues should be investigated. [Dis Mol Med 2014; 2(4.000: 57-64

  11. Ultrasound Tissue Characterization of Vulnerable Atherosclerotic Plaque

    Directory of Open Access Journals (Sweden)

    Eugenio Picano

    2015-05-01

    Full Text Available A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization from a plaque in carotid arteries may result in transient ischemic attack or stroke. The atherosclerotic plaque prone to such clinical events is termed high-risk or vulnerable plaque, and its identification in humans before it becomes symptomatic has been elusive to date. Ultrasonic tissue characterization of the atherosclerotic plaque is possible with different techniques—such as vascular, transesophageal, and intravascular ultrasound—on a variety of arterial segments, including carotid, aorta, and coronary districts. The image analysis can be based on visual, video-densitometric or radiofrequency methods and identifies three distinct textural patterns: hypo-echoic (corresponding to lipid- and hemorrhage-rich plaque, iso- or moderately hyper-echoic (fibrotic or fibro-fatty plaque, and markedly hyperechoic with shadowing (calcific plaque. Hypoechoic or dishomogeneous plaques, with spotty microcalcification and large plaque burden, with plaque neovascularization and surface irregularities by contrast-enhanced ultrasound, are more prone to clinical complications than hyperechoic, extensively calcified, homogeneous plaques with limited plaque burden, smooth luminal plaque surface and absence of neovascularization. Plaque ultrasound morphology is important, along with plaque geometry, in determining the atherosclerotic prognostic burden in the individual patient. New quantitative methods beyond backscatter (to include speed of sound, attenuation, strain, temperature, and high order statistics are under development to evaluate vascular tissues. Although not yet ready for widespread clinical use, tissue characterization is listed by the American Society of Echocardiography roadmap to 2020 as one of the most promising fields of application in cardiovascular ultrasound imaging

  12. Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Constantopoulos Andreas G

    2005-10-01

    Full Text Available Abstract Background Human rhinoviruses (RV, the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. Methods Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA by flow cytometry. Results RV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation. Conclusion RV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling.

  13. Advances in the research of the role of mesenchymal stem cell in wound healing%间充质干细胞在创面愈合中的作用研究进展

    Institute of Scientific and Technical Information of China (English)

    刘玲英; 柴家科; 郁永辉; 侯玉森

    2014-01-01

    Wound healing is a dynamic and complicated process,which generally takes three overlapping phases:inflammation,proliferation,and remodeling.If wounds complicated by severe trauma,diabetes,vascular dysfunction disease,or a massive burn injury failed to pass through the three normal phases of healing,they might end up as chronic and refractory wounds.Mesenchymal stem cells (MSCs) play different important roles in the regulation of all the phases of wound healing.MSCs can be recruited into wound and differentiated into wound repair cells,as well as promote wound healing by exerting functions like anti-inflammation,anti-apoptosis,and neovascularization.This review focuses on the role and mechanism of MSCs in each phase of the wound healing process.

  14. Regional implantation of autologous adipose tissue-derived cells induces a prompt healing of long-lasting indolent digital ulcers in patients with systemic sclerosis.

    Science.gov (United States)

    Del Papa, Nicoletta; Di Luca, Gabriele; Sambataro, Domenico; Zaccara, Eleonora; Maglione, Wanda; Gabrielli, Armando; Fraticelli, Paolo; Moroncini, Gianluca; Beretta, Lorenzo; Santaniello, Alessandro; Sambataro, Gianluca; Ferraresi, Roberto; Vitali, Claudio

    2015-01-01

    Digital ulcers (DUs) are a rather frequent and invalidating complication in systemic sclerosis (SSc), often showing a very slow or null tendency to heal, in spite of the commonly used systemic and local therapeutic procedures. Recently, stem cell therapy has emerged as a new approach to accelerate wound healing. In the present study, we have tentatively treated long-lasting and poorly responsive to traditional therapy SSc-related DUs by implantation of autologous adipose tissue-derived cell (ATDC) fractions. Fifteen patients with SSc having a long-lasting DU in only one fingertip who were unresponsive to intensive systemic and local treatment were enrolled in the study. The grafting procedure consisted of the injection, at the basis of the corresponding finger, of 0.5-1 ml of autologous ATDC fractions, separated by centrifugation of adipose tissue collected through liposuction from subcutaneous abdominal fat. Time to heal after the procedure was the primary end point of the study, while reduction of pain intensity and of analgesic consumption represented a secondary end point. Furthermore, the posttherapy variation of the number of capillaries, observed in the nailfold video capillaroscopy (NVC) exam and of the resistivity in the digit arteries, measured by high-resolution echocolor-Doppler, were also taken into account. A rather fast healing of the DUs was reached in all of the enrolled patients (mean time to healing 4.23 weeks; range 2-7 weeks). A significant reduction of pain intensity was observed after a few weeks (p treatment reduction of digit artery resistivity was also recorded (p treatment of SSc-related DUs unresponsive to more consolidated therapies.

  15. Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles

    Science.gov (United States)

    Current approaches to the diagnosis and therapy of atherosclerosis cannot target to lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing in...

  16. The role of microRNA-146a in the pathogenesis of the diabetic wound-healing impairment: correction with mesenchymal stem cell treatment.

    Science.gov (United States)

    Xu, Junwang; Wu, Wenjie; Zhang, Liping; Dorset-Martin, Wanda; Morris, Michael W; Mitchell, Marc E; Liechty, Kenneth W

    2012-11-01

    The impairment in diabetic wound healing represents a significant clinical problem. Chronic inflammation is thought to play a central role in the pathogenesis of this impairment. We have previously shown that treatment of diabetic murine wounds with mesenchymal stem cells (MSCs) can improve healing, but the mechanisms are not completely defined. MicroRNA-146a (miR-146a) has been implicated in regulation of the immune and inflammatory responses. We hypothesized that abnormal miRNA-146a expression may contribute to the chronic inflammation. To test this hypothesis, we examined the expression of miRNA-146a and its target genes in diabetic and nondiabetic mice at baseline and after injury. MiR-146a expression was significantly downregulated in diabetic mouse wounds. Decreased miR-146a levels also closely correlated with increased gene expression of its proinflammatory target genes. Furthermore, the correction of the diabetic wound-healing impairment with MSC treatment was associated with a significant increase in the miR-146a expression level and decreased gene expression of its proinflammatory target genes. These results provide the first evidence that decreased expression of miR-146a in diabetic wounds in response to injury may, in part, be responsible for the abnormal inflammatory response seen in diabetic wounds and may contribute to wound-healing impairment. PMID:22851573

  17. Bone healing: little secrets

    OpenAIRE

    Einhorn, T. A.

    2011-01-01

    The development of new strategies to enhance the healing of fractures continues to evolve with the introduction of both locally and systemically delivered compounds. The recent refinement in the use of autologous bone marrow as a bone graft material has brought the field of stem cell biology into orthopaedic practice. New recombinant peptides such as platelet- derived growth factor and teriparatide show promise as local and systemic enhancers respectively. Finally, recent evidence that mutati...

  18. Histochemical and immunohistochemical analysis of ruptured atherosclerotic abdominal aortic aneurysm wall

    Directory of Open Access Journals (Sweden)

    Tanasković Irena

    2010-01-01

    Full Text Available Background/Aim. The main complication of the atherosclerotic abdominal aortic aneurism (AAA is her rupture that begins with lesion in intima and rupture. The purpose of this work was to determine immunocytochemical and morphofunctional characteristics of the cells in aortic wall in ruptured atherosclerotic abdominal aortic aneurysm. Method. During the course of this study, 20 samples of atherosclerotic AAA were analyzed, all of them obtained during authopsy. The samples were fixed in 4% formalin and embedded in paraffin. Sections of 5 μm thickness were stained histochemically (of Heidenhain azan stain and Periodic acid Schiff - PAS stain and immunocytochemically using a DAKO LSAB+/HRP technique to identify α-smooth muscle actin (α-SMA, vimentin, myosin heavy chains (MHC, desmin, S-100 protein, CD45 and CD68 (DAKO specification. Results. The results of our study showed that ruptured atherosclerotic AAA is characterized by a complete absence of endothelial cells, the disruption of basal membrane and internal elastic lamina, as well as a presence of the remains of hypocellular complicated atherosclerotic lesion in intima. On the plaque margins, as well as in the media, smooth muscle cells (SMCs are present, which express a α-SMA and vimentin (but without MHC or desmin expression, as well as leukocyte infiltration, and a large number of foam cells. Some of the foam cells show a CD68-immunoreactivity, while the others show vimentin- and S-100 protein-immunoreactivity. Media is thinned out with a disorganized elastic lamellas, while adventitia is characterized by inflammatory inflitrate (infection. Conclusion. Rupture of aneurysm occurs from the primary intimal disruption, which spreads into thinned out media and adventitia. Rupture is caused by unstable atherom, hypocellularity, loss of contractile characteristics of smooth muscle cells in intima and media, neovascularization of the media, as well as by the activity of the macrophages in the

  19. Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells.

    Science.gov (United States)

    Collette, Nicole M; Yee, Cristal S; Hum, Nicholas R; Murugesh, Deepa K; Christiansen, Blaine A; Xie, LiQin; Economides, Aris N; Manilay, Jennifer O; Robling, Alexander G; Loots, Gabriela G

    2016-07-01

    Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation of ectopic incisors, fused molars, abnormal hair follicles, and resistance to kidney disease. Sostdc1 is expressed in the periosteum, a source of osteoblasts, fibroblasts and mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated the role of Sostdc1 in bone metabolism and fracture repair. Mice lacking Sostdc1 (Sostdc1(-/-)) had a low bone mass phenotype associated with loss of trabecular bone in both lumbar vertebrae and in the appendicular skeleton. In contrast, Sostdc1(-/-) cortical bone measurements revealed larger bones with higher BMD, suggesting that Sostdc1 exerts differential effects on cortical and trabecular bone. Mid-diaphyseal femoral fractures induced in Sostdc1(-/-) mice showed that the periosteal population normally positive for Sostdc1 rapidly expands during periosteal thickening and these cells migrate into the fracture callus at 3days post fracture. Quantitative analysis of mesenchymal stem cell (MSC) and osteoblast populations determined that MSCs express Sostdc1, and that Sostdc1(-/-) 5day calluses harbor >2-fold more MSCs than fractured wildtype controls. Histologically a fraction of Sostdc1-positive cells also expressed nestin and α-smooth muscle actin, suggesting that Sostdc1 marks a population of osteochondral progenitor cells that actively participate in callus formation and bone repair. Elevated numbers of MSCs in D5 calluses resulted in a larger, more vascularized cartilage callus at day 7, and a more rapid turnover of cartilage with significantly more remodeled bone and a thicker cortical shell at 21days post fracture. These data support accelerated or enhanced bone formation/remodeling of the callus in Sostdc1(-/-) mice, suggesting that Sostdc1 may promote and maintain mesenchymal stem cell quiescence in the periosteum. PMID:27102547

  20. Xenogeneic Mesenchymal Stromal Cells Improve Wound Healing and Modulate the Immune Response in an Extensive Burn Model.

    Science.gov (United States)

    Caliari-Oliveira, Carolina; Yaochite, Juliana Navarro Ueda; Ramalho, Leandra Náira Zambelli; Palma, Patrícia Vianna Bonini; Carlos, Daniela; Cunha, Fernando de Queiróz; De Souza, Daurea Abadia; Frade, Marco Andrey Cipriani; Covas, Dimas Tadeu; Malmegrim, Kelen Cristina Ribeiro; Oliveira, Maria Carolina; Voltarelli, Julio César

    2016-01-01

    Major skin burns are difficult to treat. Patients often require special care and long-term hospitalization. Besides specific complications associated with the wounds themselves, there may be impairment of the immune system and of other organs. Mesenchymal stromal cells (MSCs) are a recent therapeutic alternative to treat burns, mainly aiming to accelerate the healing process. Several MSC properties favor their use as therapeutic approach, as they promote angiogenesis, stimulate regeneration, and enhance the immunoregulatory function. Moreover, since patients with extensive burns require urgent treatment and because the expansion of autologous MSCs is a time-consuming process, in this present study we chose to evaluate the therapeutic potential of xenogeneic MSCs in the treatment of severe burns in rats. MSCs were isolated from mouse bone marrow, expanded in vitro, and intradermally injected in the periphery of burn wounds. MSC-treated rats presented higher survival rates (76.19%) than control animals treated with PBS (60.86%, p injected GFP(+) MSCs progressively decreased over time, and 60 days after injection, few MSCs were still detected in the skin of treated animals. This study demonstrates the therapeutic effectiveness of intradermal application of MSCs in a rat model of deep burns, providing basis for future regenerative therapies in patients suffering from deep burn injuries. PMID:25955320

  1. Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood

    DEFF Research Database (Denmark)

    Anttonen, Tommi; Kirjavainen, Anna; Belevich, Ilya;

    2012-01-01

    of a basolateral membrane protein in the apical domain were observed. These defects and changes in aPKCλ/ι expression suggested that apical polarization is impaired. Following a lesion at adulthood, supporting cells with Cdc42 loss-induced maturational defects collapsed and failed to remodel F-actin belts...

  2. Identification of Target Genes Involved in Wound Healing Angiogenesis of Endothelial Cells with the Treatment of a Chinese 2-Herb Formula.

    Science.gov (United States)

    Tam, Jacqueline Chor Wing; Ko, Chun Hay; Koon, Chi Man; Cheng, Zhang; Lok, Wong Hing; Lau, Ching Po; Leung, Ping Chung; Fung, Kwok Pui; Chan, Wai Yee; Lau, Clara Bik San

    2015-01-01

    Angiogenesis is vitally important in diabetic wound healing. We had previously demonstrated that a Chinese 2-herb formula (NF3) significantly stimulated angiogenesis of HUVEC in wound healing. However, the molecular mechanism has not yet been elucidated. In line with this, global expression profiling of NF3-treated HUVEC was performed so as to assess the regulatory role of NF3 involved in the underlying signaling pathways in wound healing angiogenesis. The microarray results illustrated that different panels of differentially expressed genes were strictly governed in NF3-treated HUVEC in a time-regulated manner. The microarray analysis followed by qRT-PCR and western blotting verification of NF3-treated HUVEC at 6 h revealed the involvement of various genes in diverse biological process, e.g., MAP3K14 in anti-inflammation; SLC5A8 in anti-tumorogenesis; DNAJB7 in protein translation; BIRC5, EPCAM, INSL4, MMP8 and NPR3 in cell proliferation; CXCR7, EPCAM, HAND1 and MMP8 in migration; CXCR7, EPCAM and MMP8 in tubular formation; and BIRC5, CXCR7, EPCAM, HAND1, MMP8 and UBD in angiogenesis. After 16 h incubation of NF3, other sets of genes were shown with differential expression in HUVEC, e.g., IL1RAPL2 and NR1H4 in anti-inflammation; miR28 in anti-tumorogenesis; GRIN1 and LCN1 in anti-oxidation; EPB41 in intracellular signal transduction; PRL and TFAP2A in cell proliferation; miR28, PRL and SCG2 in cell migration; PRL in tubular formation; and miR28, NR1H4 and PRL in angiogenesis. This study provided concrete scientific evidence in support of the regulatory role of NF3 on endothelial cells involved in wound healing angiogenesis.

  3. Hepatocyte Growth Factor Effects on Mesenchymal Stem Cells Derived from Human Arteries: A Novel Strategy to Accelerate Vascular Ulcer Wound Healing

    Directory of Open Access Journals (Sweden)

    Sabrina Valente

    2016-01-01

    Full Text Available Vascular ulcers are a serious complication of peripheral vascular disease, especially in diabetics. Several approaches to treat the wounds are proposed but they show poor outcomes and require long healing times. Hepatocyte Growth Factor/Scatter Factor (HGF/SF is a pleiotropic cytokine exerting many biological activities through the c-Met receptor. This study was aimed at verifying whether HGF/SF influences proliferation, migration, and angiogenesis on mesenchymal stem cells isolated from human arteries (hVW-MSCs. hVW-MSCs were exposed to NIBSC HGF/SF (2.5, 5, 10, and 70 ng/mL from 6 hrs to 7 days. HGF and c-MET mRNA and protein expression, cell proliferation (Alamar Blue and Ki–67 assay, migration (scratch and transwell assays, and angiogenesis (Matrigel were investigated. hVW-MSCs displayed stemness features and expressed HGF and c-MET. HGF/SF did not increase hVW-MSC proliferation, whereas it enhanced the cell migration, the formation of capillary-like structures, and the expression of angiogenic markers (vWF, CD31, and KDR. The HGF/SF effects on hVW-MSC migration and angiogenic potential are of great interest to accelerate wound healing process. Local delivery of HGF/SF could therefore improve the healing of unresponsive vascular ulcers.

  4. Hepatocyte Growth Factor Effects on Mesenchymal Stem Cells Derived from Human Arteries: A Novel Strategy to Accelerate Vascular Ulcer Wound Healing.

    Science.gov (United States)

    Valente, Sabrina; Ciavarella, Carmen; Pasanisi, Emanuela; Ricci, Francesca; Stella, Andrea; Pasquinelli, Gianandrea

    2016-01-01

    Vascular ulcers are a serious complication of peripheral vascular disease, especially in diabetics. Several approaches to treat the wounds are proposed but they show poor outcomes and require long healing times. Hepatocyte Growth Factor/Scatter Factor (HGF/SF) is a pleiotropic cytokine exerting many biological activities through the c-Met receptor. This study was aimed at verifying whether HGF/SF influences proliferation, migration, and angiogenesis on mesenchymal stem cells isolated from human arteries (hVW-MSCs). hVW-MSCs were exposed to NIBSC HGF/SF (2.5, 5, 10, and 70 ng/mL) from 6 hrs to 7 days. HGF and c-MET mRNA and protein expression, cell proliferation (Alamar Blue and Ki-67 assay), migration (scratch and transwell assays), and angiogenesis (Matrigel) were investigated. hVW-MSCs displayed stemness features and expressed HGF and c-MET. HGF/SF did not increase hVW-MSC proliferation, whereas it enhanced the cell migration, the formation of capillary-like structures, and the expression of angiogenic markers (vWF, CD31, and KDR). The HGF/SF effects on hVW-MSC migration and angiogenic potential are of great interest to accelerate wound healing process. Local delivery of HGF/SF could therefore improve the healing of unresponsive vascular ulcers.

  5. Mesenchymal stem cell-laden anti-inflammatory hydrogel enhances diabetic wound healing

    OpenAIRE

    Shixuan Chen; Junbin Shi; Min Zhang; Yinghua Chen; Xueer Wang; Lei Zhang; Zhihui Tian; Yuan Yan; Qinglin Li; Wen Zhong; Malcolm Xing; Lu Zhang; Lin Zhang

    2015-01-01

    The purpose of this study was to permit bone marrow mesenchymal stem cells (BMSCs) to reach their full potential in the treatment of chronic wounds. A biocompatible multifunctional crosslinker based temperature sensitive hydrogel was developed to deliver BMSCs, which improve the chronic inflammation microenvironments of wounds. A detailed in vitro investigation found that the hydrogel is suitable for BMSC encapsulation and can promote BMSC secretion of TGF-β1 and bFGF. In vivo, full-thickness...

  6. Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells

    OpenAIRE

    Constantopoulos Andreas G; Skevaki Chrysanthi L; Gourgiotis Dimitrios; Psarras Stelios; Bossios Apostolos; Saxoni-Papageorgiou Photini; Papadopoulos Nikolaos G

    2005-01-01

    Abstract Background Human rhinoviruses (RV), the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. Methods Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxic...

  7. Epidermal stem cells in physiological tissue regeneration, wound healing and cancer

    OpenAIRE

    Füllgrabe, Anja

    2016-01-01

    The mammalian skin is a versatile organ that protects from external harm, regulates the body temperature, and provides the touch sensation. Its epithelium, the epidermis, forms several highly regenerative structures as the hair follicle (HF), the sebaceous gland (SG), and the interfollicular epidermis (IFE). Lineage tracing experiments in mice have demonstrated that several basal cell populations in the IFE and HF have the capacity to renew the epidermis during homeostasis, and also contribut...

  8. The Healing Effect of Bone Marrow-Derived Stem Cells in Knee Osteoarthritis: A Case Report

    Science.gov (United States)

    Mehrabani, Davood; Mojtahed Jaberi, Fereidoon; Zakerinia, Maryam; Hadianfard, Mohammad Javad; Jalli, Reza; Tanideh, Nader; Zare, Shahrokh

    2016-01-01

    Osteoarthritis (OA) is a prevalent chronic disease impacting on quality of life and has societal and economical burden increasing with age. Yet, no confirmed pharmacological, biological or surgical therapy could prevent the progressive destruction of OA joint. Mesenchymal stem cells (MSCs) with immunosuppressive activities emerged a potential therapy. We describe a magnetic resonance images (MRI) approved 47 years old nomad female suffering from a severe right knee OA. After intra-articular injection of 36×106 passage 2 of bone marrow-derived stem cells (BMSCs), the patient’s functional status of the knee, the number of stairs she could climb, the pain on visual analog scale (VAS) and walking distance improved after two months post-transplantation. MRI revealed an extension of the repaired tissue over subchondral bone. So as MSC transplantation is a simple technique, resulted into pain relief, minimized donor-site morbidity, provided a better quality of life, significantly improved cartilage quality with no need to hospitalization or surgery, cell transplantation can be considered as a reliable alternative treatment for chronic knee OA. Therefore these findings can be added to the literature on using BMSCs for treatment of OA. PMID:27579273

  9. The contemporary management of intracranial atherosclerotic disease.

    Science.gov (United States)

    Leng, Xinyi; Wong, Ka Sing; Leung, Thomas W

    2016-06-01

    Intracranial atherosclerotic disease is the most common cause of cerebral vasculopathy and an important stroke etiology worldwide, with a higher prevalence in Asian, Hispanic and African ethnicities. Symptomatic intracranial atherosclerotic disease portends a recurrent stroke risk as high as 18% at one year. The key to secondary prevention is an understanding of the underlying stroke mechanism and aggressive control of conventional cardiovascular risks. Contemporary treatment includes antiplatelet therapy, optimal glycemic and blood pressure control, statin therapy and lifestyle modifications. For patients with high-grade (70-99%) symptomatic steno-occlusion, short-term dual antiplatelet therapy with aspirin and clopidogrel followed by life-long single antiplatelet therapy may reduce the recurrent risk. Current evidence does not advocate percutaneous transluminal angioplasty and stenting as an initial treatment. External counterpulsation, encephaloduroarteriosynangiosis and remote limb ischemic preconditioning are treatments under investigation. Future studies should aim at predicting patients prone to recurrence despite of medical therapies and testing the efficacy of emerging therapies.

  10. Accelerated healing of diabetic wound using artificial dermis constructed with adipose stem cells and poly(L-glutamic acid)/chitosan scaffold

    Institute of Scientific and Technical Information of China (English)

    SHEN Ting; PAN Zhi-gang; ZHOU Xiao; HONG Chao-yang

    2013-01-01

    Background Diabetic wound is one of the most serious complications of diabetes mellitus.There are no significantly effective therapies for chronic non-healing diabetes ulcer so far.This study aimed to explore the feasibility of healing impaired wound using artificial dermis constructed with human adipose derived stem cells (ASCs) and poly(L-glutamic acid)/chitosan (PLGA/CS) scaffold in streptozotocin-induced diabetic mice.Methods ASCs were isolated from fresh human lipoaspirates and expanded ex vivo for three passages,and then cells were seeded onto PLGA/CS scaffold to form artificial dermis.Expression of VEGF and TGFβ1 by ASCs presented in artificial dermis was determined.The artificial dermis was transplanted to treat the 20 mm × 20 mm full-thickness cutaneous wound created on the back of diabetic mice.Wound treated with scaffold alone and without treatment,and wound in normal non-diabetic mice served as control.Results Cells growing within scaffold showed great proliferation potential,depositing abundant collagen matrix.Meanwhile,expression of VEGF and TGF-β1 by seeded ASCs maintained at a consistent high level.After treated with ASC based artificial dermis,diabetic wounds exhibited significantly higher healing rate compared with wounds treated with scaffold alone or without treatment.Histological examination also demonstrated an improvement in cutaneous restoration with matrix deposition and organization.Further quantitative analysis showed that there was a significant increase in dermis thickness and collagen content on artificial dermis treated wounds.Conclusion ASC/PLGA artificial dermis can effectively accelerate diabetic wound healing by promoting angiogenic growth factors and dermal collagen synthesis.

  11. Chlamydia pneumoniae Infection in Atherosclerotic Lesion Development through Oxidative Stress: A Brief Overview

    Directory of Open Access Journals (Sweden)

    Rosa Sessa

    2013-07-01

    Full Text Available Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading cause of respiratory tract infections and, in the last two decades, has been widely associated with atherosclerosis by seroepidemiological studies, and direct detection of the microorganism within atheroma. C. pneumoniae is presumed to play a role in atherosclerosis for its ability to disseminate via peripheral blood mononuclear cells, to replicate and persist within vascular cells, and for its pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C. pneumoniae infection has been shown to induce the production of reactive oxygen species in all the cells involved in atherosclerotic process such as macrophages, platelets, endothelial cells, and vascular smooth muscle cells, leading to oxidative stress. The aim of this review is to summarize the data linking C. pneumoniae-induced oxidative stress to atherosclerotic lesion development.

  12. Gradient Meshed and Toughened SOEC (Solid Oxide Electrolyzer Cell) Composite Seal with Self-Healing Capabilities

    Energy Technology Data Exchange (ETDEWEB)

    Kathy Lu; W. T. Reynolds, Jr.

    2010-06-08

    High-temperature electrolysis of water steam is a promising approach for hydrogen production. The potential is even more promising when abundant heat source from nuclear power reactors can be efficiently utilized. Hydrogen production through the above approach also allows for low electric consumption. Overall energy conversion efficiencies for high temperature electrolysis are in the 45-50% range compared to ~30% for the conventional electrolysis. Under such motivation, this research is focused on increasing the operation time and high temperature stability of solid oxide electrolyzer cells (SOEC) for splitting water into hydrogen. Specifically, our focus is to improve the SOEC seal thermal stability and performances by alleviating thermal stress and seal cracking issues.

  13. Autophagy in Atherosclerosis: A Phenomenon Found in Human Carotid Atherosclerotic Plaques

    Institute of Scientific and Technical Information of China (English)

    Huihui Liu; Yongjun Cao; Tong Tong; Jijun Shi; Yanlin Zhang; Yaping Yang; Chunfeng Liu

    2015-01-01

    Background:Autophagy has been found to be involved in animal and cell models ofatherosclerosis,but to date,it lacks general observation in human atherosclerotic plaques.Here,we investigated autophagy in smooth muscle cells (SMCs),endothelial cells (ECs),and macrophages in human atherosclerotic plaques via transmission electron microscopy (TEM),western blotting,and immunohistochemistry analysis.Methods:The histopathologic morphology of these plaques was observed via hematoxylin and eosin staining.The ultrastructural morphology of the SMCs,ECs,and macrophages in these plaques was observed via TEM.The localization ofmicrotubule-associated protein 1 light chain 3 (MAP 1-LC3),a relatively special maker ofautophagy,in plaques was observed by double fluorescent immunochemistty and western blotting.Results:All of these human atherosclerotic plaques were considered advanced and unstable in histologically observation.By double fluorescent immunochemistry,the expression of LC3-Ⅱ increased in the SMCs of the fibrous cap,the macrophages,and the microvascular ECs of the plaque shoulders.The protein level of LC3-Ⅱ by western blotting significantly increased in plaques compared with normal controls.In addition,TEM observation of plaques revealed certain features of autophagy in SMCs,ECs,and macrophages including the formation of myelin figures,vacuolization,and the accumulation of inclusions in the cytosol.These results indicate that autophagy is activated in SMCs,ECs,and macrophages in human advanced atherosclerotic plaques.Conclusions:Our study is to demonstrate the existence of autophagy in human atherosclerotic plaques by different methods,which may contribute to the development of pharmacological approaches to stabilize vulnerable and rupture-prone lesions.

  14. Healing of large periapical lesions following delivery of dental stem cells with an injectable scaffold: New method and three case reports

    Directory of Open Access Journals (Sweden)

    Vahab Shiehzadeh

    2014-01-01

    Full Text Available Regenerative endodontics is the creation and delivery of tissues to replace diseased, missing, and traumatized pulp. A call for a paradigm shift and new protocol for the clinical management of these cases has been brought to attention. These regenerative endodontic techniques will possibly involve some combination of disinfection or debridement of infected root canal systems with apical enlargement to permit revascularization and use of stem cells, scaffolds, and growth factors. Mesenchymal stem cells (MSCs have been isolated from the pulp tissue of permanent teeth (dental pulp stem cells (DPSCs and deciduous teeth (stem cells from human exfoliated deciduous teeth. Stem cells are characterized as multipotent cells for regeneration.These three case reports describe the treatment of necrotic or immature teeth with periradicular periodontitis, which was not treated with conventional apexification techniques. All cases presented here developed mature apices and bone healing after 3 to 4 months after the initial treatment without complications, and faster than traditional treatments. Our clinical observations support a shifting paradigm toward a biologic approach by providing a favorable environment for tissue regeneration. The mechanism of this continued development and formation of the root end and faster tissue healing is discussed.

  15. Genome-Wide Transcriptional Analysis of Differentially Expressed Genes in Diabetic, Healing Corneal Epithelial Cells: Hyperglycemia-Suppressed TGFβ3 Expression Contributes to the Delay of Epithelial Wound Healing in Diabetic Corneas

    OpenAIRE

    Bettahi, Ilham; Sun, Haijing; Gao, Nan; Wang, Feng; Mi, Xiaofan; Chen, Weiping; Liu, Zuguo; Yu, Fu-Shin X.

    2014-01-01

    Patients with diabetes mellitus (DM) may develop corneal complications and delayed wound healing. The aims of this study are to characterize the molecular signatures and biological pathways leading to delayed epithelial wound healing and to delineate the involvement of TGFβ3 therein. Genome-wide cDNA microarray analysis revealed 1,888 differentially expressed genes in the healing epithelia of normal (NL) versus type 1 DM rat corneas. Gene ontology and enrichment analyses indicated TGFβ signal...

  16. 14S,21R-Dihydroxydocosahexaenoic Acid Remedies Impaired Healing and Mesenchymal Stem Cell Functions in Diabetic Wounds*

    OpenAIRE

    Tian, Haibin; Lu, Yan; Shah, Shraddha P.; Hong, Song

    2010-01-01

    Treatment of diabetes-impaired wound healing remains a major unresolved medical challenge. Here, we identified suppressed formation of a novel reparative lipid mediator 14S,21R-dihydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21R-diHDHA) in cutaneous wounds of diabetic db/db mice. These results indicate that diabetes impedes the biosynthetic pathways of 14S,21R-diHDHA in skin wounds. Administration of exogenous 14S,21R-diHDHA to wounds in diabetic animals rescued healing and angiogen...

  17. Protective effect of policosanol on atherosclerotic lesions in rabbits with exogenous hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Arruzazabala M.L.

    2000-01-01

    Full Text Available Policosanol is a mixture of higher aliphatic alcohols purified from sugar cane wax, with cholesterol-lowering effects demonstrable in experimental models and in patients with type II hypercholesterolemia. The protective effects of policosanol on atherosclerotic lesions experimentally induced by lipofundin in rabbits and rats and spontaneously developed in stumptail monkeys have been described. The present study was conducted to determine whether policosanol administered orally to rabbits with exogenous hypercholesterolemia also protects against the development of atherosclerotic lesions. Male New Zealand rabbits weighing 1.5 to 2 kg were randomly divided into three experimental groups which received 25 or 200 mg/kg policosanol (N = 7 orally for 60 days with acacia gum as vehicle or acacia gum alone (control group, N = 9. All animals received a cholesterol-rich diet (0.5% during the entire period. Control animals developed marked hypercholesterolemia, macroscopic lesions and arterial intimal thickening. Intima thickness was significantly less (32.5 ± 7 and 25.4 ± 4 µm in hypercholesterolemic rabbits treated with policosanol than in controls (57.6 ± 9 µm. In most policosanol-treated animals, atherosclerotic lesions were not present, and in others, thickness of fatty streaks had less foam cell layers than in controls. We conclude that policosanol has a protective effect on the atherosclerotic lesions occurring in this experimental model.

  18. Stress and atherosclerotic cardiovascular disease.

    Science.gov (United States)

    Inoue, Nobutaka

    2014-01-01

    Recent major advances in medical science have introduced a wide variety of treatments against atherosclerosis-based cardiovascular diseases, which has led to a significant reduction in mortality associated with these diseases. However, atherosclerosis-based cardiovascular disease remains a leading cause of death. Furthermore, progress in medical science has demonstrated the pathogenesis of cardiovascular disease to be complicated, with a wide variety of underlying factors. Among these factors, stress is thought to be pivotal. Several types of stress are involved in the development of cardiovascular disease, including oxidative stress, mental stress, hemodynamic stress and social stress. Accumulating evidence indicates that traditional risk factors for atherosclerosis, including diabetes, hyperlipidemia, hypertension and smoking, induce oxidative stress in the vasculature. Oxidative stress is implicated in the pathogenesis of endothelial dysfunction, atherogenesis, hypertension and remodeling of blood vessels. Meanwhile, mental stress is a well-known major contributor to the development of cardiovascular disease. The cardiovascular system is constantly exposed to hemodynamic stress by the blood flow and/or pulsation, and hemodynamic stress exerts profound effects on the biology of vascular cells and cardiomyocytes. In addition, social stress, such as that due to a lack of social support, poverty or living alone, has a negative impact on the incidence of cardiovascular disease. Furthermore, there are interactions between mental, oxidative and hemodynamic stress. The production of reactive oxygen species is increased under high levels of mental stress in close association with oxidative stress. These stress responses and their interactions play central roles in the pathogenesis of atherosclerosis-based cardiovascular disease. Accordingly, the pathophysiological and clinical implications of stress are discussed in this article.

  19. Predicting Young’s Modulus of Glass/Ceramic Sealant for Solid Oxide Fuel Cell Considering the Combined Effects of Aging, Micro-Voids and Self-Healing

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wenning N.; Sun, Xin; Khaleel, Mohammad A.

    2008-12-01

    We study the temperature dependent Young’s modulus for the glass/ceramic seal material used in Solid Oxide Fuel Cells (SOFCs). With longer heat treatment or aging time during operation, further devitrification may reduce the residual glass content in the seal material while boosting the ceramic crystalline content. In the meantime, micro-voids induced by the cooling process from the high operating temperature to room temperature can potentially degrade the mechanical properties of the glass/ceramic sealant. Upon reheating to the SOFC operating temperature, possible self-healing phenomenon may occur in the glass/ceramic sealant which can potentially restore some of its mechanical properties. A phenomenological model is developed to model the temperature dependent Young’s modulus of glass/ceramic seal considering the combined effects of aging, micro-voids, and possible self-healing. An aging-time-dependent crystalline content model is first developed to describe the increase of the crystalline content due to the continuing devitrification under high operating temperature. A continuum damage mechanics (CDM) model is then adapted to model the effects of both cooling induced micro-voids and reheating induced self-healing. This model is applied to model the glass-ceramic G18, a candidate SOFC seal material previously developed at PNNL. Experimentally determined temperature dependent Young’s modulus is used to validate the model predictions

  20. Endovascular revascularization for aortoiliac atherosclerotic disease

    Science.gov (United States)

    Aggarwal, Vikas; Waldo, Stephen W; Armstrong, Ehrin J

    2016-01-01

    Atherosclerotic iliac artery disease is increasingly being treated with endovascular techniques. A number of new stent technologies can be utilized with high long-term patency, including self-expanding stents, balloon-expandable stents, and covered stents, but comparative data on these stent types and in more complex lesions are lacking. This article provides a review of currently available iliac stent technologies, as well as complex procedural aspects of iliac artery interventions, including approaches to the treatment of iliac bifurcation disease, long segment occlusions, choice of stent type, and treatment of iliac artery in-stent restenosis. PMID:27099509

  1. Mechanical model of vulnerable atherosclerotic plaque rupture

    Institute of Scientific and Technical Information of China (English)

    SU; Haijun; ZHANG; Mei; ZHANG; Yun

    2004-01-01

    Rupture of atherosclerotic plaque is the main trigger of acute cardiovascular events, but the mechanism of plaque rupture is still unknown. We have constructed a model describing the motion of the fibrous cap of the plaque using the theory of elastic mechanics and studied the stability of the plaque theoretically. It has shown that plaque rupture is the result of a dynamic interplay between factors intrinsic to the plaque itself and extrinsic factors. We have proposed a new mechanism of plaque rupture, given a new explanation about the nonlinear dynamic progress of atherosclerosis and suggested a method to identify the vulnerable plaques to manage atherosclerosis.

  2. Mesenchymal stem cells favour healing of the cutaneous radiation syndrome; Les cellules souches mesenchymateuses favorisent la cicatrisation des lesions cutanees radio induites

    Energy Technology Data Exchange (ETDEWEB)

    Francois, S.; Mouiseddine, M.; Mathieu, N.; Semont, A.; Monti, P.; Dudoignon, N.; Sache, A.; Boutarfa, A.; Thierry, D.; Voisin, P.; Gourmelon, P.; Chapel, A. [IRSN, Dir. de radioprotection de l' Homme, 92 - Fontenay-aux-Roses (France)

    2006-10-15

    It has been suggested that human Mesenchymal Stem Cells (hMSC) could be used to repair numerous injured tissues. We have studied the potential use of hMSC in order to limit radiation-induced skin lesions. Immuno-deficient NOD/SCID mice were locally irradiated to the leg (30 Gy, dose rate 2.7 Gy/mn) using a {sup 60} Co source in order to induce a severe skin lesion. Cultured bone marrow hMSC were delivered intravenously to the mice. The irradiated skin samples were studied for the presence of the human cells, the severity of the lesions and the healing process. Macroscopic analysis and histology results showed that the lesions were evolving to a less severe degree of radiation dermatitis following hMSC transplant when compared to irradiated non-transplanted controls. Clinical scores for the studied skin parameters of treated mice were significantly improved. A faster healing was observed when compared to untreated mouse. Immuno-histology and Polymerase Chain reaction (PCR) analysis provided evidence that the human cells were found in the irradiated area. These results suggest a possible use of hMSC for the treatment of the early phase of the cutaneous radiation syndrome. A successful transplant of stem cells and subsequent reduction in radiation-induced complication may open the road to completely new strategies in cutaneous radiation syndrome therapy. (authors)

  3. Self-healing circuit design inspired by prokaryotic cell%原核细胞仿生自修复电路设计

    Institute of Scientific and Technical Information of China (English)

    李岳; 王南天; 钱彦岭

    2012-01-01

    仿生电子阵列是模拟生物体自修复机制,具有在线自修复能力的新型电路.针对基于真核细胞的仿生电子阵列配置存储消耗大等不足,在比较真核细胞、原核细胞基因结构的基础上,提出了一种基于原核细胞的仿生电子阵列结构,设计实现了差分二进制相移键控调制电路,通过仿真验证了该结构的有效性.%Bio-inspired array is a new type of circuit based on the self-healing mechanism of organism. The current study presents a novel prokaryotic cell-based bio-inspired army structure based on the gene structure of eukaryotic cell and prokaryotic cell. Simulation experiment on designing a self-healing DBPSK circuit is carried out and the result shows that the presented prokaryotic cell-based bio-inspired array structure is effective and consumes less memory storage than the traditional eukaryotic array structure.

  4. The NF-κB pathway: regulation of the instability of atherosclerotic plaques activated by Fg, Fb, and FDPs.

    Science.gov (United States)

    Cao, Yongjun; Zhou, Xiaomei; Liu, Huihui; Zhang, Yanlin; Yu, Xiaoyan; Liu, Chunfeng

    2013-11-01

    Recently, the molecular mechanism responsible for the instability of atherosclerotic plaques has gradually become a hot topic among researchers and clinicians. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play an important role in the processes of formation and development of atherosclerosis. In this study, we established and employed the transwell co-culture system of rabbit aortic endothelial cells and smooth muscle cells to explore the relationship between fibrin (Fb), fibrinogen (Fg), and/or their degradation products (FDPs) in relation to the instability of atherosclerotic plaques; meanwhile, we observed the effects of Fg, Fb, and FDPs on the mRNA levels of MMPs and VEGF as well as on the activation of nuclear factor-kappa B (NF-κB). We concluded that Fb, Fg, and FDPs are involved in the progression of the instability of atherosclerotic plaques via increasing the expression of MMPs and VEGF. This effect might be mediated by the NF-кB pathway.

  5. Pregnancy loss and later risk of atherosclerotic disease

    DEFF Research Database (Denmark)

    Ranthe, Mattis Flyvholm; Andersen, Elisabeth Anne Wreford; Wohlfahrt, Jan;

    2013-01-01

    Pregnancy losses and atherosclerotic disease may be etiologically linked through underlying pathology. We examined whether miscarriage and stillbirth increase later risk of myocardial infarction, cerebral infarction, and renovascular hypertension.......Pregnancy losses and atherosclerotic disease may be etiologically linked through underlying pathology. We examined whether miscarriage and stillbirth increase later risk of myocardial infarction, cerebral infarction, and renovascular hypertension....

  6. Fast and safe fabrication of a free-standing chitosan/alginate nanomembrane to promote stem cell delivery and wound healing

    Directory of Open Access Journals (Sweden)

    Kong Y

    2016-06-01

    nanomembrane may be particularly useful for stem cell delivery and wound healing. Keywords: nanomembrane, layer-by-layer, cell delivery, wound healing

  7. Endovascular treatment of symptomatic intracranial atherosclerotic disease

    Directory of Open Access Journals (Sweden)

    Syed I Hussain

    2011-02-01

    Full Text Available Abstract: Symptomatic intracranial atherosclerotic disease (ICAD is responsible for approximately 10% of all ischemic strokes in the United States. The risk of recurrent stroke may be as high as 35% in patient with critical stenosis greater than 70% in diameter narrowing. Recent advances in medical and endovascular therapy have placed ICAD at the forefront of clinical stroke research to optimize the best medical and endovascular approach to treat this important underlying stroke etiology. Analysis of symptomatic ICAD studies lead to the question that whether angioplasty and or stenting is a safe, suitable and efficacious therapeutic strategy in patients with critical stenoses that are deemed refractory to medical management. Most of the currently available data in support of angioplasty and or stenting in high risk patients with severe symptomatic ICAD is in the form of case series and randomized trial results of endovascular therapy versus medical treatment are awaited. This is a comprehensive review of the state of the art in the endovascular approach with angioplasty and or stenting of symptomatic intracranial atherosclerotic disease.

  8. The contemporary management of intracranial atherosclerotic disease.

    Science.gov (United States)

    Leng, Xinyi; Wong, Ka Sing; Leung, Thomas W

    2016-06-01

    Intracranial atherosclerotic disease is the most common cause of cerebral vasculopathy and an important stroke etiology worldwide, with a higher prevalence in Asian, Hispanic and African ethnicities. Symptomatic intracranial atherosclerotic disease portends a recurrent stroke risk as high as 18% at one year. The key to secondary prevention is an understanding of the underlying stroke mechanism and aggressive control of conventional cardiovascular risks. Contemporary treatment includes antiplatelet therapy, optimal glycemic and blood pressure control, statin therapy and lifestyle modifications. For patients with high-grade (70-99%) symptomatic steno-occlusion, short-term dual antiplatelet therapy with aspirin and clopidogrel followed by life-long single antiplatelet therapy may reduce the recurrent risk. Current evidence does not advocate percutaneous transluminal angioplasty and stenting as an initial treatment. External counterpulsation, encephaloduroarteriosynangiosis and remote limb ischemic preconditioning are treatments under investigation. Future studies should aim at predicting patients prone to recurrence despite of medical therapies and testing the efficacy of emerging therapies. PMID:27082149

  9. Diabetes induces stable intrinsic changes to myeloid cells that contribute to chronic inflammation during wound healing in mice

    OpenAIRE

    Pauline Bannon; Sally Wood; Terry Restivo; Laura Campbell; Hardman, Matthew J.; Mace, Kimberly A

    2013-01-01

    SUMMARY Acute inflammation in response to injury is a tightly regulated process by which subsets of leukocytes are recruited to the injured tissue and undergo behavioural changes that are essential for effective tissue repair and regeneration. The diabetic wound environment is characterised by excessive and prolonged inflammation that is linked to poor progression of healing and, in humans, the development of diabetic foot ulcers. However, the underlying mechanisms contributing to excessive i...

  10. Overexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice.

    Directory of Open Access Journals (Sweden)

    Kurt Reifenberg

    Full Text Available Although macrophages represent the hallmark of both human and murine atherosclerotic lesions and have been shown to express TGF-ß1 (transforming growth factor β1 and its receptors, it has so far not been experimentally addressed whether the pleiotropic cytokine TGF-ß1 may influence atherogenesis by a macrophage specific mechanism. We developed transgenic mice with macrophage specific TGF-ß1 overexpression, crossed the transgenics to the atherosclerotic ApoE (apolipoprotein E knock-out strain and quantitatively analyzed both atherosclerotic lesion development and composition of the resulting double mutants. Compared with control ApoE(-/- mice, animals with macrophage specific TGF-ß1 overexpression developed significantly less atherosclerosis after 24 weeks on the WTD (Western type diet as indicated by aortic plaque area en face (p<0.05. Reduced atherosclerotic lesion development was associated with significantly less macrophages (p<0.05 after both 8 and 24 weeks on the WTD, significantly more smooth muscle cells (SMCs; p<0.01 after 24 weeks on the WTD, significantly more collagen (p<0.01 and p<0.05 after 16 and 24 weeks on the WTD, respectively without significant differences of inner aortic arch intima thickness or the number of total macrophages in the mice pointing to a plaque stabilizing effect of macrophage-specific TGF-ß1 overexpression. Our data shows that macrophage specific TGF-ß1 overexpression reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice.

  11. Foxo1 Inhibits Diabetic Mucosal Wound Healing but Enhances Healing of Normoglycemic Wounds

    OpenAIRE

    Xu, Fanxing; Othman, Badr; Lim, Jason; Batres, Angelika; Ponugoti, Bhaskar; Zhang, Chenying; Yi, Leah; Liu, Jian; Tian, Chen; Hameedaldeen, Alhassan; Alsadun, Sarah; Tarapore, Rohinton; Graves, Dana T.

    2014-01-01

    Re-epithelialization is an important part in mucosal wound healing. Surprisingly little is known about the impact of diabetes on the molecular events of mucosal healing. We examined the role of the transcription factor forkhead box O1 (Foxo1) in oral wounds of diabetic and normoglycemic mice with keratinocyte-specific Foxo1 deletion. Diabetic mucosal wounds had significantly delayed healing with reduced cell migration and proliferation. Foxo1 deletion rescued the negative impact of diabetes o...

  12. Hindlimb unloading alters ligament healing

    Science.gov (United States)

    Provenzano, Paolo P.; Martinez, Daniel A.; Grindeland, Richard E.; Dwyer, Kelley W.; Turner, Joanne; Vailas, Arthur C.; Vanderby, Ray Jr

    2003-01-01

    We investigated the hypothesis that hindlimb unloading inhibits healing in fibrous connective tissue such as ligament. Male rats were assigned to 3- and 7-wk treatment groups with three subgroups each: sham control, ambulatory healing, and hindlimb-suspended healing. Ambulatory and suspended animals underwent surgical rupture of their medial collateral ligaments, whereas sham surgeries were performed on control animals. After 3 or 7 wk, mechanical and/or morphological properties were measured in ligament, muscle, and bone. During mechanical testing, most suspended ligaments failed in the scar region, indicating the greatest impairment was to ligament and not to bone-ligament insertion. Ligament testing revealed significant reductions in maximum force, ultimate stress, elastic modulus, and low-load properties in suspended animals. In addition, femoral mineral density, femoral strength, gastrocnemius mass, and tibialis anterior mass were significantly reduced. Microscopy revealed abnormal scar formation and cell distribution in suspended ligaments with extracellular matrix discontinuities and voids between misaligned, but well-formed, collagen fiber bundles. Hence, stress levels from ambulation appear unnecessary for formation of fiber bundles yet required for collagen to form structurally competent continuous fibers. Results support our hypothesis that hindlimb unloading impairs healing of fibrous connective tissue. In addition, this study provides compelling morphological evidence explaining the altered structure-function relationship in load-deprived healing connective tissue.

  13. Influence of particle size on the distributions of liposomes to atherosclerotic lesions in mice.

    Science.gov (United States)

    Chono, Sumio; Tauchi, Yoshihiko; Morimoto, Kazuhiro

    2006-01-01

    In order to confirm the efficacy of liposomes as a drug carrier for atherosclerotic therapy, the influence of particle size on the distribution of liposomes to atherosclerotic lesions in mice was investigated. In brief, liposomes of three different particle sizes (500, 200, and 70 nm) were prepared, and the uptake of liposomes by the macrophages and foam cells in vitro and the biodistributions of liposomes administered intravenously to atherogenic mice in vivo were examined. The uptake by the macrophages and foam cells increased with the increase in particle size. Although the elimination rate from the blood circulation and the hepatic and splenic distribution increased with the increase in particle size in atherogenic mice, the aortic distribution was independent of the particle size. The aortic distribution of 200 nm liposomes was the highest in comparison with the other sizes. Surprisingly, the aortic distribution of liposomes in vivo did not correspond with the uptake by macrophages and foam cells in vitro. These results suggest that there is an optimal size for the distribution of liposomes to atherosclerotic lesions.

  14. Fluorescence imaging of macrophages in atherosclerotic plaques using plasmonic gold nanorose

    Science.gov (United States)

    Wang, Tianyi; Sapozhnikova, Veronika; Mancuso, J. Jacob; Willsey, Brian; Qiu, Jinze; Ma, Li L.; Li, Xiankai; Johnston, Keith P.; Feldman, Marc D.; Milner, Thomas E.

    2011-03-01

    Macrophages are one of the most important cell types involved in the progression of atherosclerosis which can lead to myocardial infarction. To detect macrophages in atherosclerotic plaques, plasmonic gold nanorose is introduced as a nontoxic contrast agent for fluorescence imaging. We report macrophage cell culture and ex vivo tissue studies to visualize macrophages targeted by nanorose using scanning confocal microscopy. Atherosclerotic lesions were created in the aorta of a New Zealand white rabbit model subjected to a high cholesterol diet and double balloon injury. The rabbit was injected with nanoroses coated with dextran. A HeNe laser at 633 nm was used as an excitation light source and a acousto-optical beam splitter was utilized to collect fluorescence emission in 650-760 nm spectral range. Results of scanning confocal microscopy of macrophage cell culture and ex vivo tissue showed that nanoroses produce a strong fluorescence signal. The presence of nanorose in ex vivo tissue was further confirmed by photothermal wave imaging. These results suggest that scanning confocal microscopy can identify the presence and location of nanorose-loaded macrophages in atherosclerotic plaques.

  15. Ophthalmic masquerades of the atherosclerotic carotids

    Directory of Open Access Journals (Sweden)

    Anupriya Arthur

    2014-01-01

    Full Text Available Patients with carotid atherosclerosis can present with ophthalmic symptoms. These symptoms and signs can be due to retinal emboli, hypoperfusion of the retina and choroid, opening up of collateral channels, or chronic hypoperfusion of the globe (ocular ischemic syndrome. These pathological mechanisms can produce many interesting signs and a careful history can bring out important past symptoms pointing toward the carotid as the source of the patient′s presenting symptom. Such patients are at high risk for an ischemic stroke, especially in the subsequent few days following their first acute symptom. It is important for clinicians to be familiar with these ophthalmic symptoms and signs caused by carotid atherosclerosis for making an early diagnosis and to take appropriate measures to prevent a stroke. This review elaborates the clinical features, importance, and implications of various ophthalmic symptoms and signs resulting from atherosclerotic carotid artery disease.

  16. Engineered Biopolymeric Scaffolds for Chronic Wound Healing.

    Science.gov (United States)

    Dickinson, Laura E; Gerecht, Sharon

    2016-01-01

    Skin regeneration requires the coordinated integration of concomitant biological and molecular events in the extracellular wound environment during overlapping phases of inflammation, proliferation, and matrix remodeling. This process is highly efficient during normal wound healing. However, chronic wounds fail to progress through the ordered and reparative wound healing process and are unable to heal, requiring long-term treatment at high costs. There are many advanced skin substitutes, which mostly comprise bioactive dressings containing mammalian derived matrix components, and/or human cells, in clinical use. However, it is presently hypothesized that no treatment significantly outperforms the others. To address this unmet challenge, recent research has focused on developing innovative acellular biopolymeric scaffolds as more efficacious wound healing therapies. These biomaterial-based skin substitutes are precisely engineered and fine-tuned to recapitulate aspects of the wound healing milieu and target specific events in the wound healing cascade to facilitate complete skin repair with restored function and tissue integrity. This mini-review will provide a brief overview of chronic wound healing and current skin substitute treatment strategies while focusing on recent engineering approaches that regenerate skin using synthetic, biopolymeric scaffolds. We discuss key polymeric scaffold design criteria, including degradation, biocompatibility, and microstructure, and how they translate to inductive microenvironments that stimulate cell infiltration and vascularization to enhance chronic wound healing. As healthcare moves toward precision medicine-based strategies, the potential and therapeutic implications of synthetic, biopolymeric scaffolds as tunable treatment modalities for chronic wounds will be considered. PMID:27547189

  17. Atherosclerotic Aortic Plaques Detected by Transesophageal Echocardiography

    Institute of Scientific and Technical Information of China (English)

    赵云; 朱文玲; 倪超; 郭丽琳; 曾勇; 方理刚

    2002-01-01

    Objective To evaluate the predictive value of atherosclerotic aortic plaques in coronary artery disease (CAD) Methods In 50patients with suspected coronary artery disease, transesophageal echocardiography was performed to examine their thoracic aortas 2 weeks before or after coronary angiography. In the cases of coronary angiography studied, stenosis of the coronary artery ≥ 50 % was considered to be due to coronary artery disease,whereas the thickness of the intima ≥ 1.3 mm was taken to be the criteria for the presence of an atherosclerotic aortic plaque on the transesophageal echocardiographic test. Results Among the 50 patients, 37 cases were diagnosed as CAD and 13 cases were considered to be normal. The plaques of the thoracic aorta were observed in 34cases in the CAD group and 3 cases in the normal group. The sensitivity and specificity of aortic plaques for CAD were 91.9 % and 76.9%, respectively. The positive and negative predictive values of the aortic plaques for CAD were 91.9% and 76.9%, respectively. The accuracy was 88.0%. 80 percent of the patients with single- yes sel disease had thoracic aortic plaques, 92 percent of the patients with two-vessel disease and 100 percent of the patients with three-vessel disease had thoracic aortic plaques. There was a significant difference in the thickness of aortic intimas between the normal group and the CAD group. Conclusions Detectingatherosclerotic plaques in the thoracic aorta with transesophageal echocardiography may be of great value in predicting the presence and extent of coronary artery disease.

  18. Biological strategies to enhance rotator cuff healing.

    Science.gov (United States)

    Longo, Umile Giuseppe; Rizzello, Giacomo; Berton, Alessandra; Maltese, Ludovica; Fumo, Caterina; Khan, Wasim S; Denaro, Vincenzo

    2013-11-01

    Rotator cuff tear causes a high rate of morbidity. After surgical repair, the presence of a scar tissue reduces tendon biomechanical properties. Emerging strategies for enhancing tendon healing are growth factors, cytokines, gene therapy and tissue engineering. However their efficacy has to be proved. Growth factors help the process of tendon healing by aiding cells chemotaxis, differentiation and proliferation. Numerous growth factors, including the bone morphogenetic proteins and platelet-derived growth factor can be found during the early healing process of a rotator cuff repair. Growth factors are delivered to the repair site using tissue-engineered scaffolding, coated sutures, or dissolved in a fibrin sealant. Platelet-rich plasma is an autologous concentration of platelets and contains an high density of growth factors. There is some evidence that platelet-rich plasma may improve pain and recovery of function in a short time period, but it does not improve healing rates in rotator cuff. Thus the routine use of platelet-rich plasma in rotator cuff repair is not recommended. The addition of mesenchymal stem cells to scaffolds can lead to the production of a better quality healing tissue. Gene therapy is a gene transfer from a cell into another, in order to over-express the gene required. In this way, cultures of stem cells can over-express growth factors. Better understanding of the mechanisms of physiological tendon healing can promote the correct use of these new biological therapies for a better healing tissue.

  19. Vasculogenic Cytokines in Wound Healing

    Directory of Open Access Journals (Sweden)

    Victor W. Wong

    2013-01-01

    Full Text Available Chronic wounds represent a growing healthcare burden that particularly afflicts aged, diabetic, vasculopathic, and obese patients. Studies have shown that nonhealing wounds are characterized by dysregulated cytokine networks that impair blood vessel formation. Two distinct forms of neovascularization have been described: vasculogenesis (driven by bone-marrow-derived circulating endothelial progenitor cells and angiogenesis (local endothelial cell sprouting from existing vasculature. Researchers have traditionally focused on angiogenesis but defects in vasculogenesis are increasingly recognized to impact diseases including wound healing. A more comprehensive understanding of vasculogenic cytokine networks may facilitate the development of novel strategies to treat recalcitrant wounds. Further, the clinical success of endothelial progenitor cell-based therapies will depend not only on the delivery of the cells themselves but also on the appropriate cytokine milieu to promote tissue regeneration. This paper will highlight major cytokines involved in vasculogenesis within the context of cutaneous wound healing.

  20. Evaluation of recombinant endostatin in the treatment of atherosclerotic plaques and neovascularization in rabbits*

    OpenAIRE

    Mao, Wei; Kong, Jing; Dai, Jin; Huang, Zhao-quan; Wang, Dong-zhi; Ni, Gui-bao; Chen, Min-Li

    2010-01-01

    Objective: Atherosclerotic plaques and neovascularization play an important role in the course of coronary atherosclerosis. This study evaluated the effect of recombinant endostatin on experimental atherosclerotic plaques and neovascularization in rabbits. Methods: Eighteen healthy male rabbits were divided into three groups: control group, atherosclerotic model group, and recombinant endostatin treated group. The atherosclerotic model was established via a high-cholesterol diet after balloon...

  1. IgM antibody level against proinflammatory bacterial peptidoglycan is inversely correlated with extent of atherosclerotic disease

    NARCIS (Netherlands)

    M.M.O. Nijhuis; Y. van der Graaf (Yolanda); M.J. Melief; A.H. Schoneveld (Arjan); D.P.V. de Kleijn (Dominique); J.D. Laman (Jon); G. Pasterkamp (Gerard)

    2004-01-01

    textabstractObjective: Atherosclerosis may lead to acute clinical events by rupture of a vulnerable atherosclerotic plaque. Previously, we demonstrated that peptidoglycan (PGN), a major cell wall component of gram-positive bacteria that induces production of proinflammatory cytokines through TLR2 an

  2. 间充质干细胞促进创面愈合机制的研究进展%Advances in the mechanism of mesenchymal stem cells in promoting wound healing

    Institute of Scientific and Technical Information of China (English)

    朱文静; 孙浩博; 吕国忠

    2015-01-01

    Mesenchymal stem cells possess the ability of self-renewal and multiple differentiation potential, thus exert immunomodulatory effect during tissue repair.Mesenchymal stem cells can stimulate angiogenesis and promote tissue repair through transdifferentiation and secreting a variety of growth factors and cytokines.This review outlines the advances in the mechanism of mesenchymal stem cells in promoting wound healing, including alleviation of inflammatory response, induction of angiogenesis, and promotion of migration of mesenchymal stem cells to the site of tissue injury.

  3. Fast and safe fabrication of a free-standing chitosan/alginate nanomembrane to promote stem cell delivery and wound healing

    Science.gov (United States)

    Kong, Yi; Xu, Rui; Darabi, Mohammad Ali; Zhong, Wen; Luo, Gaoxing; Xing, Malcolm MQ; Wu, Jun

    2016-01-01

    Polymeric ultrathin membranes that are compatible with cells offer tremendous advantages for tissue engineering. In this article, we report a free-standing nanomembrane that was developed using a layer-by-layer self-assembly technique with a safe and sacrificial substrate method. After ionization, two oppositely charged polyelectrolytes, alginate and chitosan, were alternately deposited on a substrate of a solidified gelatin block to form an ultrathin nanomembrane. The space between the two adjacent layers was ∼200 nm. The thickness of the nanomembrane was proportional to the number of layers. The temperature-sensitive gelatin gel served as a sacrificial template at 37°C. The free-standing nanomembrane promoted bone marrow stem cell adhesion and proliferation. Fluorescence-activated cell sorting was used to analyze green-fluorescent-protein-positive mesenchymal stem cells from the wounds, which showed a significantly high survival and proliferation from the nanomembrane when cells were transplanted to mouse dorsal skin that had a full-thickness burn. The bone-marrow-stem-cell-loaded nanomembrane also accelerated wound contraction and epidermalization. Therefore, this methodology provides a fast and facile approach to construct free-standing ultrathin scaffolds for tissue engineering. The biocompatibility and free-standing nature of the fabricated nanomembrane may be particularly useful for stem cell delivery and wound healing. PMID:27354789

  4. Fast and safe fabrication of a free-standing chitosan/alginate nanomembrane to promote stem cell delivery and wound healing.

    Science.gov (United States)

    Kong, Yi; Xu, Rui; Darabi, Mohammad Ali; Zhong, Wen; Luo, Gaoxing; Xing, Malcolm Mq; Wu, Jun

    2016-01-01

    Polymeric ultrathin membranes that are compatible with cells offer tremendous advantages for tissue engineering. In this article, we report a free-standing nanomembrane that was developed using a layer-by-layer self-assembly technique with a safe and sacrificial substrate method. After ionization, two oppositely charged polyelectrolytes, alginate and chitosan, were alternately deposited on a substrate of a solidified gelatin block to form an ultrathin nanomembrane. The space between the two adjacent layers was ∼200 nm. The thickness of the nanomembrane was proportional to the number of layers. The temperature-sensitive gelatin gel served as a sacrificial template at 37°C. The free-standing nanomembrane promoted bone marrow stem cell adhesion and proliferation. Fluorescence-activated cell sorting was used to analyze green-fluorescent-protein-positive mesenchymal stem cells from the wounds, which showed a significantly high survival and proliferation from the nanomembrane when cells were transplanted to mouse dorsal skin that had a full-thickness burn. The bone-marrow-stem-cell-loaded nanomembrane also accelerated wound contraction and epidermalization. Therefore, this methodology provides a fast and facile approach to construct free-standing ultrathin scaffolds for tissue engineering. The biocompatibility and free-standing nature of the fabricated nanomembrane may be particularly useful for stem cell delivery and wound healing. PMID:27354789

  5. Detecting microcalcifications in atherosclerotic plaques by a simple trichromic staining method for epoxy embedded carotid endarterectomies

    Science.gov (United States)

    Relucenti, M.; Heyn, R.; Petruzziello, L.; Pugliese, G.; Taurino, M.; Familiari, G.

    2010-01-01

    Atherosclerotic plaques have a high probability of undergoing rapid progression to stenosis, becoming responsible of acute coronary syndrome or stroke. Microcalcifications may act as enhancers of atherosclerotic plaque vulnerability. Considering that calcifications with a diameter smalller than 10 µm in paraffin embedded tissue are rather difficult to detect, our aim was to analyze microcalcifications on semithin sections from epoxy resin embedded samples of carotid endarterectomies using an original trichromic stain (methylene blue-azur B - basic fuchsine - alizarin red). We have compared samples stained either with our method, methylene blue-azur B alone or with Von Kossa staining, and methylene blue-azur B -basic fuchsine alone or with Von Kossa staining. Our method resulted to be simple and fast (ca. 2 min), it gives a sharp general contrast for all structures and allows to easy identify collagen and elastin. In addition, gray-green colour associated to intracellular lipid droplets evidences foam cells, which are particularly abundant in endarterectomies samples. Mast cells and their metachromatic granules are also well recognized. Calcifications over 0,5 µm are clearly recognizable. In conclusion, microcalcifications are clearly distinguished from the extracellular matrix in spite of their reduced dimensions. Methylene blue-azur B-basic fuchsine-alizarin red method is easy to use, reproducible, and is particularly suitable for the identification of microcalcifications in the morphological analysis of atherosclerotic plaques. PMID:20819772

  6. Detecting microcalcifications in atherosclerotic plaques by a simple trichromic staining method for epoxy embedded carotid endarterectomies

    Directory of Open Access Journals (Sweden)

    G. Familiari

    2010-09-01

    Full Text Available Atherosclerotic plaques have a high probability of undergoing rapid progression to stenosis, becoming responsible of acute coronary syndrome or stroke. Microcalcifications may act as enhancers of atherosclerotic plaque vulnerability. Considering that calcifications with a diameter smalller than 10 mm in paraffin embedded tissue are rather difficult to detect, our aim was to analyze microcalcifications on semithin sections from epoxy resin embedded samples of carotid endarterectomies using an original trichromic stain (methylene blue- azur B - basic fuchsine - alizarin red. We have compared samples stained either with our method, methylene blue-azur B alone or with Von Kossa staining, and methylene blue-azur B -basic fuchsine alone or with Von Kossa staining. Our method resulted to be simple and fast (ca. 2 min, it gives a sharp general contrast for all structures and allows to easy identify collagen and elastin. In addition, gray-green colour associated to intracellular lipid droplets evidences foam cells, which are particularly abundant in endarterectomies samples. Mast cells and their metachromatic granules are also well recognized. Calcifications over 0,5 mm are clearly recognizable. In conclusion, microcalcifications are clearly distinguished from the extracellular matrix in spite of their reduced dimensions. Methylene blue-azur B-basic fuchsine-alizarin red method is easy to use, reproducible, and is particularly suitable for the identification of microcalcifications in the morphological analysis of atherosclerotic plaques.

  7. Irradiation of existing atherosclerotic lesions increased inflammation by favoring pro-inflammatory macrophages

    International Nuclear Information System (INIS)

    Background and purpose: Recent studies have shown an increased incidence of localized atherosclerosis and subsequent cardiovascular events in cancer patients treated with thoracic radiotherapy. We previously demonstrated that irradiation accelerated the development of atherosclerosis and predisposed to an inflammatory plaque phenotype in young hypercholesterolemic ApoE−/− mice. However, as older cancer patients already have early or advanced stages of atherosclerosis at the time of radiotherapy, we investigated the effects of irradiation on the progression of existing atherosclerotic lesions in vivo. Material and methods: ApoE−/− mice (28 weeks old) received local irradiation with 14 or 0 Gy (sham-treated) at the aortic arch and were examined after 4 and 12 weeks for atherosclerotic lesions, plaque size and phenotype. Moreover, we investigated the impact of irradiation on macrophage phenotype (pro- or anti-inflammatory) and function (efferocytotic capacity, i.e. clearance of apoptotic cells) in vitro. Results: Irradiation of existing lesions in the aortic arch resulted in smaller, macrophage-rich plaques with intraplaque hemorrhage and increased apoptosis. In keeping with the latter, in vitro studies revealed augmented polarization toward pro-inflammatory macrophages after irradiation and reduced efferocytosis by anti-inflammatory macrophages. In addition, considerably more lesions in irradiated mice were enriched in pro-inflammatory macrophages. Conclusions: Irradiation of existing atherosclerotic lesions led to smaller but more inflamed plaques, with increased numbers of apoptotic cells, most likely due to a shift toward pro-inflammatory macrophages in the plaque

  8. A Proteomic Focus on the Alterations Occurring at the Human Atherosclerotic Coronary Intima*

    Science.gov (United States)

    de la Cuesta, Fernando; Alvarez-Llamas, Gloria; Maroto, Aroa S.; Donado, Alicia; Zubiri, Irene; Posada, Maria; Padial, Luis R.; Pinto, Angel G.; Barderas, Maria G.; Vivanco, Fernando

    2011-01-01

    Coronary atherosclerosis still represents the major cause of mortality in western societies. Initiation of atherosclerosis occurs within the intima, where major histological and molecular changes are produced during pathogenesis. So far, proteomic analysis of the atherome plaque has been mainly tackled by the analysis of the entire tissue, which may be a challenging approach because of the great complexity of this sample in terms of layers and cell type composition. Based on this, we aimed to study the intimal proteome from the human atherosclerotic coronary artery. For this purpose, we analyzed the intimal layer from human atherosclerotic coronaries, which were isolated by laser microdissection, and compared with those from preatherosclerotic coronary and radial arteries, using a two-dimensional Differential-In-Gel-Electrophoresis (DIGE) approach. Results have pointed out 13 proteins to be altered (seven up-regulated and six down-regulated), which are implicated in the migrative capacity of vascular smooth muscle cells, extracellular matrix composition, coagulation, apoptosis, heat shock response, and intraplaque hemorrhage deposition. Among these, three proteins (annexin 4, myosin regulatory light 2, smooth muscle isoform, and ferritin light chain) constitute novel atherosclerotic coronary intima proteins, because they were not previously identified at this human coronary layer. For this reason, these novel proteins were validated by immunohistochemistry, together with hemoglobin and vimentin, in an independent cohort of arteries. PMID:21248247

  9. A proteomic focus on the alterations occurring at the human atherosclerotic coronary intima.

    Science.gov (United States)

    de la Cuesta, Fernando; Alvarez-Llamas, Gloria; Maroto, Aroa S; Donado, Alicia; Zubiri, Irene; Posada, Maria; Padial, Luis R; Pinto, Angel G; Barderas, Maria G; Vivanco, Fernando

    2011-04-01

    Coronary atherosclerosis still represents the major cause of mortality in western societies. Initiation of atherosclerosis occurs within the intima, where major histological and molecular changes are produced during pathogenesis. So far, proteomic analysis of the atherome plaque has been mainly tackled by the analysis of the entire tissue, which may be a challenging approach because of the great complexity of this sample in terms of layers and cell type composition. Based on this, we aimed to study the intimal proteome from the human atherosclerotic coronary artery. For this purpose, we analyzed the intimal layer from human atherosclerotic coronaries, which were isolated by laser microdissection, and compared with those from preatherosclerotic coronary and radial arteries, using a two-dimensional Differential-In-Gel-Electrophoresis (DIGE) approach. Results have pointed out 13 proteins to be altered (seven up-regulated and six down-regulated), which are implicated in the migrative capacity of vascular smooth muscle cells, extracellular matrix composition, coagulation, apoptosis, heat shock response, and intraplaque hemorrhage deposition. Among these, three proteins (annexin 4, myosin regulatory light 2, smooth muscle isoform, and ferritin light chain) constitute novel atherosclerotic coronary intima proteins, because they were not previously identified at this human coronary layer. For this reason, these novel proteins were validated by immunohistochemistry, together with hemoglobin and vimentin, in an independent cohort of arteries. PMID:21248247

  10. The Effect of Conditioned Media of Adipose-Derived Stem Cells on Wound Healing after Ablative Fractional Carbon Dioxide Laser Resurfacing

    Directory of Open Access Journals (Sweden)

    Bing-Rong Zhou

    2013-01-01

    Full Text Available Objective. To evaluate the benefits of conditioned medium of Adipose-derived stem cells (ADSC-CM on wound healing after fractional carbon dioxide laser resurfacing (FxCR on human skin. Materials and Methods. Nineteen subjects were treated with FxCR on the bilateral inner arms. ADSC-CM was applied on FxCR site of one randomly selected arm. Transepidermal water loss (TEWL, skin color, and gross-elasticity of FxCR site on both arms were measured. Skin samples were taken by biopsy from three subjects 3 weeks after treatment for histopathological manifestations and mRNA expressions of procollagen types I and III, elastin genes were noted. Results. The index of erythema, melanin, and TEWL of the ADSC-CM-treated skin were significantly lower than those of the control side. The mRNA expression of type III procollagen in ADSC-CM-treated group at 3 weeks posttreatment was 2.6 times of that of the control group. Conclusion. Application of allograft ADSC-CM is an effective method for enhancing wound healing after FxCR, by reducing transient adverse effects such as erythema, hyperpigmentation, and increased TEWL.

  11. Prevalence and risk factors of atherosclerotic renal artery stenosis

    Institute of Scientific and Technical Information of China (English)

    严健华

    2013-01-01

    Objective To explore the prevalence and risk factors of atherosclerotic renal artery stenosis(ARAS) in patients undergoing coronary angiography.Methods A total of 2506 patients with suspected and known coronary

  12. Atherosclerotic lesions of supra-aortic arteries in diabetic patients

    OpenAIRE

    Vidjak, Vinko; Hebrang, Andrija; Brkljačić, Boris; Brajša, Mladen; Novačić, Karlo; Barada, Ante; Škopljanac, Andrija; Erdelez, Lidija; Crnčević, Maja; Kučan, Damir; Flegar-Meštrić, Zlata; Vrhovski-Hebrang, Danijela; Roić, Goran

    2007-01-01

    The aim of this prospective study was to determine the prevalence and localization of stenotic atherosclerotic lesions of supra-aortic arteries in diabetic patients according to age and sex. Angiograms obtained by digital subtraction angiography were analyzed in 150 diabetic patients (study group) and 150 non-diabetic patients (control group) with symptoms of cerebral ischemia. Diabetic patients were found to have a significantly higher prevalence of stenotic atherosclerotic lesions ...

  13. Stenting and cell technologies in the treatment of atherosclerotic renovascular hypertension Part 2. Effectiveness and safety of postnatal mobilized peripheral blood stem cell auto-transplantation into renal and vertebral arteries in ischemic kidney disease lasting over ten years

    NARCIS (Netherlands)

    Kharlamov, A. N.; Gabinsky, Ya. L.; Freydina, M. S.; Bos, E. K.; Naydanova, T. A.; Chernyshev, S. D.; Fadin, B. V.

    2008-01-01

    Aim. To assess effectiveness and safety of stem cell auto-transplantation (SCT) into renal and vertebral arteries among patients with renovascular hypertension (RVH) lasting over 10 years. Material and methods. Seventy-eight patients were randomized into main (MG, n=26) and placebo groups (PG, n=52)

  14. Enhancement of Tendon–Bone Healing for Anterior Cruciate Ligament (ACL Reconstruction Using Bone Marrow-Derived Mesenchymal Stem Cells Infected with BMP-2

    Directory of Open Access Journals (Sweden)

    Shiyi Chen

    2012-10-01

    Full Text Available At present, due to the growing attention focused on the issue of tendon–bone healing, we carried out an animal study of the use of genetic intervention combined with cell transplantation for the promotion of this process. Here, the efficacy of bone marrow stromal cells infected with bone morphogenetic protein-2 (BMP-2 on tendon–bone healing was determined. A eukaryotic expression vector containing the BMP-2 gene was constructed and bone marrow-derived mesenchymal stem cells (bMSCs were infected with a lentivirus. Next, we examined the viability of the infected cells and the mRNA and protein levels of BMP-2-infected bMSCs. Gastrocnemius tendons, gastrocnemius tendons wrapped by bMSCs infected with the control virus (bMSCs+Lv-Control, and gastrocnemius tendons wrapped by bMSCs infected with the recombinant BMP-2 virus (bMSCs+Lv-BMP-2 were used to reconstruct the anterior cruciate ligament (ACL in New Zealand white rabbits. Specimens from each group were harvested four and eight weeks postoperatively and evaluated using biomechanical and histological methods. The bMSCs were infected with the lentivirus at an efficiency close to 100%. The BMP-2 mRNA and protein levels in bMSCs were significantly increased after lentiviral infection. The bMSCs and BMP-2-infected bMSCs on the gastrocnemius tendon improved the biomechanical properties of the graft in the bone tunnel; specifically, bMSCs infected with BMP-2 had a positive effect on tendon–bone healing. In the four-week and eight-week groups, bMSCs+Lv-BMP-2 group exhibited significantly higher maximum loads of 29.3 ± 7.4 N and 45.5 ± 11.9 N, respectively, compared with the control group (19.9 ± 6.4 N and 21.9 ± 4.9 N (P = 0.041 and P = 0.001, respectively. In the eight-week groups, the stiffness of the bMSCs+Lv-BMP-2 group (32.5 ± 7.3 was significantly higher than that of the bMSCs+Lv-Control group (22.8 ± 7.4 or control groups (12.4 ± 6.0 (p = 0.036 and 0.001, respectively. Based on the

  15. Progression and regression of the atherosclerotic plaque.

    Science.gov (United States)

    de Feyter, P J; Vos, J; Deckers, J W

    1995-08-01

    In animals in which atherosclerosis was induced experimentally (by a high cholesterol diet) regression of the atherosclerotic lesion was demonstrated after serum cholesterol was reduced by cholesterol- lowering drugs or a low-fat diet. Whether regression of advanced coronary arterly lesions also takes place in humans after a similar intervention remains conjectural. However, several randomized studies, primarily employing lipid-lowering intervention or comprehensive changes in lifestyle, have demonstrated, using serial angiograms, that it is possible to achieve less progression, arrest or even (small) regression of atherosclerotic lesions. The lipid-lowering trials (NHBLI, CLAS, POSCH, FATS, SCOR and STARS) studied 1240 symptomatic patients, mostly men, with moderately elevated cholesterol levels and moderately severe angiographic-proven coronary artery disease. A variety of lipid-lowering drugs, in addition to a diet, were used over an intervention period ranging from 2 to 3 years. In all but one study (NHBLI), the progression of coronary atherosclerosis was less in the treated group, but regression was induced in only a few patients. The overall relative risk of progression of coronary atherosclerosis was 0 x 62 and 2 x 13, respectively. The induced angiographic differences were small and did not produce any significant haemodynamic benefit. The most important result was tht the disease process could be stabilized in the majority of patients. Three comprehensive lifestyle change trials (the Lifestyle Heart study, STARS and the Heidelberg Study) studied 183 patients, who were subjected to stress management, and/or intensive exercise, in addition to a low fat diet, over a period ranging from 1 to 3 years. All three trials demonstrated less progression, and more regression with overall relative risks of 0 x 40 and 2 x 35 respectively, in the intervention groups. Angiographic trials demonstrated that retardation or arrest of coronary atherosclerosis was possible

  16. Management of atherosclerotic renovascular disease after Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL).

    Science.gov (United States)

    Herrmann, Sandra M S; Saad, Ahmed; Textor, Stephen C

    2015-03-01

    Many patients with occlusive atherosclerotic renovascular disease (ARVD) may be managed effectively with medical therapy for several years without endovascular stenting, as demonstrated by randomized, prospective trials including the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial and the Stent Placement and Blood Pressure and Lipid-Lowering for the Prevention of Progression of Renal Dysfunction Caused by Atherosclerotic Ostial Stenosis of the Renal Artery (STAR) and ASTRAL. These trials share the limitation of excluding subsets of patients with high-risk clinical presentations, including episodic pulmonary edema and rapidly progressing renal failure and hypertension. Although hemodynamically significant, ARVD can reduce renal blood flow and glomerular filtration rate; adaptive mechanisms preserve both cortical and medullary oxygenation over a wide range of vascular occlusion. Progression of ARVD to severe vascular compromise eventually produces cortical hypoxia, however, associated with active inflammatory cytokine release and cellular infiltration of the renal parenchyma. In such cases ARVD produces a loss of glomerular filtration rate that no longer is reversible simply by restoring vessel patency with technically successful renal revascularization. Each of these trials reported adverse renal functional outcomes ranging between 16 and 22% over periods of 2-5 years of follow-up. Blood pressure control and medication adjustment may become more difficult with declining renal function and may prevent the use of angiotensin receptor blocker and angiotensin-converting enzyme inhibitors. The objective of this review is to evaluate the current management of ARVD for clinical nephrologists in the context of recent randomized clinical trials and experimental research. PMID:24723543

  17. Endogenous Bioactive Peptides as Potential Biomarkers for Atherosclerotic Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Tsutomu Hirano

    2012-04-01

    Full Text Available Cardiovascular disease is the leading cause of death worldwide, with high medical costs and rates of disability. It is therefore important to evaluate the use of cardiovascular biomarkers in the early diagnosis of coronary artery disease (CAD. We have screened a variety of recently identified bioactive peptides candidates in anticipation that they would allow detection of atherosclerotic CAD. Especially, we have focused on novel anti-atherogenic peptides as indicators and negative risk factors for CAD. In vitro, in vivo and clinical studies indicated that human adiponectin, heregulin-β1, glucagon-like peptide-1 (GLP-1, and salusin-α, peptides of 244, 71, 30, and 28 amino acids, respectively, attenuate the development and progression of atherosclerotic lesions by suppressing macrophage foam cell formation via down-regulation of acyl-coenzyme A: cholesterol acyltransferase-1. Circulating levels of these peptides in the blood are significantly decreased in patients with CAD compared to patients without CAD. Receiver operating characteristic analyses showed that salusin-α is a more useful biomarker, with better sensitivity and specificity, compared with the others for detecting CAD. Therefore, salusin-α, heregulin-β1, adiponectin, and/or GLP-1, alone or in various combinations, may be useful as biomarkers for atherosclerotic CAD.

  18. Bacterial wall products induce downregulation of vascular endothelial growth factor receptors on endothelial cells via a CD14-dependent mechanism: implications for surgical wound healing.

    LENUS (Irish Health Repository)

    Power, C

    2012-02-03

    INTRODUCTION: Vascular endothelial growth factor (VEGF) is a potent mitogenic cytokine which has been identified as the principal polypeptide growth factor influencing endothelial cell (EC) migration and proliferation. Ordered progression of these two processes is an absolute prerequisite for initiating and maintaining the proliferative phase of wound healing. The response of ECs to circulating VEGF is determined by, and directly proportional to, the functional expression of VEGF receptors (KDR\\/Flt-1) on the EC surface membrane. Systemic sepsis and wound contamination due to bacterial infection are associated with significant retardation of the proliferative phase of wound repair. The effects of the Gram-negative bacterial wall components lipopolysaccharide (LPS) and bacterial lipoprotein (BLP) on VEGF receptor function and expression are unknown and may represent an important biological mechanism predisposing to delayed wound healing in the presence of localized or systemic sepsis. MATERIALS AND METHODS: We designed a series of in vitro experiments investigating this phenomenon and its potential implications for infective wound repair. VEGF receptor density on ECs in the presence of LPS and BLP was assessed using flow cytometry. These parameters were assessed in hypoxic conditions as well as in normoxia. The contribution of CD14 was evaluated using recombinant human (rh) CD14. EC proliferation in response to VEGF was quantified in the presence and absence of LPS and BLP. RESULTS: Flow cytometric analysis revealed that LPS and BLP have profoundly repressive effects on VEGF receptor density in normoxic and, more pertinently, hypoxic conditions. The observed downregulation of constitutive and inducible VEGF receptor expression on ECs was not due to any directly cytotoxic effect of LPS and BLP on ECs, as measured by cell viability and apoptosis assays. We identified a pivotal role for soluble\\/serum CD14, a highly specific bacterial wall product receptor, in

  19. Biomarkers for wound healing and their evaluation.

    Science.gov (United States)

    Patel, S; Maheshwari, A; Chandra, A

    2016-01-01

    A biological marker (biomarker) is a substance used as an indicator of biological state. Advances in genomics, proteomics and molecular pathology have generated many candidate biomarkers with potential clinical value. Research has identified several cellular events and mediators associated with wound healing that can serve as biomarkers. Macrophages, neutrophils, fibroblasts and platelets release cytokines molecules including TNF-α, interleukins (ILs) and growth factors, of which platelet-derived growth factor (PDGF) holds the greatest importance. As a result, various white cells and connective tissue cells release both matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). Studies have demonstrated that IL-1, IL-6, and MMPs, levels above normal, and an abnormally high MMP/TIMP ratio are often present in non-healing wounds. Clinical examination of wounds for these mediators could predict which wounds will heal and which will not, suggesting use of these chemicals as biomarkers of wound healing. There is also evidence that the application of growth factors like PDGF will alleviate the recuperating process of chronic, non-healing wounds. Finding a specific biomarker for wound healing status would be a breakthrough in this field and helping treat impaired wound healing.

  20. Healing of experimentally created defects: a review

    DEFF Research Database (Denmark)

    Aaboe, M; Pinholt, E M; Hjørting-Hansen, E

    1995-01-01

    Within cranio-maxillofacial surgery and orthopedic surgery a bone graft or a bone substitute is required to recontour or assist bony healing in repair of osseous congenital deformities, or in repair of deformity due to trauma or to surgical excision after elimination of osseous disease processes...... of these materials questionable. Healing and degradation of alloplastic materials are inconsistent with subsequent restricted use. The principle of guided tissue regeneration excluding soft tissue cells from a certain area is not alone sufficient to insure complete bony healing. Recombinant bone morphogenetic...

  1. Ultrastructural characteristics of the vascular wall components of ruptured atherosclerotic abdominal aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Tanasković Irena

    2013-01-01

    Full Text Available The aim of this study was to determine the ultrastructural characteristics of cell populations and extracellular matrix components in the wall of ruptured atherosclerotic abdominal aortic aneurysm (AAA. We analyzed 20 samples of ruptured AAA. For orientation to the light microscopy, we used routine histochemical techniques by standard procedures. For ultrastructural analysis, we applied transmission electron microscopy (TEM. Our results have shown that ruptured AAA is characterized by the remains of an advanced atherosclerotic lesion in the intima followed by a complete absence of endothelial cells, the disruption of basal membrane and disruption of internal elastic lamina. On plaque margins as well as in the inner media we observed smooth muscle cells (SMCs that posses a euchromatic nucleus, a well-developed granulated endoplasmic reticulum around the nucleus and reduced myofilaments. The remains of the ruptured lipid core were acellular in all samples; however, on the lateral sides of ruptured plaque we observed a presence of two types of foam cells (FCs, spindle- and star-shaped. Fusiform FCs possess a well-differentiated basal lamina, caveolae and electron dense bodies, followed by a small number of lipid droplets in the cytoplasm. Star-shaped FCs contain a large number of lipid droplets and do not possess basal lamina. On the inner margins of the plaque, we observed a large number of cells undergoing apoptosis and necrosis, extracellular lipid droplets as well as a large number of lymphocytes. The media was thinned out with disorganized elastic lamellas, while the adventitia exhibited leukocyte infiltration. The presented results suggest that atherosclerotic plaque in ruptured AAA contains vascular SMC synthetic phenotype and two different types of FCs: some were derived from monocyte/macrophage lineage, while others were derived from SMCs of synthetic phenotype. The striking plaque hypocellularity was the result of apoptosis and necrosis

  2. Factors Affecting Wound Healing

    OpenAIRE

    Guo, S; DiPietro, L. A.

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutane...

  3. Lipid peroxidation-derived etheno-DNA adducts in human atherosclerotic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Jagadeesan [Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); De Flora, Silvio [Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa (Italy); Izzotti, Alberto [Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa (Italy); Bartsch, Helmut [Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany)]. E-mail: h.bartsch@dkfz.de

    2007-08-01

    Atherosclerosis and cancer are characterized by uncontrolled cell proliferation and share common risk factors, such as cigarette smoking, dietary habits and ageing. Growth of smooth muscle cells (SMCs) in atherosclerotic plaques may result from DNA damage, caused either by exogenous mutagens or by agents endogenously generated due to oxidative stress and lipid peroxidation (LPO). Hydroxy-2-nonenal (HNE), a major LPO product, binds covalently to cellular DNA to form the exocyclic etheno-DNA-base adducts, 1,N {sup 6}-ethenodeoxyadenine ({epsilon}dA) and 3,N {sup 4}-ethenodeoxycytosine ({epsilon}dC). By applying an ultrasensitive {sup 32}P-postlabeling-immunoaffinity method, {epsilon}dA and {epsilon}dC were quantified in abdominal aorta SMCs from 13 atherosclerotic patients and 3 non-smoking subjects without atherosclerotic lesions. The levels of etheno-adducts ranged for {epsilon}dA from 2.3 to 39.6/10{sup 8} dA and for {epsilon}dC from 10.7 to 157.7/10{sup 8} dC, with a high correlation between {epsilon}dA and {epsilon}dC (r = 0.84, P = 0.0001). Etheno-adduct levels were higher in atherosclerotic smokers than in ex-smokers for both {epsilon}dA (means 15.2 versus 7.3, P = 0.06) and {epsilon}dC (71.9 versus 51.6, not significant). {epsilon}dC levels were higher in either ex-smokers (P = 0.03) or smokers (P = 0.07) than in non-smokers. There was a poor correlation between either {epsilon}dA or {epsilon}dC and 8-hydroxy-2'-deoxyguanosine, whereas significant positive correlations were detected with the levels of several postlabeled bulky aromatic DNA adducts. In conclusion, two different types of DNA damage may be involved in atherosclerotic plaque formation and progression: (i) bulky aromatic compounds, to which aorta SMCs are chronically exposed in smokers, can either covalently bind to DNA, induce redox-cycling via quinone intermediates and/or activate local chronic inflammatory processes in the arterial wall; ii) this in turn leads to a self perpetuating

  4. A comprehensive review of advanced biopolymeric wound healing systems.

    Science.gov (United States)

    Mayet, Naeema; Choonara, Yahya E; Kumar, Pradeep; Tomar, Lomas K; Tyagi, Charu; Du Toit, Lisa C; Pillay, Viness

    2014-08-01

    Wound healing is a complex and dynamic process that involves the mediation of many initiators effective during the healing process such as cytokines, macrophages and fibroblasts. In addition, the defence mechanism of the body undergoes a step-by-step but continuous process known as the wound healing cascade to ensure optimal healing. Thus, when designing a wound healing system or dressing, it is pivotal that key factors such as optimal gaseous exchange, a moist wound environment, prevention of microbial activity and absorption of exudates are considered. A variety of wound dressings are available, however, not all meet the specific requirements of an ideal wound healing system to consider every aspect within the wound healing cascade. Recent research has focussed on the development of smart polymeric materials. Combining biopolymers that are crucial for wound healing may provide opportunities to synthesise matrices that are inductive to cells and that stimulate and trigger target cell responses crucial to the wound healing process. This review therefore outlines the processes involved in skin regeneration, optimal management and care required for wound treatment. It also assimilates, explores and discusses wound healing drug-delivery systems and nanotechnologies utilised for enhanced wound healing applications. PMID:24985412

  5. Proliferation of Keratinocytes Induced by Adipose-Derived Stem Cells on a Chitosan Scaffold and Its Role in Wound Healing, a Review

    OpenAIRE

    Gomathysankar, Sankaralakshmi; Halim, Ahmad Sukari; Yaacob, Nik Soriani

    2014-01-01

    In the field of tissue engineering and reconstruction, the development of efficient biomaterial is in high demand to achieve uncomplicated wound healing. Chronic wounds and excessive scarring are the major complications of tissue repair and, as this inadequate healing continues to increase, novel therapies and treatments for dysfunctional skin repair and reconstruction are important. This paper reviews the various aspects of the complications related to wound healing and focuses on chitosan b...

  6. Cellular events and biomarkers of wound healing

    OpenAIRE

    Shah Jumaat Mohd Yussof; Effat Omar; Pai, Dinker R.; Suneet Sood

    2012-01-01

    Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs) and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF) is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth f...

  7. Molecular Imaging of Healing After Myocardial Infarction

    OpenAIRE

    Naresh, Nivedita K; Ben-Mordechai, Tamar; Leor, Jonathan; Epstein, Frederick H

    2011-01-01

    The progression from acute myocardial infarction (MI) to heart failure continues to be a major cause of morbidity and mortality. Potential new therapies for improved infarct healing such as stem cells, gene therapy, and tissue engineering are being investigated. Noninvasive imaging plays a central role in the evaluation of MI and infarct healing, both clinically and in preclinical research. Traditionally, imaging has been used to assess cardiac structure, function, perfusion, and viability. H...

  8. Association of postalimentary lipemia with atherosclerotic manifestations

    Energy Technology Data Exchange (ETDEWEB)

    Tentor, J. [Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil); Nakamura, R.T. [Laboratório de Diagnóstico por Imagem, Campinas, SP (Brazil); Departamento de Radiologia, Universidade Estadual de Campinas, Campinas, SP (Brazil); Gidlund, M. [Laboratório de Imunofisiopatologia, Instituto de Ciências Biológicas, Universidade de São Paulo, São Paulo, SP (Brazil); Barros-Mazon, S. [Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil); Harada, L.M. [Laboratório de Lípides, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Zago, V.S.; Oba, J.F.; Faria, E.C. de [Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2012-08-10

    We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m{sup 2} body surface) at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT) was determined by Doppler ultrasound. The volunteers were classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male) and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP (negative) and FFA (positive). This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory.

  9. Local transplantation of ex vivo expanded bone marrow-derived CD34-positive cells accelerates fracture healing.

    Science.gov (United States)

    Kawakami, Yohei; Ii, Masaaki; Alev, Cantas; Kawamoto, Atsuhiko; Matsumoto, Tomoyuki; Kuroda, Ryosuke; Shoji, Taro; Fukui, Tomoaki; Masuda, Haruchika; Akimaru, Hiroshi; Mifune, Yutaka; Kuroda, Tomoya; Horii, Miki; Yokoyama, Ayumi; Kurosaka, Masahiro; Asahara, Takayuki

    2012-01-01

    Transplantation of bone marrow (BM) CD34(+) cells, an endothelial/hematopoietic progenitor-enriched cell population, has shown therapeutic efficiency in the treatment of ischemic diseases enhancing neovascularization. However, the number of CD34(+) cells obtained from bone marrow is not sufficient for routine clinical application. To overcome this issue, we developed a more efficient and clinically applicable CD34(+) cell expansion method. Seven-day ex vivo expansion culture of BM CD34(+) cells with a cocktail of five growth factors containing VEGF, SCF, IL-6, Flt-3 ligand, and TPO resulted in reproducible more than 20-fold increase in cell number. The favorable effect of the local transplantation of culture expanded (cEx)-BM CD34(+) cells on rat unhealing fractures was equivalent or higher than that of nonexpanded (fresh) BM CD34(+) cells exhibiting sufficient therapeutic outcome with frequent vasculogenic/osteogenic differentiation of transplanted cEx-BM CD34(+) cells and fresh BM CD34(+) cells as well as intrinsic enhancement of angiogenesis/osteogenesis at the treated fracture sites. Specifically, cEx-BM CD34(+) cell treatment demonstrated the best blood flow recovery at fracture sites compared with the nonexpanded BM CD34(+) cells. In vitro, cEx-BM CD34(+) cells showed higher colony/tube-forming capacity than nonexpanded BM CD34(+) cells. Both cells demonstrated differentiation potential into osteoblasts. Since fresh BM CD34(+) cells can be easily collected from fracture sites at the time of primary operation and stored for future use, autologous cEx-BM CD34(+) cell transplantation would be not only a simple but also a promising therapeutic strategy for unhealing fractures in the field of orthopedic trauma surgery.

  10. Self-formed grain boundary healing layer for highly efficient CH3 NH3 PbI3 perovskite solar cells

    Science.gov (United States)

    Son, Dae-Yong; Lee, Jin-Wook; Choi, Yung Ji; Jang, In-Hyuk; Lee, Seonhee; Yoo, Pil J.; Shin, Hyunjung; Ahn, Namyoung; Choi, Mansoo; Kim, Dongho; Park, Nam-Gyu

    2016-07-01

    Perovskite solar cells have attracted significant research efforts due to their remarkable performance, with certified power conversion efficiency now reaching 22%. Solution-processed perovskite thin films are polycrystalline, and grain boundaries are thought to be responsible for causing recombination and trapping of charge carriers. Here we report an effective and reproducible way of treating grain boundaries in CH3NH3PbI3 films deposited by means of a Lewis acid–base adduct approach. We show by high-resolution transmission electron microscopy lattice images that adding 6 mol% excess CH3NH3I to the precursor solution resulted in a CH3NH3I layer forming at the grain boundaries. This layer is responsible for suppressing non-radiative recombination and improving hole and electron extraction at the grain boundaries by forming highly ionic-conducting pathways. We report an average power conversion efficiency of 20.1% over 50 cells (best cell at 20.4%) together with significantly reduced current–voltage hysteresis achieved by this grain boundary healing process.

  11. Atherosclerotic Renal Artery Stenosis and Hypertension: Pragmatism, Pitfalls, and Perspectives.

    Science.gov (United States)

    Bavishi, Chirag; de Leeuw, Peter W; Messerli, Franz H

    2016-06-01

    For many years and even decades, a diagnostic work-up to look for a secondary form of hypertension, particularly of renovascular origin, has been a central tenet in medicine. Atherosclerotic renal artery stenosis is considered the most common cause of renovascular hypertension. However, advances in understanding the complex pathophysiology of this condition and the recently documented futility of renal revascularization bring into question whether atherosclerotic renal artery stenosis truly causes "renovascular hypertension." From a clinical point of view, a clear distinction should be made between hypertension associated with atherosclerotic renal artery stenosis and hypertension caused by renal artery stenosis-induced activation of the renin-angiotensin-aldosterone system. Most patients with atherosclerotic renal artery stenosis do not have a form of hypertension that is remediable or improved by angioplasty; to expose them to the cost, inconvenience, and risk of a diagnostic work-up add up to little more than a wild goose chase. However, with very few exceptions, medical therapy with antihypertensives and statins remains the cornerstone for the management of patients with atherosclerotic renal artery stenosis and hypertension. PMID:26522797

  12. Insulin inhibits inflammation and promotes atherosclerotic plaque stability via PI3K-Akt pathway activation.

    Science.gov (United States)

    Yan, Hao; Ma, Ying; Li, Yan; Zheng, Xiaohui; Lv, Ping; Zhang, Yuan; Li, Jia; Ma, Meijuan; Zhang, Le; Li, Congye; Zhang, Rongqing; Gao, Feng; Wang, Haichang; Tao, Ling

    2016-02-01

    Toll-like receptor (TLR) 4 induced inflammation was reported to play an important role in atherosclerotic plaque stability. Recent studies indicated that insulin could inhibit inflammation by activating phosphatidylinositol 3-kinase-Akt-dependent (PI3K-Akt) signaling pathway. In the current study, we hypothesized that insulin would inhibit TLR4 induced inflammation via promoting PI3K-Akt activation, thus enhancing the stabilization of atherosclerotic plaques. In order to mimic the process of plaque formation, monocyte-macrophage lineage RAW264.7 were cultured and induced to form foam cells by oxidized LDL (ox-LDL). Oil red O staining results showed that insulin significantly restrained ox-LDL-induced foam cell formation. Analysis of inflammatory reaction during foam cell formation indicated that insulin significantly down-regulated the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6 levels, inhibited TLR4, myeloid differentiation primary response gene (MyD) 88 and nuclear factor (NF)-κB. Further mechanism analysis showed that pretreating with the PI3K blocker, wortmannin dramatically dampened the insulin-induced up-regulation of pAkt expression. Additionally, blockade of PI3K-Akt signaling also dampened the immunosuppression effect brought by insulin. Following the construction of a rodent atherosclerosis model, pretreatment of insulin resulted in an evident decrease in lipid deposition of the blood vessel wall, serum levels of TNF-α and IL-6, and numbers of infiltrated macrophages and foam cells. Taken together, these results suggested that insulin might inhibit inflammation and promote atherosclerotic plaque stability via the PI3K-Akt pathway by targeting TLR4-MyD88-NF-κB signaling. Our findings may provide a potential target for the prevention of cardiovascular disease. PMID:26681144

  13. Cationic star-shaped polymer as an siRNA carrier for reducing MMP-9 expression in skin fibroblast cells and promoting wound healing in diabetic rats

    Directory of Open Access Journals (Sweden)

    Li N

    2014-07-01

    Full Text Available Na Li,1,* Heng-Cong Luo,1,* Chuan Yang,1 Jun-Jie Deng,2 Meng Ren,1 Xiao-Ying Xie,1 Diao-Zhu Lin,1 Li Yan,1 Li-Ming Zhang2 1Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2DSAPM Lab and PCFM Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Excessive expression of matrix metalloproteinase-9 (MMP-9 is deleterious to the cutaneous wound-healing process in the context of diabetes. The aim of the present study was to explore whether a cationic star-shaped polymer consisting of ß-cyclodextrin (ß-CD core and poly(amidoamine dendron arms (ß-CD-[D3]7 could be used as the gene carrier of small interfering RNA (siRNA to reduce MMP-9 expression for enhanced diabetic wound healing. Methods: The cytotoxicity of ß-CD-(D37 was investigated by 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay (MMT method in the rat CRL1213 skin fibroblast cell line. The transfection efficiency of ß-CD-(D37/MMP-9-small interfering RNA (siRNA complexes was determined by confocal microscopy and flow cytometry. Quantitative real time (RT polymerase chain reaction was performed to measure the gene expression of MMP-9 after the transfection by ß-CD-(D37/MMP-9-siRNA complexes. The ß-CD-(D37/MMP-9-siRNA complexes were injected on the wounds of streptozocin-induced diabetic rats. Wound closure was measured on days 4 and 7 post-wounding. Results: ß-CD-(D37 exhibited low cytotoxicity in fibroblast cells, and easily formed the complexes with MMP-9-siRNA. The ß-CD-(D37/MMP-9-siRNA complexes were readily taken up by fibroblast cells, resulting in the downregulation of MMP-9 gene expression (P<0.01. Animal experiments revealed that the treatment by ß-CD-(D37/MMP-9-siRNA complexes enhanced wound

  14. Current wound healing procedures and potential care.

    Science.gov (United States)

    Dreifke, Michael B; Jayasuriya, Amil A; Jayasuriya, Ambalangodage C

    2015-03-01

    In this review, we describe current and future potential wound healing treatments for acute and chronic wounds. The current wound healing approaches are based on autografts, allografts, and cultured epithelial autografts, and wound dressings based on biocompatible and biodegradable polymers. The Food and Drug Administration approved wound healing dressings based on several polymers including collagen, silicon, chitosan, and hyaluronic acid. The new potential therapeutic intervention for wound healing includes sustained delivery of growth factors, and siRNA delivery, targeting microRNA, and stem cell therapy. In addition, environment sensors can also potentially utilize to monitor and manage microenvironment at wound site. Sensors use optical, odor, pH, and hydration sensors to detect such characteristics as uric acid level, pH, protease level, and infection - all in the hopes of early detection of complications.

  15. Value of detection of atherosclerotic lesions using autologous labelled platelets

    Energy Technology Data Exchange (ETDEWEB)

    Sinzinger, H.; Silberbauer, K.; Fitscha, P.; Kaliman, J. (Vienna Univ. (Austria). 2. Medizinische Klinik; Vienna Univ. (Austria). Kardiologische Abt.; Allgem. Poliklinik, Vienna (Austria). 2. Medizinische Abteilung)

    1982-01-01

    In 44 patients with clinical signs of carotid artery stenosis a positive Doppler-ultrasound was obtained. In all patients the lesions were confirmed by angiography. In the patients labelling of autologous platelets with 111 Indium-oxine-sulphate was done in order to calculate the platelet half-life. In addition we tried to visualize the verified atherosclerotic lesions under a gamma-camera. In all patients the platelet half-life was significantly shortened in comparison to the controls. In none of the patients studied a visualization of the angiographically verified atherosclerotic lesions could be obtained. These findings point out, that only in recently developed and very severe atherosclerotic lesions the number of platelets deposed on the vascular surface is enough to allow gamma-camera imaging.

  16. High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis.

    Science.gov (United States)

    Wang, Yi; Qiu, Juhui; Luo, Shisui; Xie, Xiang; Zheng, Yiming; Zhang, Kang; Ye, Zhiyi; Liu, Wanqian; Gregersen, Hans; Wang, Guixue

    2016-12-01

    Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic strokes. Inhibition of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular grafts. Shear stress (SS) influences the formation and development of atherosclerosis. The current review focuses on the vulnerable plaques observed in the high shear stress (HSS) regions, which localizes at the proximal region of the plaque intruding into the lumen. The vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque formation. These results greatly challenge the established belief that low shear stress is important for expansive remodelling, which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions. PMID:27482467

  17. Induction of the Chemokines CCL3α, CCL3α and CCL5 in Atherosclerotic Patients

    Directory of Open Access Journals (Sweden)

    Alyaa Mousa

    2007-01-01

    Full Text Available Chemokines recruit immune cells to inflammatory sites and promote the process of inflammation. The role of these mediators in the disease process in atherosclerosis is not fully studied. The spontaneous mRNA expression and intracellular protein production of the potential inflammatory chemokines CCL3 and CCL3 (macrophage- inflammatory protein-1and ; CCR3 ligand and CCL5 (regulated upon activation, normal T cell expressed and secreted (RANTES; CCR5 ligand in atherosclerotic patients was examined together with the effects of the chlamydial antigen HSP60 and LPS on the gene expression and protein induction of these mediators. Detection of chemokine mRNA and protein levels was assessed by in situ hybridization and immunohistochemistry respectively. The examined chemokines were detected at significantly high levels on atherosclerotic patients compared to healthy controls at both mRNA and protein levels. Stimulation with HSP60 and LPS from Chlamydia pneumoniae (C. pneumoniae and E. coli showed increased numbers of CCL3, CCL3 and CCL5 mRNA expressing cells in patients compared to health controls. Protein translation of these chemokines was depicted in correspondence to the mRNA gene expression for all examined chemokines spontaneously and after stimulation with chlamydial HSP60 and LPS and E. coli LPS. Thus, the herein data demonstrate the induction of potential inflammatory chemokines in atherosclerotic patients and that bacterial antigens play a role in the immunopathologic events in this disease by generating more inflammatory mediators.

  18. 表皮干细胞在糖尿病伤口修复治疗中的作用%The role of epidermal stem cell on diabetic wound healing

    Institute of Scientific and Technical Information of China (English)

    杜娟; 刘雪来

    2016-01-01

    The epidermal stem cell was introduced briefly in this review.And then the spacial characteristics of diabetic wound healing were summarized.In this regards,we focus on the important role of epidermal stem cell in diabetic wound healing.At last,we outlook the research direction and clinical application of epidermal stem cell in diabetic wound.%本文概述表皮干细胞的生物学特点,总结糖尿病伤口的特殊性及不易愈合的原因,追踪表皮干细胞在糖尿病伤口修复中的研究进展,最后展望表皮干细胞技术对糖尿病皮肤伤口修复的研究方向.

  19. A wound healing model with sonographic monitoring.

    Science.gov (United States)

    Hoffmann, K; Winkler, K; el-Gammal, S; Altmeyer, P

    1993-05-01

    The methods used hitherto for quantification of skin repair processes only allow an examiner a two-dimensional assessment of superficial wound healing. With the recent advent of high frequency B-scan ultrasonography in dermatology it has become possible to follow the course of healing and evaluate the healing processes in deeper layers of the skin. In this investigation 80 patients received cryosurgery for treatment of basal cell carcinomas on the face or neck region. As the size of cryosurgical defects can be precisely controlled they are potentially useful as standardized wound healing models. The course of wound healing after cryosurgery using a digital ultrasound scanner (DUB 20, Taberna pro medicum, Lüneburg, Germany) was monitored. The usable depth of penetration of the echo signal is approximately 7 mm. The lateral resolution is approximately 200 microns, the axial resolution approximately 80 microns. The cryolesion and the repair processes were examined ultrasonographically and clinically over a period of at least 3 weeks or until the wound had completely healed. The depth of invasion and lateral extent of the basal cell carcinoma as well as the size of the induced cryolesion can be determined by ultrasound. The exudative phase after cryosurgery, with developing oedema and necrosis, can be quantified on the basis of the reduced reflectivity in the corium. The repair processes taking place in the region of necrosis can be visualized in the ultrasound scan. The ultrasonically monitored wound healing model which we have demonstrated is particularly suitable for investigating the efficacy of drugs which promote healing.

  20. Vapor and healing treatment for CH3NH3PbI3-xClx films toward large-area perovskite solar cells

    Science.gov (United States)

    Gouda, Laxman; Gottesman, Ronen; Tirosh, Shay; Haltzi, Eynav; Hu, Jiangang; Ginsburg, Adam; Keller, David A.; Bouhadana, Yaniv; Zaban, Arie

    2016-03-01

    Hybrid methyl-ammonium lead trihalide perovskites are promising low-cost materials for use in solar cells and other optoelectronic applications. With a certified photovoltaic conversion efficiency record of 20.1%, scale-up for commercial purposes is already underway. However, preparation of large-area perovskite films remains a challenge, and films of perovskites on large electrodes suffer from non-uniform performance. Thus, production and characterization of the lateral uniformity of large-area films is a crucial step towards scale-up of devices. In this paper, we present a reproducible method for improving the lateral uniformity and performance of large-area perovskite solar cells (32 cm2). The method is based on methyl-ammonium iodide (MAI) vapor treatment as a new step in the sequential deposition of perovskite films. Following the MAI vapor treatment, we used high throughput techniques to map the photovoltaic performance throughout the large-area device. The lateral uniformity and performance of all photovoltaic parameters (Voc, Jsc, Fill Factor, Photo-conversion efficiency) increased, with an overall improved photo-conversion efficiency of ~100% following a vapor treatment at 140 °C. Based on XRD and photoluminescence measurements, We propose that the MAI treatment promotes a ``healing effect'' to the perovskite film which increases the lateral uniformity across the large-area solar cell. Thus, the straightforward MAI vapor treatment is highly beneficial for large scale commercialization of perovskite solar cells, regardless of the specific deposition method.Hybrid methyl-ammonium lead trihalide perovskites are promising low-cost materials for use in solar cells and other optoelectronic applications. With a certified photovoltaic conversion efficiency record of 20.1%, scale-up for commercial purposes is already underway. However, preparation of large-area perovskite films remains a challenge, and films of perovskites on large electrodes suffer from non

  1. Complement deficiency promotes cutaneous wound healing in mice.

    Science.gov (United States)

    Rafail, Stavros; Kourtzelis, Ioannis; Foukas, Periklis G; Markiewski, Maciej M; DeAngelis, Robert A; Guariento, Mara; Ricklin, Daniel; Grice, Elizabeth A; Lambris, John D

    2015-02-01

    Wound healing is a complex homeostatic response to injury that engages numerous cellular activities, processes, and cell-to-cell interactions. The complement system, an intricate network of proteins with important roles in immune surveillance and homeostasis, has been implicated in many physiological processes; however, its role in wound healing remains largely unexplored. In this study, we employ a murine model of excisional cutaneous wound healing and show that C3(-/-) mice exhibit accelerated early stages of wound healing. Reconstitution of C3(-/-) mice with serum from C3(+/+) mice or purified human C3 abrogated the accelerated wound-healing phenotype. Wound histology of C3(-/-) mice revealed a reduction in inflammatory infiltrate compared with C3(+/+) mice. C3 deficiency also resulted in increased accumulation of mast cells and advanced angiogenesis. We further show that mice deficient in the downstream complement effector C5 exhibit a similar wound-healing phenotype, which is recapitulated in C5aR1(-/-) mice, but not C3aR(-/-) or C5aR2(-/-) mice. Taken together, these data suggest that C5a signaling through C5aR may in part play a pivotal role in recruitment and activation of inflammatory cells to the wound environment, which in turn could delay the early stages of cutaneous wound healing. These findings also suggest a previously underappreciated role for complement in wound healing, and may have therapeutic implications for conditions of delayed wound healing.

  2. Mechanoregulation of Wound Healing and Skin Homeostasis.

    Science.gov (United States)

    Rosińczuk, Joanna; Taradaj, Jakub; Dymarek, Robert; Sopel, Mirosław

    2016-01-01

    Basic and clinical studies on mechanobiology of cells and tissues point to the importance of mechanical forces in the process of skin regeneration and wound healing. These studies result in the development of new therapies that use mechanical force which supports effective healing. A better understanding of mechanobiology will make it possible to develop biomaterials with appropriate physical and chemical properties used to treat poorly healing wounds. In addition, it will make it possible to design devices precisely controlling wound mechanics and to individualize a therapy depending on the type, size, and anatomical location of the wound in specific patients, which will increase the clinical efficiency of the therapy. Linking mechanobiology with the science of biomaterials and nanotechnology will enable in the near future precise interference in abnormal cell signaling responsible for the proliferation, differentiation, cell death, and restoration of the biological balance. The objective of this study is to point to the importance of mechanobiology in regeneration of skin damage and wound healing. The study describes the influence of rigidity of extracellular matrix and special restrictions on cell physiology. The study also defines how and what mechanical changes influence tissue regeneration and wound healing. The influence of mechanical signals in the process of proliferation, differentiation, and skin regeneration is tagged in the study. PMID:27413744

  3. Mechanoregulation of Wound Healing and Skin Homeostasis

    Directory of Open Access Journals (Sweden)

    Joanna Rosińczuk

    2016-01-01

    Full Text Available Basic and clinical studies on mechanobiology of cells and tissues point to the importance of mechanical forces in the process of skin regeneration and wound healing. These studies result in the development of new therapies that use mechanical force which supports effective healing. A better understanding of mechanobiology will make it possible to develop biomaterials with appropriate physical and chemical properties used to treat poorly healing wounds. In addition, it will make it possible to design devices precisely controlling wound mechanics and to individualize a therapy depending on the type, size, and anatomical location of the wound in specific patients, which will increase the clinical efficiency of the therapy. Linking mechanobiology with the science of biomaterials and nanotechnology will enable in the near future precise interference in abnormal cell signaling responsible for the proliferation, differentiation, cell death, and restoration of the biological balance. The objective of this study is to point to the importance of mechanobiology in regeneration of skin damage and wound healing. The study describes the influence of rigidity of extracellular matrix and special restrictions on cell physiology. The study also defines how and what mechanical changes influence tissue regeneration and wound healing. The influence of mechanical signals in the process of proliferation, differentiation, and skin regeneration is tagged in the study.

  4. Hemostatic and Wound Healing Properties of Chromolaena odorata Leaf Extract

    OpenAIRE

    Seung Joon Baek; Wandee Gritsanapan; Kyung-Won Min; Jason Liggett; Xiaobo Zhang; Hataichanok Pandith

    2013-01-01

    Chromolaena odorata (L.) King and Robinson (Siam weed) extract has been used to stop bleeding and in wound healing in many tropical countries. However, its detailed mechanisms have not been elucidated. In this study, we examined the molecular mechanisms by which Siam weed extract (SWE) affected hemostatic and wound healing activities. SWE promoted Balb/c 3T3 fibroblast cell migration and proliferation. Subsequently, we found that heme oxygenase-1 (HO-1), the accelerating wound healing enzyme,...

  5. Inflammation and Neuropeptides: The Connection in Diabetic Wound Healing

    OpenAIRE

    Pradhan, Leena; Nabzdyk, Christoph; Andersen, Nicholas D.; LoGerfo, Frank W; Veves, Aristidis

    2009-01-01

    This article provides a broad overview of the interaction between neuropeptides and inflammatory mediators as it pertains to diabetic wound healing. Abnormal wound healing is a major complication of both type I and type II diabetes and is the most frequent cause of non-traumatic lower limb amputation. Wound healing requires the orchestrated integration of complex biological and molecular events. Inflammation, proliferation and migration of cells followed by angiogenesis and re-epithelization ...

  6. Safrole-2',3'-oxide induces atherosclerotic plaque vulnerability in apolipoprotein E-knockout mice.

    Science.gov (United States)

    Su, Le; Zhang, Haiyan; Zhao, Jing; Zhang, Shangli; Zhang, Yun; Zhao, Baoxiang; Miao, Junying

    2013-02-27

    Safrole-2',3'-oxide (SFO) is the major electrophilic metabolite of safrole (4-allyl-1, 2-methylenedioxybenzene), a natural plant constituent found in essential oils of numerous edible herbs and spices and in food containing these herbs, such as pesto sauce, cola beverages and bologna sausages. The effects of SFO in mammalian systems, especially the cardiovascular system, are little known. Disruption of vulnerable atherosclerotic plaques in atherosclerosis, a chronic inflammatory disease, is the main cause of cardiovascular events. In this study, we investigated SFO-induced atherosclerotic plaque vulnerability (possibility of rupture) in apolipoprotein E-knockout (apoE(-/-)) mice. Lipid area in vessel wall reached 59.8% in high dose SFO (SFO-HD) treated group, which is only 31.2% in control group. SFO treatment changed the lesion composition to an unstable phenotype, increased the number of apoptotic cells in plaque and the endothelium in plaques was damaged after SFO treatment. Furthermore, compared with control groups, the plaque endothelium level of p75(NTR) was 3-fold increased and the liver level of p75(NTR) was 17.4-fold increased by SFO-HD. Meanwhile, the serum level of KC (a functional homolog of IL-8 and the main proinflammatory alpha chemokine in mice) in apoE(-/-) mice was up to 357pg/ml in SFO-HD treated group. Thus, SFO contributes to the instability of atherosclerotic plaque in apoE(-/-) mice through activating p75(NTR) and IL-8 and cell apoptosis in plaque.

  7. Healing Childhood Trauma Worldwide

    Science.gov (United States)

    Kuban, Caelan

    2012-01-01

    Millions of the world's children are exposed to traumatic events and relationships every day. Whatever the cause, this overwhelming stress produces a host of unsettling symptoms and reactions. The author highlights six practical principles that undergird healing interventions.

  8. Organic semiconductors: Healing contact

    Science.gov (United States)

    Risko, Chad; Brédas, Jean-Luc

    2013-12-01

    Traps in organic semiconducting crystals are healed when a perfluoropolyether oil is deposited on the surface of these materials, thus making possible the detection of intrinsic features of charge-carrier transport in rubrene and tetracene.

  9. How wounds heal

    Science.gov (United States)

    ... PA: Mosby Elsevier; 2010: chap. 7. Richardson M. Acute wounds: an overview of the physiological healing process. Nursing Times . 2004; 100(4): 50. Von Der Heyde RL, Evans RB. Wound classification ...

  10. Hematopoietic Fas deficiency does not affect experimental atherosclerotic lesion formation despite inducing a proatherogenic state.

    Science.gov (United States)

    de Claro, R Angelo; Zhu, Xiaodong; Tang, Jingjing; Morgan-Stevenson, Vicki; Schwartz, Barbara R; Iwata, Akiko; Liles, W Conrad; Raines, Elaine W; Harlan, John M

    2011-06-01

    The Fas death receptor (CD95) is expressed on macrophages, smooth muscle cells, and T cells within atherosclerotic lesions. Given the dual roles of Fas in both apoptotic and nonapoptotic signaling, the aim of the present study was to test the effect of hematopoietic Fas deficiency on experimental atherosclerosis in low-density lipoprotein receptor-null mice (Ldlr(-/-)). Bone marrow from Fas(-/-) mice was used to reconstitute irradiated Ldlr(-/-) mice as a model for atherosclerosis. After 16 weeks on an 0.5% cholesterol diet, no differences were noted in brachiocephalic artery lesion size, cellularity, or vessel wall apoptosis. However, Ldlr(-/-) mice reconstituted with Fas(-/-) hematopoietic cells had elevated hyperlipidemia [80% increase, relative to wild-type (WT) controls; P < 0.001] and showed marked elevation of plasma levels of CXCL1/KC, CCL2/MCP-1, IL-6, IL-10, IL-12 subunit p70, and soluble Fas ligand (P < 0.01), as well as systemic microvascular inflammation. It was not possible to assess later stages of atherosclerosis because of increased mortality in Fas(-/-) bone marrow recipients. Our data indicate that hematopoietic Fas deficiency does not affect early atherosclerotic lesion development in Ldlr(-/-) mice.

  11. Diabetes and wound healing

    OpenAIRE

    Svendsen, Rikke; Irakunda, Gloire; Knudsen List, Karoline Cecilie; Sønderstup-Jensen, Marie; Hölmich Rosca, Mette Maria

    2014-01-01

    Diabetes is a disease where the glucose level in the blood is high, due to either insulin resistance, impaired insulin sensitivity or no insulin production. The high glucose level causes several complications, one of them being an impaired wound healing process, which might lead to chronic wounds, ulcers. Several factors play a role in the development of ulcers, and recent research indicates that microRNA might play a significant role in skin development and wound healing. The purpose of this...

  12. Clinical analysis of 132 patients with atherosclerotic renal artery stenosis

    Institute of Scientific and Technical Information of China (English)

    徐红

    2006-01-01

    Objective To evaluate the prognostic result of renal function on atherosclerotic renal artery stenosis (ARAS) patients after revascularization and medication therapy. Methods The clinical data of 132 AEIAS patients diagnosed by renal angiography were analysed. For comparing the differences of glomenilar filtration rate (GFR) be-

  13. ATHEROSCLEROTIC CARDIOVASCULAR DISEASE IN OLDER ADULTS WITH DIABETES MELLITUS

    OpenAIRE

    Barzilay, Joshua I.; Mukamal, Kenneth J.; Kizer, Jorge R.

    2014-01-01

    Diabetes Mellitus exerts a strong effect on atherosclerotic cardiovascular disease risk into older age (beyond ages 70 to 74 years). This effect is particularly noticeable with regard to coronary artery disease and cerebral microvascular disease. Thus Diabetes Mellitus in older age deserves the same careful medical attention as it does in middle age.

  14. Chemokine Receptor 7 Knockout Attenuates Atherosclerotic Plaque Development

    NARCIS (Netherlands)

    Luchtefeld, Maren; Grothusen, Christina; Gagalick, Andreas; Jagavelu, Kumaravelu; Schuett, Harald; Tietge, Uwe J. F.; Pabst, Oliver; Grote, Karsten; Drexler, Helmut; Foerster, Reinhold; Schieffer, Bernhard

    2010-01-01

    Background-Atherosclerosis is a systemic inflammatory disease characterized by the formation of atherosclerotic plaques. Both innate immunity and adaptive immunity contribute to atherogenesis, but the mode of interaction is poorly understood. Chemokine receptor 7 (CCR7) is critically involved in the

  15. Acute type II cryoglobulinaemic vasculitis mimicking atherosclerotic peripheral vascular disease.

    LENUS (Irish Health Repository)

    Saeed, A

    2012-01-31

    Atherosclerotic peripheral vascular disease is a common presenting cause for digital ischaemia in life long smokers. Acute severe Type II Cryoglobulinaemic vasculitis is a rare yet important cause, which may present with similar clinical features and which if undiagnosed may be rapidly fatal. Following the instigation of therapy with intravenous methylprednisolone and cyclophosphamide this patient made an excellent recovery.

  16. Atherosclerotic Plaque Destabilization in Mice: A Comparative Study.

    Directory of Open Access Journals (Sweden)

    Helene Hartwig

    Full Text Available Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.

  17. Using a Hydroquinone/Tretinoin-based Skin Care System Before and After Electrodesiccation and Curettage of Superficial Truncal Basal Cell Carcinoma: A Multicenter, Randomized, Investigator-blind, Controlled Study of Short-term Healing

    OpenAIRE

    David, Pariser; James, Spencer; Brian, Berman; Suzanne, Bruce; Lisa, Parr; Kenneth, Gross

    2009-01-01

    Objective: To evaluate the efficacy and tolerability of using a 4% hydroquinone/0.05% tretinoin skin care system compared with standard treatment of cleanser plus healing ointment to enhance aesthetic outcomes resulting from electrodesiccation and curettage treatment for superficial truncal basal cell carcinomas. Design: Multicenter, investigator-masked, randomized, parallel-group study. Patients received either the hydroquinone/tretinoin system or the standard treatment twice daily for three...

  18. Cross-reacting antibacterial auto-antibodies are produced within coronary atherosclerotic plaques of acute coronary syndrome patients.

    Directory of Open Access Journals (Sweden)

    Filippo Canducci

    Full Text Available Coronary atherosclerosis, the main condition predisposing to acute myocardial infarction, has an inflammatory component caused by stimuli that are yet unknown. We molecularly investigated the nature of the immune response within human coronary lesion in four coronary plaques obtained by endoluminal atherectomy from four patients. We constructed phage-display libraries containing the IgG1/kappa antibody fragments produced by B-lymphocytes present in each plaque. By immunoaffinity, we selected from these libraries a monoclonal antibody, arbitrarily named Fab7816, able to react both with coronary and carotid atherosclerotic tissue samples. We also demonstrated by confocal microscopy that this monoclonal antibody recognized human transgelin type 1, a cytoskeleton protein involved in atherogenesis, and that it co-localized with fibrocyte-like cells transgelin+, CD68+, CD45+ in human sections of coronary and carotid plaques. In vitro fibrocytes obtained by differentiating CD14+ cells isolated from peripheral blood mononuclear cells also interacted with Fab7816, thus supporting the hypothesis of a specific recognition of fibrocytes into the atherosclerotic lesions. Interestingly, the same antibody, cross-reacted with the outer membrane proteins of Proteus mirabilis and Klebsiella pneumoniae (and possibly with homologous proteins of other enterobacteriaceae present in the microbiota. From all the other three libraries, we were able to clone, by immunoaffinity selection, human monoclonal antibodies cross-reacting with bacterial outer membrane proteins and with transgelin. These findings demonstrated that in human atherosclerotic plaques a local cross-reactive immune response takes place.

  19. A degradable, bioactive, gelatinized alginate hydrogel to improve stem cell/growth factor delivery and facilitate healing after myocardial infarction.

    Science.gov (United States)

    Della Rocca, Domenico G; Willenberg, Bradley J; Ferreira, Leonardo F; Wate, Prateek S; Petersen, John W; Handberg, Eileen M; Zheng, Tong; Steindler, Dennis A; Terada, Naohiro; Batich, Christopher D; Byrne, Barry J; Pepine, Carl J

    2012-11-01

    Despite remarkable effectiveness of reperfusion and drug therapies to reduce morbidity and mortality following myocardial infarction (MI), many patients have debilitating symptoms and impaired left ventricular (LV) function highlighting the need for improved post-MI therapies. A promising concept currently under investigation is intramyocardial injection of high-water content, polymeric biomaterial gels (e.g., hydrogels) to modulate myocardial scar formation and LV adverse remodeling. We propose a degradable, bioactive hydrogel that forms a unique microstructure of continuous, parallel capillary-like channels (Capgel). We hypothesize that the innovative architecture and composition of Capgel can serve as a platform for endogenous cell recruitment and drug/cell delivery, therefore facilitating myocardial repair after MI.

  20. Heat Stress and Hormetin-Induced Hormesis in Human Cells: Effects on Aging, Wound Healing, Angiogenesis, and Differentiation

    OpenAIRE

    Rattan, Suresh I.S.; Fernandes, Ricardo A.; Demirovic, Dino; Dymek, Barbara; Lima, Cristovao F.

    2008-01-01

    Accumulation of molecular damage and increased molecular heterogeneity are hallmarks of cellular aging. Mild stress-induced hormesis can be an effective way for reducing the accumulation of molecular damage, and thus slowing down aging from within. We have shown that repeated mild heat stress (RMHS) has anti-aging effects on growth and various other cellular and biochemical characteristics of normal human skin fibroblasts and keratinocytes undergoing aging in vitro. RMHS given to human cells ...

  1. A gene expression programme induced by bovine colostrum whey promotes growth and wound-healing processes in intestinal epithelial cells

    OpenAIRE

    Blais, M.; Pouliot, Y.; Gauthier, S; Boutin, Y.; Lessard, M.

    2014-01-01

    Bovine colostrum is well known for its beneficial properties on health and development. It contains a wide variety of bioactive ingredients that are known to promote a number of cellular processes. Therefore the use of colostrum whey as a feed additive to promote intestinal health has been proposed, yet little is known about mechanisms implicated in its beneficial properties on intestinal epithelial cells. In the present paper, casein were removed from bovine colostrum and the remaining liqui...

  2. The Advantages of Traditional Chumash Healing

    OpenAIRE

    Cecilia Garcia; Adams, James D.

    2005-01-01

    Chumash healing has been practiced in California for ∼13 000 years. Chumash healers treat their patients with prayer, laughter, dreaming, phytotherapy, aromatherapy, healing ceremonies and other techniques. Healing involves first healing the spirit, then healing the body. Chumash people still maintain their unique identity. Chumash Healers still practice the ancient healing arts in California. This lecture is a brief introduction to Chumash Healing.

  3. Biophysical regulation of Chlamydia pneumoniae-infected monocyte recruitment to atherosclerotic foci

    Science.gov (United States)

    Evani, Shankar J.; Ramasubramanian, Anand K.

    2016-01-01

    Chlamydia pneumoniae infection is implicated in atherosclerosis although the contributory mechanisms are poorly understood. We hypothesize that C. pneumoniae infection favors the recruitment of monocytes to atherosclerotic foci by altering monocyte biophysics. Primary, fresh human monocytes were infected with C. pneumoniae for 8 h, and the interactions between monocytes and E-selectin or aortic endothelium under flow were characterized by video microscopy and image analysis. The distribution of membrane lipid rafts and adhesion receptors were analyzed by imaging flow cytometry. Infected cells rolled on E-selectin and endothelial surfaces, and this rolling was slower, steady and uniform compared to uninfected cells. Infection decreases cholesterol levels, increases membrane fluidity, disrupts lipid rafts, and redistributes CD44, which is the primary mediator of rolling interactions. Together, these changes translate to higher firm adhesion of infected monocytes on endothelium, which is enhanced in the presence of LDL. Uninfected monocytes treated with LDL or left untreated were used as baseline control. Our results demonstrate that the membrane biophysical changes due to infection and hyperlipidemia are one of the key mechanisms by which C. pneumoniae can exacerbate atherosclerotic pathology. These findings provide a framework to characterize the role of ‘infectious burden’ in the development and progression of atherosclerosis.

  4. Advances in combining gene therapy with cell and tissue engineering-based approaches to enhance healing of the meniscus.

    Science.gov (United States)

    Cucchiarini, M; McNulty, A L; Mauck, R L; Setton, L A; Guilak, F; Madry, H

    2016-08-01

    Meniscal lesions are common problems in orthopaedic surgery and sports medicine, and injury or loss of the meniscus accelerates the onset of knee osteoarthritis (OA). Despite a variety of therapeutic options in the clinics, there is a critical need for improved treatments to enhance meniscal repair. In this regard, combining gene-, cell-, and tissue engineering-based approaches is an attractive strategy to generate novel, effective therapies to treat meniscal lesions. In the present work, we provide an overview of the tools currently available to improve meniscal repair and discuss the progress and remaining challenges for potential future translation in patients. PMID:27063441

  5. Increased metabolite levels of glycolysis and pentose phosphate pathway in rabbit atherosclerotic arteries and hypoxic macrophage.

    Directory of Open Access Journals (Sweden)

    Atsushi Yamashita

    Full Text Available AIMS: Inflammation and possibly hypoxia largely affect glucose utilization in atherosclerotic arteries, which could alter many metabolic systems. However, metabolic changes in atherosclerotic plaques remain unknown. The present study aims to identify changes in metabolic systems relative to glucose uptake and hypoxia in rabbit atherosclerotic arteries and cultured macrophages. METHODS: Macrophage-rich or smooth muscle cell (SMC-rich neointima was created by balloon injury in the iliac-femoral arteries of rabbits fed with a 0.5% cholesterol diet or a conventional diet. THP-1 macrophages stimulated with lipopolysaccharides (LPS and interferon-γ (INFγ were cultured under normoxic and hypoxic conditions. We evaluated comprehensive arterial and macrophage metabolism by performing metabolomic analyses using capillary electrophoresis-time of flight mass spectrometry. We evaluated glucose uptake and its relationship to vascular hypoxia using (18F-fluorodeoxyglucose ((18F-FDG and pimonidazole, a marker of hypoxia. RESULTS: The levels of many metabolites increased in the iliac-femoral arteries with macrophage-rich neointima, compared with those that were not injured and those with SMC-rich neointima (glycolysis, 4 of 9; pentose phosphate pathway, 4 of 6; tricarboxylic acid cycle, 4 of 6; nucleotides, 10 of 20. The uptake of (18F-FDG in arterial walls measured by autoradiography positively correlated with macrophage- and pimonidazole-immunopositive areas (r = 0.76, and r = 0.59 respectively; n = 69 for both; p<0.0001. Pimonidazole immunoreactivity was closely localized with the nuclear translocation of hypoxia inducible factor-1α and hexokinase II expression in macrophage-rich neointima. The levels of glycolytic (8 of 8 and pentose phosphate pathway (4 of 6 metabolites increased in LPS and INFγ stimulated macrophages under hypoxic but not normoxic condition. Plasminogen activator inhibitor-1 protein levels in the supernatant were closely

  6. Endothelial lipase is highly expressed in macrophages in advanced human atherosclerotic lesions

    DEFF Research Database (Denmark)

    Bartels, Emil D; Nielsen, John E; Lindegaard, Marie Louise Skakkebæk;

    2007-01-01

    RNA expression increased markedly when either type of monocytes was differentiated into macrophages. Upon further differentiation into foam cells EL mRNA decreased whereas protein levels remained high compared to monocytes. In conclusion, macrophages in advanced human atherosclerotic lesions display high levels......, there was a positive association between the expression of EL mRNA and CD68 mRNA in plaques from 26 patients. The impact of differentiation from monocytes into macrophages, and subsequently foam cells (by incubation with acetylated LDL) on expression was studied using THP-1 monocytes and primary human monocytes. EL m...... of EL expression, and the level of EL expression varies greatly during transformation of blood monocytes into foam cells....

  7. Delivery of negatively charged liposomes into the atherosclerotic plaque of apolipoprotein E-deficient mouse aortic tissue.

    Science.gov (United States)

    Zhaorigetu, Siqin; Rodriguez-Aguayo, Cristian; Sood, Anil K; Lopez-Berestein, Gabriel; Walton, Brian L

    2014-09-01

    Liposomes have been used to diagnose and treat cancer and, to a lesser extent, cardiovascular disease. We previously showed the uptake of anionic liposomes into the atheromas of Watanabe heritable hyperlipidemic rabbits within lipid pools. However, the cellular distribution of anionic liposomes in atherosclerotic plaque remains undescribed. In addition, how anionic liposomes are absorbed into atherosclerotic plaque is unclear. We investigated the uptake and distribution of anionic liposomes in atherosclerotic plaque in aortic tissues from apolipoprotein E-deficient (ApoE(-/-)) mice. To facilitate the tracking of liposomes, we used liposomes containing fluorescently labeled non-silencing small interfering RNA. Confocal microscopy analysis showed the uptake of anionic liposomes into atherosclerotic plaque and colocalization with macrophages. Transmission electron microscopy analysis revealed anionic liposomal accumulation in macrophages. To investigate how anionic liposomes cross the local endothelial barrier, we examined the role of clathrin-mediated endocytosis in human coronary artery endothelial cells (HCAECs) treated with or without the inflammatory cytokine tumor necrosis factor (TNF)-α. Pretreatment with amantadine, an inhibitor of clathrin-mediated endocytosis, significantly decreased liposomal uptake in HCAECs treated with or without TNF-α by 77% and 46%, respectively. Immunoblot analysis showed that endogenous clathrin expression was significantly increased in HCAECs stimulated with TNF-α but was inhibited by amantadine. These studies indicated that clathrin-mediated endocytosis is partly responsible for the uptake of liposomes by endothelial cells. Our results suggest that anionic liposomes target macrophage-rich areas of vulnerable plaque in ApoE(-)(/)(-) mice; this finding may lead to the development of novel diagnostic and therapeutic strategies for treating vulnerable plaque in humans.

  8. Cellular events and biomarkers of wound healing

    Directory of Open Access Journals (Sweden)

    Shah Jumaat Mohd. Yussof

    2012-01-01

    Full Text Available Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth factors initiate fibroblast and keratinocyte proliferation. Inflammation is followed by the proliferation of fibroblasts, which lay down the extracellular matrix. Simultaneously, various white cells and other connective tissue cells release both the matrix metalloproteinases (MMPs and the tissue inhibitors of these metalloproteinases (TIMPs. MMPs remove damaged structural proteins such as collagen, while the fibroblasts lay down fresh extracellular matrix proteins. Fluid collected from acute, healing wounds contains growth factors, and stimulates fibroblast proliferation, but fluid collected from chronic, nonhealing wounds does not. Fibroblasts from chronic wounds do not respond to chronic wound fluid, probably because the fibroblasts of these wounds have lost the receptors that respond to cytokines and growth factors. Nonhealing wounds contain high levels of IL1, IL6, and MMPs, and an abnormally high MMP/TIMP ratio. Clinical examination of wounds inconsistently predicts which wounds will heal when procedures like secondary closure are planned. Surgeons therefore hope that these chemicals can be used as biomarkers of wounds which have impaired ability to heal. There is also evidence that the application of growth factors like PDGF will help the healing of chronic, nonhealing wounds.

  9. General concept of wound healing, revisited

    Directory of Open Access Journals (Sweden)

    Theddeus O.H. Prasetyono

    2009-09-01

    Full Text Available Wound healing is a transition of processes which is also recognized as one of the most complex processes in human physiology. Complex series of reactions and interactions among cells and mediators take place in the healing process of wound involving cellular and molecular events. The inflammatory phase is naturally intended to remove devitalized tissue and prevent invasive infection. The proliferative phase is characterized by the formation of granulation tissue within the wound bed, composed of new capillary network, fibroblast, and macrophages in a loose arrangement of supporting structure. This second phase lasts from day 8 to 21 after the injury is also the phase for epithelialisation. The natural period of proliferative phase is a reflection for us in treating wound to reach the goal which ultimately defines as closed wound. The final maturation phase is also characterized by the balancing between deposition of collagen and its degradation. There are at least three prerequisites which are ideal local conditions for the nature of wound to go on a normal process of healing i.e. 1 all tissue involved in the wound and surrounding should be vital, 2 no foreign bodies in the wound, and 3 free from excessive contamination/infection. The author formulated a step ladder of thinking in regards of healing intentions covering all acute and chronic wounds. Regarding the “hierarchy” of healing intention, the fi rst and ideal choice to heal wounds is by primary intention followed by tertiary intention and lastly the secondary intention. (Med J Indones 2009;18:206-14Key words: inflammatory mediator, epithelialisation, growth factor, wound healing

  10. Bee Venom Accelerates Wound Healing in Diabetic Mice by Suppressing Activating Transcription Factor-3 (ATF-3) and Inducible Nitric Oxide Synthase (iNOS)-Mediated Oxidative Stress and Recruiting Bone Marrow-Derived Endothelial Progenitor Cells.

    Science.gov (United States)

    Badr, Gamal; Hozzein, Wael N; Badr, Badr M; Al Ghamdi, Ahmad; Saad Eldien, Heba M; Garraud, Olivier

    2016-10-01

    Multiple mechanisms contribute to impaired diabetic wound healing including impaired neovascularization and deficient endothelial progenitor cell (EPC) recruitment. Bee venom (BV) has been used as an anti-inflammatory agent for the treatment of several diseases. Nevertheless, the effect of BV on the healing of diabetic wounds has not been studied. Therefore, in this study, we investigated the impact of BV on diabetic wound closure in a type I diabetic mouse model. Three experimental groups were used: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated with BV. We found that the diabetic mice exhibited delayed wound closure characterized by a significant decrease in collagen production and prolonged elevation of inflammatory cytokines levels in wounded tissue compared to control non-diabetic mice. Additionally, wounded tissue in diabetic mice revealed aberrantly up-regulated expression of ATF-3 and iNOS followed by a marked elevation in free radical levels. Impaired diabetic wound healing was also characterized by a significant elevation in caspase-3, -8, and -9 activity and a marked reduction in the expression of TGF-β and VEGF, which led to decreased neovascularization and angiogenesis of the injured tissue by impairing EPC mobilization. Interestingly, BV treatment significantly enhanced wound closure in diabetic mice by increasing collagen production and restoring the levels of inflammatory cytokines, free radical, TGF-β, and VEGF. Most importantly, BV-treated diabetic mice exhibited mobilized long-lived EPCs by inhibiting caspase activity in the wounded tissue. Our findings reveal the molecular mechanisms underlying improved diabetic wound healing and closure following BV treatment. J. Cell. Physiol. 231: 2159-2171, 2016. © 2016 Wiley Periodicals, Inc. PMID:26825453

  11. Congenital self healing Langerhans cell histiocytosis%先天性自愈性朗格汉斯组织细胞增生症

    Institute of Scientific and Technical Information of China (English)

    皮肖冰; 王晓霞

    2011-01-01

    报告1例先天性自愈性朗格汉斯组织细胞增生症.患儿男,2个月.出生时即有全身多发性皮肤结节,皮肤科检查:左耳后、左面部、胸部、背部、左下肢、右示指共6处鲜红色结节,中央形成火山口状溃疡,组织病理示结节由梭形细胞构成,部分细胞胞质丰富,嗜酸性,可见多角、多核瘤巨细胞,间质纤维丰富,局部瘤细胞增生活跃.免疫组化:CD1a(+),S-100蛋白(±),CD68(-),切除5处皮肤结节,右示指处结节未切除,在10个月内自行消失,结合患儿临床症状及随访结果诊断为先天性自愈性朗格汉斯组织细胞增生症.%A 2-month-old male was born with 6 nodules on the left posterior auris, left face, the breast, the back ,the left leg and right index finger.Physical examination showed red nodules with central crateriform ulceration.Histopathological examination revealed spindle cells, some were mononuclear histiocytes with abundant eosinophilic or foamy cytoplasm.Polynucleart tumor giant cells and abundant interstitial substance were seen in the dermis.These mononuclear histiocytoid cells were stained positive for S-100 protein and CD1a negative for CD 68.5 nudules were excised, and spontaneous resolving occurred to the remaining nodule in the right index finger within 10 months.The diagnosis of congenital self-healing Langerhans cell histiocytosis was finally established.

  12. The external microenvironment of healing skin wounds

    DEFF Research Database (Denmark)

    Kruse, Carla R; Nuutila, Kristo; Lee, Cameron Cy;

    2015-01-01

    The skin wound microenvironment can be divided into two main components that influence healing: the external wound microenvironment, which is outside the wound surface; and the internal wound microenvironment, underneath the surface, to which the cells within the wound are exposed. Treatment...

  13. Healing the nations

    Directory of Open Access Journals (Sweden)

    Karl Dortzbach

    2004-10-01

    Full Text Available This article gives the motivations, methodology and some results of a study done in Christian healing interventions in African contexts of� stress and violence. Healing in community has been viewed through the prism of �shalom�. Shalom occurs when people who are in a� right� relationship with God� and� each other enjoy and share together the resources of the earth� in ways� that� show Christ� is Lord of all creation. Charts are given showing� the various kinds of community needs, ways to intervene, and some indications of ways to evaluate the interventions.

  14. The science of ultrasound therapy for fracture healing

    Directory of Open Access Journals (Sweden)

    Della Rocca Gregory

    2009-01-01

    Full Text Available Fracture healing involves a complex interplay of cellular processes, culminating in bridging of a fracture gap with bone. Fracture healing can be compromised by numerous exogenous and endogenous patient factors, and intense research is currently going on to identify modalities that can increase the likelihood of successful healing. Low-intensity pulsed ultrasound (LIPUS has been proposed as a modality that may have a benefit for increasing reliable fracture healing as well as perhaps increasing the rate of fracture healing. We conducted a review to establish basic scince evidence of therapeutic role of lipus in fracture healing. An electronic search without language restrictions was accomplished of three databases (PubMed, Embase, Cinahl for ultrasound-related research in osteocyte and chondrocyte cell culture and in animal fracture models, published from inception of the databases through December, 2008. Studies deemed to be most relevant were included in this review. Multiple in vitro and animal in vivo studies were identified. An extensive body of literature exists which delineates the mechanism of action for ultrasound on cellular and tissue signaling systems that may be related to fracture healing. Research on LIPUS in animal fracture models has demonstrated promising results for acceleration of fracture healing and for promotion of fracture healing in compromised tissue beds. A large body of cellular and animal research exists which reveals that LIPUS may be beneficial for accelerating normal fracture healing or for promoting fracture healing in compromised tissue beds. Further investigation of the effects of LIPUS in human fracture healing is warranted for this promising new therapy.

  15. The science of ultrasound therapy for fracture healing.

    Science.gov (United States)

    Della Rocca, Gregory J

    2009-01-01

    Fracture healing involves a complex interplay of cellular processes, culminating in bridging of a fracture gap with bone. Fracture healing can be compromised by numerous exogenous and endogenous patient factors, and intense research is currently going on to identify modalities that can increase the likelihood of successful healing. Low-intensity pulsed ultrasound (LIPUS) has been proposed as a modality that may have a benefit for increasing reliable fracture healing as well as perhaps increasing the rate of fracture healing. We conducted a review to establish basic scince evidence of therapeutic role of lipus in fracture healing. An electronic search without language restrictions was accomplished of three databases (PubMed, Embase, Cinahl) for ultrasound-related research in osteocyte and chondrocyte cell culture and in animal fracture models, published from inception of the databases through December, 2008. Studies deemed to be most relevant were included in this review. Multiple in vitro and animal in vivo studies were identified. An extensive body of literature exists which delineates the mechanism of action for ultrasound on cellular and tissue signaling systems that may be related to fracture healing. Research on LIPUS in animal fracture models has demonstrated promising results for acceleration of fracture healing and for promotion of fracture healing in compromised tissue beds. A large body of cellular and animal research exists which reveals that LIPUS may be beneficial for accelerating normal fracture healing or for promoting fracture healing in compromised tissue beds. Further investigation of the effects of LIPUS in human fracture healing is warranted for this promising new therapy.

  16. Identification and functional analysis of healing regulators in Drosophila.

    Science.gov (United States)

    Álvarez-Fernández, Carmen; Tamirisa, Srividya; Prada, Federico; Chernomoretz, Ariel; Podhajcer, Osvaldo; Blanco, Enrique; Martín-Blanco, Enrique

    2015-01-01

    Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the overall steps in wound healing, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process. However, they do allow the less understood aspects of the healing response to be explored, e.g., which signal(s) are responsible for initiating tissue remodeling? How is sealing of the epithelia achieved? Or, what inhibitory cues cancel the healing machinery upon completion? Answering these and other questions first requires the identification and functional analysis of wound specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method that is healing-permissive and that allows live imaging and biochemical analysis of cultured imaginal discs. We performed comparative genome-wide profiling between Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. Sets of potential wound-specific genes were subsequently identified. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in healing assays. This non-saturated analysis defines a relevant set of genes whose changes in expression level are functionally significant for proper tissue repair. Amongst these we identified the TCP1 chaperonin complex as a key regulator of the actin cytoskeleton essential for the wound healing response. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound healing response.

  17. Identification and functional analysis of healing regulators in Drosophila.

    Directory of Open Access Journals (Sweden)

    Carmen Álvarez-Fernández

    Full Text Available Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the overall steps in wound healing, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process. However, they do allow the less understood aspects of the healing response to be explored, e.g., which signal(s are responsible for initiating tissue remodeling? How is sealing of the epithelia achieved? Or, what inhibitory cues cancel the healing machinery upon completion? Answering these and other questions first requires the identification and functional analysis of wound specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method that is healing-permissive and that allows live imaging and biochemical analysis of cultured imaginal discs. We performed comparative genome-wide profiling between Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. Sets of potential wound-specific genes were subsequently identified. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in healing assays. This non-saturated analysis defines a relevant set of genes whose changes in expression level are functionally significant for proper tissue repair. Amongst these we identified the TCP1 chaperonin complex as a key regulator of the actin cytoskeleton essential for the wound healing response. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound healing response.

  18. Angiogenesis and vasculogenesis: inducing the growth of new blood vessels and wound healing by stimulation of bone marrow-derived progenitor cell mobilization and homing.

    Science.gov (United States)

    Velazquez, Omaida C

    2007-06-01

    During embryonic development, the vasculature is among the first organs to form and is in charge of maintaining metabolic homeostasis by supplying oxygen and nutrients and removing waste products. As one would expect, blood vessels are critical not only for organ growth in the embryo but also for repair of wounded tissue in the adult. An imbalance in angiogenesis (a time-honored term that globally refers to the growth of new blood vessels) contributes to the pathogenesis of numerous malignant, inflammatory, ischemic, infectious, immune, and wound-healing disorders. This review focuses on the central role of the growth of new blood vessels in ischemic and diabetic wound healing and defines the most current nomenclature that describes the neovascularization process in wounds. There are now two well-defined, distinct, yet interrelated processes for the formation of postnatal new blood vessels, angiogenesis, and vasculogenesis. Reviewed are recent new data on vasculogenesis that promise to advance the field of wound healing.

  19. Serum adiponectin level in hypertensive patients and its association with atherosclerotic risk factors

    Directory of Open Access Journals (Sweden)

    Bülent Uygungelen

    2013-06-01

    Full Text Available Aim. Hypertension is one of the major risk factors for atherosclerosis. Adiponectin is mainly synthesized by white adipose tissue; it is known to have anti-atherogenic and anti-inflammatory effects on endothelial cells and macrophages. Methods. A total of 80 individuals including 48 hypertensive and 32 normotensive individuals were included in the study. Groups were separated as obese and non-obese. Results. It was found out that the patient group had statistically higher systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, triglyceride, low density lipoprotein, high sensitive C reactive protein and microalbuminuria values than the control group while high density lipoprotein values were significantly lower (p<0.05. When adiponectin levels of the groups were compared, the patient group had an adiponectin level of 8.66±2.75 µg/mL and the control group had an adiponectin level of 15.01±3.99 µg/mL. There was a statistically significant difference between two groups (p<0.05. There was a negative correlation between adiponectin level and atherosclerotic risk factors. Conclusion. Adiponectin level was lower in hypertensive group when compared to the control group; there was also a significant association between adiponectin and atherosclerotic risk factors. A low adiponectin level constitutes an important risk for development of atherosclerosis.

  20. The heme-heme oxygenase system in wound healing; implications for scar formation.

    NARCIS (Netherlands)

    Wagener, F.A.D.T.G.; Scharstuhl, A.; Tyrrell, R.M.; Hoff, J.W. von den; Jozkowicz, A.; Dulak, J.; Russel, F.G.M.; Kuijpers-Jagtman, A.M.

    2010-01-01

    Wound healing is an intricate process requiring the concerted action of keratinocytes, fibroblasts, endothelial cells, and macrophages. Here, we review the literature on normal wound healing and the pathological forms of wound healing, such as hypertrophic or excessive scar formation, with special e

  1. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    International Nuclear Information System (INIS)

    Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstable or vulnerable to rupture. The presence of inflammation in the atherosclerotic plaque has been considered as one of the initial events which convert a stable plaque into an unstable and vulnerable plaque. This paper systemically reviews the noninvasive and invasive imaging modalities that are currently available to detect this inflammatory process, at least in the intermediate stages, and discusses the ongoing studies that will help us to better understand and identify it at the molecular level

  2. In silico analyses of metagenomes from human atherosclerotic plaque samples

    DEFF Research Database (Denmark)

    Mitra, Suparna; Drautz-Moses, Daniela I; Alhede, Morten;

    2015-01-01

    BACKGROUND: Through several observational and mechanistic studies, microbial infection is known to promote cardiovascular disease. Direct infection of the vessel wall, along with the cardiovascular risk factors, is hypothesized to play a key role in the atherogenesis by promoting an inflammatory...... response leading to endothelial dysfunction and generating a proatherogenic and prothrombotic environment ultimately leading to clinical manifestations of cardiovascular disease, e.g., acute myocardial infarction or stroke. There are many reports of microbial DNA isolation and even a few studies of viable...... a challenge. RESULTS: To investigate microbiome diversity within human atherosclerotic tissue samples, we employed high-throughput metagenomic analysis on: (1) atherosclerotic plaques obtained from a group of patients who underwent endarterectomy due to recent transient cerebral ischemia or stroke. (2...

  3. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    Directory of Open Access Journals (Sweden)

    Sunny Goel

    2015-01-01

    Full Text Available Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstable or vulnerable to rupture. The presence of inflammation in the atherosclerotic plaque has been considered as one of the initial events which convert a stable plaque into an unstable and vulnerable plaque. This paper systemically reviews the noninvasive and invasive imaging modalities that are currently available to detect this inflammatory process, at least in the intermediate stages, and discusses the ongoing studies that will help us to better understand and identify it at the molecular level.

  4. Augmentation of tendon-to-bone healing.

    Science.gov (United States)

    Atesok, Kivanc; Fu, Freddie H; Wolf, Megan R; Ochi, Mitsuo; Jazrawi, Laith M; Doral, M Nedim; Lubowitz, James H; Rodeo, Scott A

    2014-03-19

    Tendon-to-bone healing is vital to the ultimate success of the various surgical procedures performed to repair injured tendons. Achieving tendon-to-bone healing that is functionally and biologically similar to native anatomy can be challenging because of the limited regeneration capacity of the tendon-bone interface. Orthopaedic basic-science research strategies aiming to augment tendon-to-bone healing include the use of osteoinductive growth factors, platelet-rich plasma, gene therapy, enveloping the grafts with periosteum, osteoconductive materials, cell-based therapies, biodegradable scaffolds, and biomimetic patches. Low-intensity pulsed ultrasound and extracorporeal shockwave treatment may affect tendon-to-bone healing by means of mechanical forces that stimulate biological cascades at the insertion site. Application of various loading methods and immobilization times influence the stress forces acting on the recently repaired tendon-to-bone attachment, which eventually may change the biological dynamics of the interface. Other approaches, such as the use of coated sutures and interference screws, aim to deliver biological factors while achieving mechanical stability by means of various fixators. Controlled Level-I human trials are required to confirm the promising results from in vitro or animal research studies elucidating the mechanisms underlying tendon-to-bone healing and to translate these results into clinical practice. PMID:24647509

  5. Gene expression and 18FDG uptake in atherosclerotic carotid plaques

    DEFF Research Database (Denmark)

    Pedersen, Sune Folke; Græbe, Martin; Hag, Anne Mette Fisker;

    2010-01-01

    ) and an additional ipsilateral internal carotid artery stenosis of greater than 60% were recruited. FDG uptake in the carotids was determined by PET/computed tomography and expressed as mean and maximal standardized uptake values (SUVmean and SUVmax). The atherosclerotic plaques were subsequently recovered...... as SUVmax (R=0.30, Puptake. We suggest that FDG uptake is a composite indicator of macrophage load, overall inflammatory activity and collagenolytic plaque...

  6. Severe Brown Fat Lipoatrophy Aggravates Atherosclerotic Process in Male Mice.

    Science.gov (United States)

    Gómez-Hernández, Almudena; Beneit, Nuria; Escribano, Óscar; Díaz-Castroverde, Sabela; García-Gómez, Gema; Fernández, Silvia; Benito, Manuel

    2016-09-01

    Obesity is one of the major risk factors for the development of cardiovascular diseases and is characterized by abnormal accumulation of adipose tissue, including perivascular adipose tissue (PVAT). However, brown adipose tissue (BAT) activation reduces visceral adiposity. To demonstrate that severe brown fat lipoatrophy might accelerate atherosclerotic process, we generated a new mouse model without insulin receptor (IR) in BAT and without apolipoprotein (Apo)E (BAT-specific IR knockout [BATIRKO];ApoE(-/-) mice) and assessed vascular and metabolic alterations associated to obesity. In addition, we analyzed the contribution of the adipose organ to vascular inflammation. Brown fat lipoatrophy induces visceral adiposity, mainly in gonadal depot (gonadal white adipose tissue [gWAT]), severe glucose intolerance, high postprandial glucose levels, and a severe defect in acute insulin secretion. BATIRKO;ApoE(-/-) mice showed greater hypertriglyceridemia than the obtained in ApoE(-/-) and hypercholesterolemia similar to ApoE(-/-) mice. BATIRKO;ApoE(-/-) mice, in addition to primary insulin resistance in BAT, also showed a significant decrease in insulin signaling in liver, gWAT, heart, aorta artery, and thoracic PVAT. More importantly, our results suggest that severe brown fat lipoatrophy aggravates the atherosclerotic process, characterized by a significant increase of lipid depots, atherosclerotic coverage, lesion size and complexity, increased macrophage infiltration, and proinflammatory markers expression. Finally, an increase of TNF-α and leptin as well as a decrease of adiponectin by BAT, gWAT, and thoracic PVAT might also be responsible of vascular damage. Our results suggest that severe brown lipoatrophy aggravates atherosclerotic process. Thus, BAT activation might protect against obesity and its associated metabolic alterations. PMID:27414981

  7. Self-healing supramolecular nanocomposites

    OpenAIRE

    Liu, Z.

    2015-01-01

    The aim of this thesis is to execute a bottom-up design of the intrinsically self-healing nanocomposites. We briefly introduced the self-healing materials in chapter 1, covering classification and basic self-healing mechanism. In chapter 2, we have synthesized polyborosiloxane (PBS) according to the last century recipe as the self-healing supramolecular matrix. Additionally, we provided the long existing recipe with exclusive supplementary details, such as reaction kinetics, structural refine...

  8. High speed intravascular photoacoustic imaging of atherosclerotic arteries (Conference Presentation)

    Science.gov (United States)

    Piao, Zhonglie; Ma, Teng; Qu, Yueqiao; Li, Jiawen; Yu, Mingyue; He, Youmin; Shung, K. Kirk; Zhou, Qifa; Kim, Chang-Seok; Chen, Zhongping

    2016-02-01

    Cardiovascular disease is the leading cause of death in the industrialized nations. Accurate quantification of both the morphology and composition of lipid-rich vulnerable atherosclerotic plaque are essential for early detection and optimal treatment in clinics. In previous works, intravascular photoacoustic (IVPA) imaging for detection of lipid-rich plaque within coronary artery walls has been demonstrated in ex vivo, but the imaging speed is still limited. In order to increase the imaging speed, a high repetition rate laser is needed. In this work, we present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A miniature catheter with 1.0 mm outer diameter was designed with a 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. The fiber was polished at 38 degree and enclosed in a glass capillary for total internal reflection. An optical/electrical rotary junction and pull-back mechanism was applied for rotating and linearly scanning the catheter to obtain three-dimensional imaging. Atherosclerotic rabbit abdominal aorta was imaged as two frame/second at 1725 nm. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo. The results demonstrated that the developed IVPA/US imaging system is capable for high speed intravascular imaging for plaque detection.

  9. Healing Invisible Wounds

    Science.gov (United States)

    Adams, Erica J.

    2010-01-01

    As many as 9 in 10 justice-involved youth are affected by traumatic childhood experiences. According to "Healing Invisible Wounds: Why Investing in Trauma-Informed Care for Children Makes Sense," between 75 and 93 percent of youth currently incarcerated in the justice system have had at least one traumatic experience, including sexual abuse, war,…

  10. The arts as healing.

    Science.gov (United States)

    Kivnick, H Q; Erikson, J M

    1983-10-01

    The relationship between artistic involvement and individual mental health is considered, and the concept of "healing" is differentiated from that of "therapy." Seven properties of art experience are identified which, when developed, have contributed to patients' recovery from mental illness. Implications of these properties for clinical programs, and the related value of art experience for non-patients, are discussed. PMID:6638153

  11. Phytochemicals in Wound Healing

    OpenAIRE

    Thangapazham, Rajesh L.; Sharad, Shashwat; Radha K. Maheshwari

    2016-01-01

    Significance: Traditional therapies, including the use of dietary components for wound healing and skin regeneration, are very common in Asian countries such as China and India. The increasing evidence of health-protective benefits of phytochemicals, components derived from plants is generating a lot of interest, warranting further scientific evaluation and mechanistic studies.

  12. Endothelial lipase is highly expressed in macrophages in advanced human atherosclerotic lesions

    DEFF Research Database (Denmark)

    Bartels, Emil D; Nielsen, John E; Lindegaard, Marie Louise Skakkebæk;

    2007-01-01

    , there was a positive association between the expression of EL mRNA and CD68 mRNA in plaques from 26 patients. The impact of differentiation from monocytes into macrophages, and subsequently foam cells (by incubation with acetylated LDL) on expression was studied using THP-1 monocytes and primary human monocytes. EL m...... on sections of carotid endarterectomy specimens from patients with symptomatic cerebrovascular disease. In each of eight patients, EL mRNA and/or protein were seen in areas between the necrotic core and the fibrotic cap where they colocalized with LPL and macrophage-specific CD68. Moreover......RNA expression increased markedly when either type of monocytes was differentiated into macrophages. Upon further differentiation into foam cells EL mRNA decreased whereas protein levels remained high compared to monocytes. In conclusion, macrophages in advanced human atherosclerotic lesions display high levels...

  13. Diffuse Dermal Angiomatosis: A Clue to the Diagnosis of Atherosclerotic Vascular Disease

    Directory of Open Access Journals (Sweden)

    Tueboon Sriphojanart

    2015-05-01

    Full Text Available Diffuse dermal angiomatosis (DDA is a benign, acquired, reactive vascular proliferation. DDA is clinically characterized by painful purpuric plaque with central ulceration. The histopathologic hallmark is diffuse proliferation of endothelial cells that are arranged interstitially between collagen bundles of the reticular dermis. DDA has been reported in association with peripheral atherosclerotic disease, arteriovenous fistula and heavy smoking. We report the case of a 49-year-old Asian male with DDA who presented with a painful stellate-shaped purpuric patch on the right thigh. Histopathologic examination showed proliferation of CD34-positive spindle cells in the dermis. Our patient underwent vascular bypass surgery along with tight control of cardiovascular risk factors, which yielded successful results.

  14. Predicting Young's modulus of glass/ceramic sealant for solid oxide fuel cell considering the combined effects of aging, micro-voids and self-healing

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wenning; Sun, Xin; Khaleel, Mohammad A. [Pacific Northwest National Laboratory, P.O. Box 999, Richland, WA 99354 (United States)

    2008-12-01

    We study the temperature dependent Young's modulus for the glass/ceramic seal material used in solid oxide fuel cells (SOFCs). With longer heat treatment or aging time during operation, further devitrification may reduce the residual glass content in the seal material while boosting the ceramic crystalline content. In the meantime, micro-voids induced by the cooling process from the high operating temperature to room temperature can potentially degrade the mechanical properties of the glass/ceramic sealant. Upon reheating to the SOFC operating temperature, possible self-healing phenomenon may occur in the glass/ceramic sealant which can potentially restore some of its mechanical properties. A phenomenological model is developed to model the temperature dependent Young's modulus of glass/ceramic seal considering the combined effects of aging, micro-voids, and possible self-healing. An aging time-dependent crystalline content model is first developed to describe the increase of the crystalline content due to the continuing devitrification under high operating temperature. A continuum damage mechanics (CDM) model is then adapted to model the effects of both cooling induced micro-voids and reheating induced self-healing. This model is applied to model the glass-ceramic G18, a candidate SOFC seal material previously developed at PNNL. Experimentally determined temperature-dependent Young's modulus is used to validate the model predictions. (author)

  15. The effects of caffeine on wound healing.

    Science.gov (United States)

    Ojeh, Nkemcho; Stojadinovic, Olivera; Pastar, Irena; Sawaya, Andrew; Yin, Natalie; Tomic-Canic, Marjana

    2016-10-01

    The purine alkaloid caffeine is a major component of many beverages such as coffee and tea. Caffeine and its metabolites theobromine and xanthine have been shown to have antioxidant properties. Caffeine can also act as adenosine-receptor antagonist. Although it has been shown that adenosine and antioxidants promote wound healing, the effect of caffeine on wound healing is currently unknown. To investigate the effects of caffeine on processes involved in epithelialisation, we used primary human keratinocytes, HaCaT cell line and ex vivo model of human skin. First, we tested the effects of caffeine on cell proliferation, differentiation, adhesion and migration, processes essential for normal wound epithelialisation and closure. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) proliferation assay to test the effects of seven different caffeine doses ranging from 0·1 to 5 mM. We found that caffeine restricted cell proliferation of keratinocytes in a dose-dependent manner. Furthermore, scratch wound assays performed on keratinocyte monolayers indicated dose-dependent delays in cell migration. Interestingly, adhesion and differentiation remained unaffected in monolayer cultures treated with various doses of caffeine. Using a human ex vivo wound healing model, we tested topical application of caffeine and found that it impedes epithelialisation, confirming in vitro data. We conclude that caffeine, which is known to have antioxidant properties, impedes keratinocyte proliferation and migration, suggesting that it may have an inhibitory effect on wound healing and epithelialisation. Therefore, our findings are more in support of a role for caffeine as adenosine-receptor antagonist that would negate the effect of adenosine in promoting wound healing.

  16. Self-healing polymers

    Science.gov (United States)

    Klein, Daniel J. (Inventor)

    2011-01-01

    A three dimensional structure fabricated from a self-healing polymeric material, comprising poly(ester amides) obtained from ethylene glycol, azelaic acid and 1,1-aminoundecanoic acid, wherein polymeric material has a melt index above 2.5 g/10 min. as determined by ASTM D1238 at 190.degree. C. and 2.16kg, impact resistance and ductility sufficient to resist cracking and brittle fracture upon impact by a 9 mm bullet fired at a temperature of about 29.degree. C. at subsonic speed in a range from about 800 feet/sec to about 1000 feet/sec. It has been determined that the important factors necessary for self-healing behavior of polymers include sufficient impact strength, control of the degree of crystallinity, low melting point and the ability to instantly melt at impacted area.

  17. Links between atherosclerotic and periodontal disease.

    Science.gov (United States)

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-02-01

    Periodontal disease (PD) and cardiovascular disease (CVD) are highly prevalent in the modern community. Both pathologies are chronic inflammatory disorders, which are influenced by multiple risk factors. In part, these factors such as age, smoking, and diabetes overlap between PD and CVD. Epidemiological studies suggest that PD is strongly associated with increased CVD risk. Biochemical and physiological analyses involving in vitro experiments, animal models, and clinical studies provided evidence for the substantial impact of periodontal pathogens, their virulence factors, and bacterial endotoxins on all general pathogenic CVD mechanisms such as endothelial dysfunction, systemic inflammation, oxidative stress, foam cell formation, lipid accumulation, vascular remodeling, and atherothrombosis. Interventional studies showed moderate beneficial effects of PD treatment on reducing systemic inflammation and endothelial dysfunction. However, no interventional studies were performed to assess whether periodontal therapy can primarily prevent CVD. In summary, current data suggest for a strong contributory role of periodontal infection to CVD but cannot provide sufficient evidence for a role of PD as a cause for cardiovascular pathology. PMID:26777261

  18. Lipocalin (LCN 2 Mediates Pro-Atherosclerotic Processes and Is Elevated in Patients with Coronary Artery Disease.

    Directory of Open Access Journals (Sweden)

    Raghav Oberoi

    Full Text Available Lipocalin (LCN 2 is associated with multiple acute and chronic inflammatory diseases but the underlying molecular and cellular mechanisms remain unclear. Here, we investigated whether LCN2 is released from macrophages and contributes to pro-atherosclerotic processes and whether LCN2 plasma levels are associated with the severity of coronary artery disease progression in humans.In an autocrine-paracrine loop, tumor necrosis factor (TNF-α promoted the release of LCN2 from murine bone-marrow derived macrophages (BMDM and vice versa. Moreover, LCN2 stimulation of BMDM led to up-regulation of M1 macrophage markers. In addition, enhanced migration of monocytic J774A.1 cells towards LCN2 was observed. Furthermore, LCN2 increased the expression of the scavenger receptors Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1 as well as scavenger receptor class A-1 (SRA-1 and induced the conversion of macrophages to foam cells. In atherosclerotic lesions of low density lipoprotein receptor-deficient (ldlr-/- mice fed a high fat, high cholesterol diet, LCN2 was found to be co-localized with macrophages in the shoulder region of the atherosclerotic plaque. In addition, LCN2 plasma levels were significantly increased in plasma samples of these mice. Finally, LCN2 plasma levels correlated with the severity of coronary artery disease (CAD in patients as determined by coronary angiography.Here we demonstrated that LCN2 plays a pivotal role in processes involved in atherogenesis by promoting polarization and migration of monocytic cells and development of macrophages towards foam cells. Moreover, LCN2 may be used as a prognostic marker to determine the status of CAD progression.

  19. Gene expression of LOX-1, VCAM-1, and ICAM-1 in pre-atherosclerotic mice

    DEFF Research Database (Denmark)

    Fisker Hag, Anne Mette; Pedersen, Sune Folke; Kjaer, Andreas

    2008-01-01

    To identify markers of the earliest stage of atherosclerosis, endothelial dysfunction, we evaluated the gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in very young pre......-atherosclerotic mice. Furthermore, the plasma levels of the soluble VCAM-1 and ICAM-1 were compared to the gene expression profiles. Gene expressions of LOX-1 and VCAM-1 were up-regulated in young apoE(-/-) mice, and thus, it seems probable that these genes play a role in pre-atherosclerosis. Contrarily, the gene...... expression profile of ICAM-1 did not show any apparent differences between the groups, questioning the involvement of this molecule in the early development of atherosclerosis. Plasma levels of sVCAM-1 and sICAM-1 were similar in all mice and did not correlate with the vascular gene expression...

  20. {sup 18}F-FDG in distinction of atherosclerotic plaque: Innovation in PET/MRI technology

    Energy Technology Data Exchange (ETDEWEB)

    Benedetto, Raquel; Fonseca, Lea Mirian Barbosa da, E-mail: benedettoraquel@yahoo.com.b [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Carneiro, Michel Pontes; Junqueira, Flavia Albuquerque; Coutinho Junior, Antonio [Clinica de Diagnostico por Imagem (CDPI), Rio de Janeiro, RJ (Brazil); Ristow, Arno von [Centervasc, Rio de Janeiro, RJ (Brazil)

    2009-12-15

    The glucose analogue, {sup 18}F-FDG, can be used to image inflammatory cell activity non-invasively by PET. In the present study, we investigate the possibility of using {sup 18}F-FDG to characterize atherosclerotic plaques. A 77-year-old man with symptomatic carotid atherosclerosis was imaged using {sup 18}F-FDG-PET and co-registered MRI. A plaque with intense fibrotic and necrotic content was obtained. Due to the fact that the tissue showed up as inactive, according to the metabolic activity, it was not possible to observe {sup 18}F-FDG uptake. Our aim was to confirm that it could be clinically used to predict the inflammatory activity of the plaque. (author)

  1. Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression.

    Science.gov (United States)

    Woollard, Kevin J; Lumsden, Natalie G; Andrews, Karen L; Aprico, Andrea; Harris, Emma; Irvine, Jennifer C; Jefferis, Ann-maree; Fang, Lu; Kanellakis, Peter; Bobik, Alex; Chin-Dusting, Jaye P F

    2014-01-01

    Soluble P-selectin (sP-selectin), a biomarker of inflammatory related pathologies including cardiovascular and peripheral vascular diseases, also has pro-atherosclerotic effects including the ability to increase leukocyte recruitment and modulate thrombotic responses in vivo. The current study explores its role in progressing atherosclerotic plaque disease. Apoe-/- mice placed on a high fat diet (HFD) were given daily injections of recombinant dimeric murine P-selectin (22.5 µg/kg/day) for 8 or 16 weeks. Saline or sE-selectin injections were used as negative controls. In order to assess the role of sP-selectin on atherothrombosis an experimental plaque remodelling murine model, with sm22α-hDTR Apoe-/- mice on a HFD in conjunction with delivery of diphtheria toxin to induce targeted vascular smooth muscle apoptosis, was used. These mice were similarly given daily injections of sP-selectin for 8 or 16 weeks. While plaque mass and aortic lipid content did not change with sP-selectin treatment in Apoe-/- or SM22α-hDTR Apoe-/- mice on HFD, increased plasma MCP-1 and a higher plaque CD45 content in Apoe-/- HFD mice was observed. As well, a significant shift towards a more unstable plaque phenotype in the SM22α-hDTR Apoe-/- HFD mice, with increased macrophage accumulation and lower collagen content, leading to a lower plaque stability index, was observed. These results demonstrate that chronically raised sP-selectin favours progression of an unstable atherosclerotic plaque phenotype.

  2. The Advantages of Traditional Chumash Healing

    Directory of Open Access Journals (Sweden)

    James D. Adams

    2005-01-01

    Full Text Available Chumash healing has been practiced in California for ∼13 000 years. Chumash healers treat their patients with prayer, laughter, dreaming, phytotherapy, aromatherapy, healing ceremonies and other techniques. Healing involves first healing the spirit, then healing the body. Chumash people still maintain their unique identity. Chumash Healers still practice the ancient healing arts in California. This lecture is a brief introduction to Chumash Healing.

  3. In Vivo Study of Ligament-Bone Healing after Anterior Cruciate Ligament Reconstruction Using Autologous Tendons with Mesenchymal Stem Cells Affinity Peptide Conjugated Electrospun Nanofibrous Scaffold

    Directory of Open Access Journals (Sweden)

    Jingxian Zhu

    2013-01-01

    Full Text Available Electrospinning nanofibrous scaffold was commonly used in tissue regeneration recently. Nanofibers with specific topological characteristics were reported to be able to induce osteogenic differentiation of MSCs. In this in vivo study, autologous tendon grafts with lattice-like nanofibrous scaffold wrapping at two ends of autologous tendon were used to promote early stage of ligament-bone healing after rabbit ACL reconstruction. To utilize native MSCs from bone marrow, an MSCs specific affinity peptide E7 was conjugated to nanofibrous meshes. After 3 months, H-E assessment and specific staining of collagen type I, II, and III showed direct ligament-bone insertion with typical four zones (bone, calcified fibrocartilage, fibrocartilage, and ligament in bioactive scaffold reconstruction group. Diameters of bone tunnel were smaller in nanofibrous scaffold conjugated E7 peptide group than those in control group. The failure load of substitution complex also indicated a stronger ligament-bone insertion healing using bioactive scaffold. In conclusion, lattice-like nanofibrous scaffold with specific MSCs affinity peptide has great potential in promoting early stage of ligament-bone healing after ACL reconstruction.

  4. An uncommon cause of chest pain - penetrating atherosclerotic aortic ulcer

    OpenAIRE

    Kyaw, Htoo; Sadiq, Sanah; Chowdhury, Arnab; Gholamrezaee, Rashin; Yoe, Linus

    2016-01-01

    Chest pain is a very common symptom and can be of cardiac or non-cardiac origin. It accounts for approximately 5.5 million annual emergency room visits in the United States, according to 2011 CDC data. Penetrating atherosclerotic aortic ulcer (PAU), an uncommon condition, is also a potential cause of chest pain. We here report the case of a 65-year-old woman who presented with atypical chest and back pain. The pain persisted for 4 weeks necessitating two emergency room visits. Initial tests w...

  5. Atherosclerotic plaque detection by confocal Brillouin and Raman microscopies

    Science.gov (United States)

    Meng, Zhaokai; Basagaoglu, Berkay; Yakovlev, Vladislav V.

    2015-02-01

    Atherosclerosis, the development of intraluminal plaque, is a fundamental pathology of cardiovascular system and remains the leading cause of morbidity and mortality worldwide. Biomechanical in nature, plaque rupture occurs when the mechanical properties of the plaque, related to the morphology and viscoelastic properties, are compromised, resulting in intraluminal thrombosis and reduction of coronary blood flow. In this report, we describe the first simultaneous application of confocal Brillouin and Raman microscopies to ex-vivo aortic wall samples. Such a non-invasive, high specific approach allows revealing a direct relationship between the biochemical and mechanical properties of atherosclerotic tissue.

  6. ADIPONECTIN LEVELS AND ATHEROSCLEROTIC RISK FACTORS IN CHILDREN ON HEMODIALYSIS

    International Nuclear Information System (INIS)

    Atherosclerotic cardiovascular disease (ACVD) is the major cause of mortality in patients with end stage renal disease (ESRD) treated with hemodialysis (HD), even in children. Adiponectin (ADPN) is an adipocyte derived plasma protein having anti-atherogenic properties. ADPN levels are elevated in ESRD but it has been reported that ESRD patients with low plasma ADPN levels have a high risk of cardiovascular death. The aim of this study is to evaluate the relation between ADPN and atherosclerotic risk factors in children on hemodialysis.Twenty-eight children (17 boys and 11girls) with a mean age of 10.6 ± 3.34 years undergoing hemodialysis (HD) for a mean period of 11.96 ± 8.32 months (ranged from 6 to 36 months) and 10 healthy age and sex matched control subjects were enrolled in this study. The acute effect of a hemodialysis session on serum ADPN and other atherosclerotic risk factors , including blood pressure, serum lipids, C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were assessed by comparison of pre- and post-hemodialysis determinations. Serum levels of ADPN and TNF-α were measured by enzyme linked immunosorbant assay (ELISA) while CRP was measured by the semi-quantitative latex agglutination assay.The data showed that serum ADPN levels were twice higher in the HD group as compared to the control subjects. Concerning the atherosclerotic risk factors, TNF-α, CRP and triglycerides levels showed significant elevation in the HD group. Meanwhile, serum albumin, cholesterol and phosphorus levels showed significant decreases. The linear regression analysis showed that adiponectin was negatively correlated with glomerular filtration rate (GFR) (r = -0.68,P < 0.0001), and body mass index (r = -0.73, P < 0.0007); ADPN levels are directly related to HDL cholesterol levels (r = 0.76, P < 0.0001) and inversely related to triglycerides level (r = -0.63, P < 0.0003). No relationship was found between adiponectin and CRP.It could be concluded that

  7. Functional tissue engineering of ligament healing

    Directory of Open Access Journals (Sweden)

    Hsu Shan-Ling

    2010-05-01

    Full Text Available Abstract Ligaments and tendons are dense connective tissues that are important in transmitting forces and facilitate joint articulation in the musculoskeletal system. Their injury frequency is high especially for those that are functional important, like the anterior cruciate ligament (ACL and medial collateral ligament (MCL of the knee as well as the glenohumeral ligaments and the rotator cuff tendons of the shoulder. Because the healing responses are different in these ligaments and tendons after injury, the consequences and treatments are tissue- and site-specific. In this review, we will elaborate on the injuries of the knee ligaments as well as using functional tissue engineering (FTE approaches to improve their healing. Specifically, the ACL of knee has limited capability to heal, and results of non-surgical management of its midsubstance rupture have been poor. Consequently, surgical reconstruction of the ACL is regularly performed to gain knee stability. However, the long-term results are not satisfactory besides the numerous complications accompanied with the surgeries. With the rapid development of FTE, there is a renewed interest in revisiting ACL healing. Approaches such as using growth factors, stem cells and scaffolds have been widely investigated. In this article, the biology of normal and healing ligaments is first reviewed, followed by a discussion on the issues related to the treatment of ACL injuries. Afterwards, current promising FTE methods are presented for the treatment of ligament injuries, including the use of growth factors, gene delivery, and cell therapy with a particular emphasis on the use of ECM bioscaffolds. The challenging areas are listed in the future direction that suggests where collection of energy could be placed in order to restore the injured ligaments and tendons structurally and functionally.

  8. Healing responses following cryothermic and hyperthermic tissue ablation

    Science.gov (United States)

    Godwin, Braden L.; Coad, James E.

    2009-02-01

    Minimally invasive, thermally ablative, interventional technologies have been changing the practice of medicine since before the turn of the 20th century. More recently, cryothermic and hyperthermic therapies have expanded in terms of their spectrum of thermal generators, modes for controlling and monitoring the treatment zone and both benign and malignant medical applications. The final tissue, and hence clinical outcome, of a thermal ablation is determined by the summation of direct primary (thermal) and secondary (apoptosis, ischemia, free radical, inflammation, wound healing, etc.) injury followed by possible cellular regeneration and scar formation. The initial thermal lesion can be broadly divided into two major zones of cellular death: 1) the complete ablation zone closer to the thermal source and 2) the peripheral transition zone with a decreasing gradient of cell death. While not applicable to cryotherapy, hyperthermic complete ablation zones are subdivided into two zones: 1) thermal or heat fixation and 2) coagulative necrosis. It is important to clearly differentiate these tissue zones because of their substantially different healing responses. Therefore, the development of clinically successful thermal therapies requires an understanding of tissue healing responses. The healing responses can be affected by a number of additional factors such as the tissue's anatomy, organ specific healing differences, blood supply, protein vs. lipid content, and other factors. Thus, effective biomedical instrument development requires both an understanding of thermal cell injury/death and the body's subsequent healing responses. This paper provides a general overview of the healing pathways that follow thermal tissue treatment.

  9. Characterization and role of the immune response during ligament healing

    Science.gov (United States)

    Chamberlain, Connie S.

    inflammation and stimulating remodeling. IL-4 dose- and time-dependently stimulated early ligament regeneration but was unable to maintain the response during later healing. In summary, this work demonstrated the association between the immune cells and ligament healing, indicating a potential for obtaining a more regenerative response by modulating the immune response in a time, dose, and spatial manner.

  10. Effects of genistein on early-stage cutaneous wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eunkyo [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lee, Seung Min [Research Institute of Health Sciences, Korea University, Seoul 136-701 (Korea, Republic of); Jung, In-Kyung [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lim, Yunsook [Department of Foods and Nutrition, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kim, Jung-Hyun, E-mail: jjhkim@cau.ac.kr [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of)

    2011-07-08

    Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results

  11. Effects of genistein on early-stage cutaneous wound healing

    International Nuclear Information System (INIS)

    Highlights: → We examine the effect of genistein on cutaneous wound healing. → Genistein enhanced wound closure during the early stage of wound healing. → These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-κB and TNF-α expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results suggest that genistein

  12. Self-healing biomaterials(3)

    OpenAIRE

    Brochu, Alice B. W.; Craig, Stephen L.; Reichert, William M.

    2010-01-01

    The goal of this review is to introduce the biomaterials community to the emerging field of self-healing materials, and also to suggest how one could utilize and modify self-healing approaches to develop new classes of biomaterials. A brief discussion of the in vivo mechanical loading and resultant failures experienced by biomedical implants is followed by presentation of the self-healing methods for combating mechanical failure. If conventional composite materials that retard failure may be ...

  13. Identification of atherosclerotic plaque components with intravascular ultrasound elastography in vivo: a Yucatan pig study.

    NARCIS (Netherlands)

    Korte, C.L. de; Sierevogel, M.J.; Mastik, F.; Strijder, C.; Schaar, J.A.; Velema, E.; Pasterkamp, G.; Serruys, P.W.; Steen, A.F.W. van der

    2002-01-01

    BACKGROUND: Intravascular ultrasound elastography assesses the local strain of the atherosclerotic vessel wall. In the present study, the potential to identify different plaque components in vivo was investigated. METHODS AND RESULTS: Atherosclerotic external iliac and femoral arteries (n=24) of 6 Y

  14. Music Healing Rituals in Thailand

    Directory of Open Access Journals (Sweden)

    Bussakorn Binson

    2015-11-01

    Full Text Available This paper discusses the music healing rituals from North, Northeast and Southern Thailand. In general, these healing rituals bring together supportive elements from the family, the community and spiritual entities with the shaman as a conductor. Shaman utilizes music in corporate the community as a whole including elicits the support from the spiritual entitles. Traditional music healing process played the role as enticement to recruit spirits, distract the patients from experiencing unpleasant in their body. Even in today’s modern society these healing rituals have persisted, as they are inseparable from these regions’ animistic beliefs system.

  15. Rapid self-healing hydrogels

    Science.gov (United States)

    Phadke, Ameya; Zhang, Chao; Arman, Bedri; Hsu, Cheng-Chih; Mashelkar, Raghunath A.; Lele, Ashish K.; Tauber, Michael J.; Arya, Gaurav; Varghese, Shyni

    2012-01-01

    Synthetic materials that are capable of autonomous healing upon damage are being developed at a rapid pace because of their many potential applications. Despite these advancements, achieving self-healing in permanently cross-linked hydrogels has remained elusive because of the presence of water and irreversible cross-links. Here, we demonstrate that permanently cross-linked hydrogels can be engineered to exhibit self-healing in an aqueous environment. We achieve this feature by arming the hydrogel network with flexible-pendant side chains carrying an optimal balance of hydrophilic and hydrophobic moieties that allows the side chains to mediate hydrogen bonds across the hydrogel interfaces with minimal steric hindrance and hydrophobic collapse. The self-healing reported here is rapid, occurring within seconds of the insertion of a crack into the hydrogel or juxtaposition of two separate hydrogel pieces. The healing is reversible and can be switched on and off via changes in pH, allowing external control over the healing process. Moreover, the hydrogels can sustain multiple cycles of healing and separation without compromising their mechanical properties and healing kinetics. Beyond revealing how secondary interactions could be harnessed to introduce new functions to chemically cross-linked polymeric systems, we also demonstrate various potential applications of such easy-to-synthesize, smart, self-healing hydrogels. PMID:22392977

  16. Microcalcifications in Early Intimal Lesions of Atherosclerotic Human Coronary Arteries

    Science.gov (United States)

    Roijers, Ruben B.; Debernardi, Nicola; Cleutjens, Jack P.M.; Schurgers, Leon J.; Mutsaers, Peter H.A.; van der Vusse, Ger J.

    2011-01-01

    Although calcium (Ca) precipitation may play a pathogenic role in atherosclerosis, information on temporal patterns of microcalcifications in human coronary arteries, their relation to expression of calcification-regulating proteins, and colocalization with iron (Fe) and zinc (Zn) is scarce. Human coronary arteries were analyzed post mortem with a proton microprobe for element concentrations and stained (immuno)histochemically for morphological and calcification-regulating proteins. Microcalcifications were occasionally observed in preatheroma type I atherosclerotic intimal lesions. Their abundance increased in type II, III, and IV lesions. Moreover, their appearance preceded increased expression of calcification-regulating proteins, such as osteocalcin and bone morphogenetic protein-2. In contrast, their presence coincided with increased expression of uncarboxylated matrix Gla protein (MGP), whereas the content of carboxylated MGP was increased in type III and IV lesions, indicating delayed posttranslational conversion of biologically inactive into active MGP. Ca/phosphorus ratios of the microcalcifications varied from 1.6 to 3.0, including amorphous Ca phosphates. Approximately 75% of microcalcifications colocalized with the accumulation of Fe and Zn. We conclude that Ca microprecipitation occurs in the early stages of atherosclerosis, inferring a pathogenic role in the sequel of events, resulting in overt atherosclerotic lesions. Microcalcifications may be caused by local events triggering the precipitation of Ca rather than by increased expression of calcification-regulating proteins. The high degree of colocalization with Fe and Zn suggests a mutual relationship between these trace elements and early deposition of Ca salts. PMID:21531376

  17. Clinical Study of Acoustic Densitometry Technique in Detecting Atherosclerotic Plaque

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective: To investigate the effect of Quyu Xiaoban Capsule (祛瘀消斑, QYXB) on the regressive treatment of atherosclerosis (AS) with acoustic densitometry (AD) technique. Methods: Eighty patients with AS were randomly divided into two groups, trial group was treated with QYXB and conventional medicine, and control group was treated with conventional medicine alone. Normal arterial wall and different types of atherosclerotic plaques were detected with AD technique before treatment and 10 months later. Resuits: The corrected averages in intimal echo intensity (AIIc%) were elevated in both groups but without significant difference, AIIc% of fatty plaques were increased in both groups and the value after treatment was significantly higher than that of pre-treatment in the trial group (68.12±5.54 vs 61.43±5.37, P<0.05).The increment rate of AIIc% in trial group was significantly higher than that in control group (10.9±5.1% vs2.5±5.5%, P<0.05). Conclusion: QYXB can stabilize the atherosclerotic plaque by increasing its acoustic density. Acoustic densitometry technique can differentiate the different histological plaques and monitor the histological changes of plaques during treatment.

  18. CO2 vascular anastomosis of atherosclerotic and calcified arteries

    Science.gov (United States)

    White, John V.; Leefmans, Eric; Stewart, Gwendolyn J.; Katz, Mira L.; Comerota, Anthony J.

    1990-06-01

    The technique for CO2 laser fusion vascular anastomosis in normal vessels has been well established. Normal arterial wall has a predictable thermal response to the incident laser energy, with rapid heating and cooling of collagen within the arterial wall. Since atherosclerosis involves subendothelial cellular proliferation, lipid and calcium deposition, it may modify the thermal responsiveness of the arterial wall. To this study, CO2 laser fusion anastomoses were attempted in rabbits with non-calcific atherosclerosis and humans with calcific atherosclerosis. All anastomoses were successfully completed without alteration in technique despite the presence of plaque at the site of laser fusion. Histology of rabbit vessels revealed the classic laser fusion cap within the adventitia and persistent atherosclerotic plaque at the flow surface. Duplex imaging of patients post-operatively demonstrated long term anastomotic patency in 2 of 3 fistulae. These results suggest that neither non-calcified or calcified atherosclerosis significantly alters the arterial wall thermal responsiveness to CO2 laser energy or inhibits creation of laser fusion anastomoses. Therefore, this technique may be applicable to the treatment of patients with atherosclerotic occlusive disease.

  19. Tensile and compressive properties of fresh human carotid atherosclerotic plaques.

    LENUS (Irish Health Repository)

    Maher, Eoghan

    2009-12-11

    Accurate characterisation of the mechanical properties of human atherosclerotic plaque is important for our understanding of the role of vascular mechanics in the development and treatment of atherosclerosis. The majority of previous studies investigating the mechanical properties of human plaque are based on tests of plaque tissue removed following autopsy. This study aims to characterise the mechanical behaviour of fresh human carotid plaques removed during endarterectomy and tested within 2h. A total of 50 radial compressive and 17 circumferential tensile uniaxial tests were performed on samples taken from 14 carotid plaques. The clinical classification of each plaque, as determined by duplex ultrasound is also reported. Plaques were classified as calcified, mixed or echolucent. Experimental data indicated that plaques were highly inhomogeneous; with variations seen in the mechanical properties of plaque obtained from individual donors and between donors. The mean behaviour of samples for each classification indicated that calcified plaques had the stiffest response, while echolucent plaques were the least stiff. Results also indicated that there may be a difference in behaviour of samples taken from different anatomical locations (common, internal and external carotid), however the large variability indicates that more testing is needed to reach significant conclusions. This work represents a step towards a better understanding of the in vivo mechanical behaviour of human atherosclerotic plaque.

  20. Spectral CT of carotid atherosclerotic plaque: comparison with histology

    International Nuclear Information System (INIS)

    To distinguish components of vulnerable atherosclerotic plaque by imaging their energy response using spectral CT and comparing images with histology. After spectroscopic calibration using phantoms of plaque surrogates, excised human carotid atherosclerotic plaques were imaged using MARS CT using a photon-processing detector with a silicon sensor layer and microfocus X-ray tube (50 kVp, 0.5 mA) at 38-μm voxel size. The plaques were imaged, sectioned and re-imaged using four threshold energies: 10, 16, 22 and 28 keV; then sequentially stained with modified Von Kossa, Perl's Prussian blue and Oil-Red O, and photographed. Relative Hounsfield units across the energies were entered into a linear algebraic material decomposition model to identify the unknown plaque components. Lipid, calcium, iron and water-like components of plaque have distinguishable energy responses to X-ray, visible on spectral CT images. CT images of the plaque surface correlated very well with histological photographs. Calcium deposits (>1,000 μm) in plaque are larger than iron deposits (<100 μm), but could not be distinguished from each other within the same voxel using the energy range available. Spectral CT displays energy information in image form at high spatial resolution, enhancing the intrinsic contrast of lipid, calcium and iron within atheroma. (orig.)

  1. Surgical treatment of penetrating atherosclerotic ulcer of the descending aorta

    Directory of Open Access Journals (Sweden)

    Kovačević Pavle

    2013-01-01

    Full Text Available Introduction. The term “penetrating atherosclerotic ulcer” (PAU of the aorta describes the condition in which ulceration of an aortic atherosclerotic lesion penetrates the internal elastic lamina into media. PAU is a high-risk lesion due to its deleterious effects on the integrity of aortic wall, with potentially fatal outcome. Case report. A patient with intensive, sharp chest pain irradiating to the back but with no signs of myocardial ischemia on an electrocardiogram was referred to our hospital. Transthoracic echocardiography showed no pathological changes of the ascending aorta. However, multislice computed tomography (CT showed an aortic ulcer with varying degree of the subadventitial hemorrhage in the region of the thoracic aorta at the level of Th 8-9. Due to imminent rupture of the penetrating aortic ulcer, the patient was promptly prepared for surgery. A 15 cm long subadventitial hematoma was found intraoperatively in the right posterolateral aspect of the descending aorta, 5 cm above the diaphragm and 7 cm below the origin of the left subclavial artery. The affected segment of the aorta was resected, followed by an inlay aortic reconstruction with a Dacron tube graft of 24 mm. Control CT revealed satisfactory reconstruction of the descending aorta. Conclusion. PAU is a rare, but potentially fatal disease. Open surgery in patients with PAU is an effective treatment strategy, although endovascular treatment options are emerging.

  2. Innovation and wound healing.

    Science.gov (United States)

    Harding, Keith

    2015-04-01

    Innovation in medicine requires unique partnerships between academic research, biotech or pharmaceutical companies, and health-care providers. While innovation in medicine has greatly increased over the past 100 years, innovation in wound care has been slow, despite the fact that chronic wounds are a global health challenge where there is a need for technical, process and social innovation. While novel partnerships between research and the health-care system have been created, we still have much to learn about wound care and the wound-healing processes.

  3. Self-Healing Computation

    OpenAIRE

    Saad, George; Saia, Jared

    2014-01-01

    In the problem of reliable multiparty computation (RC), there are $n$ parties, each with an individual input, and the parties want to jointly compute a function $f$ over $n$ inputs. The problem is complicated by the fact that an omniscient adversary controls a hidden fraction of the parties. We describe a self-healing algorithm for this problem. In particular, for a fixed function $f$, with $n$ parties and $m$ gates, we describe how to perform RC repeatedly as the inputs to $f$ change. Our al...

  4. Clopidogrel delays gastric ulcer healing in rats.

    Science.gov (United States)

    Luo, Jiing-Chyuan; Huo, Teh-Ia; Hou, Ming-Chih; Lin, Hsiao-Yi; Li, Chung-Pin; Lin, Han-Chieh; Chang, Full-Young; Lee, Fa-Yauh

    2012-11-15

    Clopidogrel is not safe enough for the gastric mucosa in patients with high risk of peptic ulcer. This study aimed to explore if clopidogrel delays gastric ulcer healing and elucidate the involved mechanisms. Gastric ulcer was induced in rats and the ulcer size, mucosal epithelial cell proliferation of the ulcer margin, expression of growth factors [epidermal growth factor (EGF), basic fibroblast growth factor] and their receptors, and signal transduction pathways for cell proliferation were measured and compared between the clopidogrel-treated group and untreated controls. For the in vitro part, rat gastric mucosal epithelial cell line (RGM-1 cells) was used to establish EGF receptor over-expressed cells. Cell proliferation and molecular change under EGF treatment (10ng/ml) with and without clopidogrel (10(-6)M) were demonstrated. Ulcer size was significantly larger in the clopidogrel-treated group compared to the control and mucosal epithelial cell proliferation of the ulcer margin was significantly decreased in the clopidogrel-treated group (Pulcer-induced gastric epithelial cell proliferation and ulcer-stimulated expressions of EGF receptor and phosphorylated extracellular signal-regulated kinase (PERK) at the ulcer margin (Pgastric ulcer healing in rats via inhibiting gastric epithelial cell proliferation, at least by inhibition of the EGF receptor-ERK signal transduction pathway.

  5. Matrix metalloproteinases in impaired wound healing

    OpenAIRE

    auf dem Keller, Ulrich

    2015-01-01

    Fabio Sabino, Ulrich auf dem Keller Institute of Molecular Health Sciences, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland Abstract: Cutaneous wound healing is a complex tissue response that requires a coordinated interplay of multiple cells in orchestrated biological processes to finally re-establish the skin's barrier function upon injury. Proteolytic enzymes and in particular matrix metalloproteinases (MMPs) contribute to all phas...

  6. Tendon, tendon healing, hyperlipidemia and statins

    Science.gov (United States)

    Esenkaya, Irfan; Unay, Koray

    2011-01-01

    Summary Both hyperlipidemia and metabolic syndrome have adverse effect on tendon structure. Atorvastatin is most widely used antihyperlipidemic drug. Statins have adverse effects on the tendon. Many studies have analyzed the relationship between atorvastatin and skeletal muscles. Atorvastatin administered after the surgical repair of a ruptured tendon appears to affect revascularization, collagenization, inflammatory cell infiltration, and collagen construction. Therefore, further investigations on the effects of atorvastatin on tendon healing are needed. PMID:23738266

  7. PEG modification on 111In-labeled phosphatidyl serine liposomes for imaging of atherosclerotic plaques

    International Nuclear Information System (INIS)

    Introduction: Previously, we reported a probe for imaging of atherosclerotic plaques: 111In-labeled liposomes. Liposomes were modified with phosphatidylserine (PS) because macrophages recognize PS and phagocytize apoptotic cells in plaques. PS modification was successful and we could visualize atherosclerotic plaques by single-photon emission computed tomography (SPECT). However, too-rapid blood clearance reduced accumulation of PS-liposomes in plaques in vivo. Therefore, in the present study, PS-liposomes were modified with polyethylene glycol (PEG) to retard the rate of blood clearance. Methods: PS-liposomes (size, 100 nm or 200 nm) were PEGylated with PEG2000 or PEG5000 at 1 or 5 mol%, and radiolabeled with 111In. For the study of uptake in vitro, liposomes were incubated with mouse peritoneal macrophages. Biodistribution studies in vivo were carried out in ddY mice. En face autoradiograms were obtained with apoE−/− mice upon intravenous injection of 111In-liposomes. Results: Uptake was decreased significantly at 5 mol% PEGylation in 100-nm PS-liposomes (*P < 0.05 vs. 0 mol%). All the PEGylated liposomes tested showed significantly lower uptake than the non-PEGylated control in 200-nm liposomes. In vivo results showed slower blood clearance in PEGylated liposomes. Autoradiograms in apoE−/− mice were well matched with Oil Red O staining. Additionally, 200-nm PS-liposomes modified with 5%PEG2000 ([111In]5%PEG2000PS200) showed the highest uptake to the region in vivo. Conclusions: As expected, PEGylation retarded the rate of blood clearance. In addition, it affected liposome uptake by macrophages in vitro. These results suggest that the balance between the rate of blood clearance and macrophage recognition is important, and [111In]5%PEG2000PS200 showed the best results in our investigation

  8. Neovascularization and coronary atherosclerotic plaque: cinematographic localization and quantitative histologic analysis.

    Science.gov (United States)

    Kamat, B R; Galli, S J; Barger, A C; Lainey, L L; Silverman, K J

    1987-10-01

    A new technique was developed for analyzing the neovascularization associated with coronary artery atherosclerosis: cinematography during silicone polymer injection of the coronary arteries of fixed and cleared human hearts, followed by histologic analysis in routine and 1-micron-thick, Epon-embedded sections. Twenty-two hearts obtained at autopsy were studied. On the basis of cinematographic findings, individual regions of the coronary arteries were classified as negative, positive, or abundantly positive for neovascularization. Positive and abundantly positive areas, which invariably occurred in segments exhibiting changes of atherosclerosis, contained numerous small vessels in the adventitia and outer media (4.7 +/- 1.5 and 9.8 +/- 1.3 [SE] vessel profiles/artery cross-section in positive and abundantly positive areas, versus 1.0 +/- 0.6 in negative regions). Abundantly positive areas, which occurred in coronary artery segments demonstrating the most extensive atherosclerotic change, contained numerous small vessels in the inner media or in the plaque itself. Some of these microvessels were in close proximity to mast cells, which represent potentially rich sources of mediators affecting vascular tone and permeability. Vessels were not observed in the inner media or in atherosclerotic plaque in areas designated either positive or negative by cinematography. These findings show how our approach can be used both to define the three-dimensional, in situ configuration of coronary artery neovascularization and to characterize the histology of this process in detail. They also confirm previous work indicating that areas of coronary arteries involved by atherosclerosis frequently exhibit extensive neovascularization. PMID:2443438

  9. HMGB1 induces secretion of matrix vesicles which participate in microcalcification of atherosclerotic plaques

    Institute of Scientific and Technical Information of China (English)

    CHEN Qiang; BEI Jun-jie; LIU Chuan; FENG Shi-bin; ZHAO Wei-bo; ZHOU Zhou; YU Zheng-ping; DU Xiao-jun; HU Hou-yuan

    2016-01-01

    AIM:Early calcification of atherosclerotic plaques are colocalized with macrophage and high mobility group box 1 (HMGB1), a cytokine associated with biomineralizing process under physiological and pathological conditions .Our study aims to evaluate whether HMGB1 induces ectopic mineralization via promoting the secretion of matrix vesicles ( MVs) from macrophages .METHODS:HMGB1 was added to the medium of macrophages , the secretion of MVs in the supernatant was tested by flow cytometry analysis .The mineral deposition in calcifying medium was detected by Alizarin Red staining and von Kossa staining .Transmission electron microscopy showed the formation of hydroxyapatite crystals in MVs .Then we subcutaneous injection into mice with MVs to induce regional minera-lization.RESULTS:HMGB1 significantly promoted secretion of MVs from macrophages as raveled by flow cytometry analysis .TNAP activity, considered as a marker of MVs maturation , was higher in HMGB1-induced MVs compared to the control-MVs.HMGB1-MVs also led to mineral deposition in an in vitro MVs-collagen mineralization model .Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization .Mechanistic experiments revealed that HMGB 1 activated neutral sphingomyelinase 2 ( nSMase2 ) that involved the receptor for advanced glycation end products ( RAGE ) and p38 MAPK (upstream of nSMase2).Inhibition of nSMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and min-eral deposition .CONCLUSIONS: HMGB1 induces MVs secretion from macrophages at least in part , via the RAGE/p38 MAPK/nSMase2 signaling pathway .Our findings thus reveal a novel mechanism by which HMGB 1 may participated in the early calcification of atherosclerotic plaques .

  10. Investigating the role of acellular skin substitutes in wound healing

    OpenAIRE

    Greaves, Nicholas Stuart

    2015-01-01

    After cutaneous injury, wound healing is an essential process that restores barrier and homeostatic function to the skin. Tissue restoration is classically grouped into four phases, involving the dynamic, regulated and sequential interaction of multiple cells types, effector molecules and extracellular matrix components. While most wounds heal in a timely fashion, local and systemic factors can prevent wound resolution resulting in chronic wound formation. Examples include diabetic and venous...

  11. Role of mathematical modeling in bone fracture healing

    OpenAIRE

    Pivonka, Peter; Colin R Dunstan

    2012-01-01

    Bone fracture healing is a complex physiological process commonly described by a four-phase model consisting of an inflammatory phase, two repair phases with soft callus formation followed by hard callus formation, and a remodeling phase, or more recently by an anabolic/catabolic model. Data from humans and animal models have demonstrated crucial environmental conditions for optimal fracture healing, including the mechanical environment, blood supply and availability of mesenchymal stem cells...

  12. Abnormal pigmentation within cutaneous scars: a complication of wound healing

    OpenAIRE

    Sarah Chadwick; Rebecca Heath; Mamta Shah

    2012-01-01

    Abnormally pigmented scars are an undesirable consequence of cutaneous wound healing and are a complication every single individual worldwide is at risk of. They present a challenge for clinicians, as there are currently no definitive treatment options available, and render scars much more noticeable making them highly distressing for patients. Despite extensive research into both wound healing and the pigment cell, there remains a scarcity of knowledge surrounding the repigmentation of cutan...

  13. Clinical Application of Growth Factors and Cytokines in Wound Healing

    OpenAIRE

    Barrientos, Stephan; Brem, Harold; Stojadinovic, Olivera; Tomic-Canic, Marjana

    2014-01-01

    Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of non-healing wounds (e.g. pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted a nonline search of Medline and Pub Medical and crit...

  14. Healing agent for self-healing cementious material

    NARCIS (Netherlands)

    Jonkers, H.M.

    2011-01-01

    The invention provides a process for the production of a cementious material. The process comprises mixing cement starting materials and a particulate healing agent to provide the cementious material. The healing agent comprises coated particles, wherein the coated particles comprise bacterial mater

  15. 黄芪对动脉粥样硬化兔骨髓内皮祖细胞生长的影响响%Effect of astragalus mongholicus on the growth of endothelial progenitor cells from bone marrow of atherosclerotic rabbits

    Institute of Scientific and Technical Information of China (English)

    李蕾; 张怀勤; 尹娟; 范旰; 陈骁

    2011-01-01

    Objective To investigate the effect of astragalus mongholicus on the growth of endothelial progenitor cells from bone marrow of atherosclerotic rabbits, and to investigate the potential of astragalus for treatment of coronary heart disease. Methods New Zealand white rabbits were randomly divided into the control group (n= 6) and the atherosclerosis group (n = 6) to establish animal models of atherosclerosis. EPCs were cultured and identified by Dil-Ac-LDL uptake and FITC-UEA-I-lectin binding using fluorescence microscopy (FM). The ability of tube structure formation of EPCs were assessed using matrigel reagent kit in vitro. The adhesion, migration and proliferation ability of EPCs were also measured in these two groups. Results Plaques and fatty streak leisions, which were positive for DiI-ac-LDL-uptaking and FITC-UEA-I-lectin staining, could be observed in coronary arteries from rabbit models of atherosclerosis. Capillary formation could be observed 6 days post EPCs culturing. Compared with those in the control group, the cell number, the adhesion, migration and proliferation abilities of EPCs decreased significantly in the atherosclerosis group (P < 0.05); Astragalus could significantly increase the EPCs number and the adhesion, migration and proliferation abilities of EPCs at 20 g/L (P < 0.05) than other dosage. Conclusion The potential mechanism for Astragalus as a treatment of coronary artery disease is its contribution to EPCs growth.%目的:研究黄芪对冠状动脉粥样硬化模型兔骨髓内皮祖细胞(endothelial lprogenitor rcells,,EPCs) )生长的影响,并探讨黄芪对冠心病临床治疗的可能机制.方法:建立动脉粥样硬化模型,分为正常对照组和动脉粥样硬化组,体外分离培养EPCs,通过荧光显微镜观察细胞经乙酰化低密度脂蛋白(DiI-ac-LDL) )摄取试验和荆豆凝集素(FITC-UEA-I)和体外成血管试剂matrigel l观察细胞成血管功能来鉴定EPCs,检测细胞黏附能力、迁移能力

  16. Our Pathway toward Healing Racism

    Science.gov (United States)

    Honour, Robert

    2013-01-01

    In this article, Robert Honour, Training and Staff Development Manager, at the Fairfax, Virginia, Department of Family Services (DFS), reports on the outcome of "Healing Racism" training at his organization. Participants in "Healing Racism Institutes" are transforming relationships and creating an organizational culture that…

  17. Self-Healing Laminate System

    Science.gov (United States)

    Beiermann, Brett A. (Inventor); Keller, Michael W. (Inventor); White, Scott R. (Inventor); Sottos, Nancy R. (Inventor)

    2016-01-01

    A laminate material may include a first flexible layer, and a self-healing composite layer in contact with the first flexible layer. The composite layer includes an elastomer matrix, a plurality of first capsules including a polymerizer, and a corresponding activator for the polymerizer. The laminate material may self-heal when subjected to a puncture or a tear.

  18. Self-healing biomaterials(3)

    Science.gov (United States)

    Brochu, Alice B. W.; Craig, Stephen L.; Reichert, William M.

    2010-01-01

    The goal of this review is to introduce the biomaterials community to the emerging field of self-healing materials, and also to suggest how one could utilize and modify self-healing approaches to develop new classes of biomaterials. A brief discussion of the in vivo mechanical loading and resultant failures experienced by biomedical implants is followed by presentation of the self-healing methods for combating mechanical failure. If conventional composite materials that retard failure may be considered zeroth generation self-healing materials, then taxonomically-speaking, first generation self-healing materials describe approaches that “halt” and “fill” damage, whereas second generation self-healing materials strive to “fully restore” the pre-failed material structure. In spite of limited commercial use to date, primarily because the technical details have not been suitably optimized, it is likely from a practical standpoint that first generation approaches will be the first to be employed commercially, whereas second generation approaches may take longer to implement. For self-healing biomaterials the optimization of technical considerations is further compounded by the additional constraints of toxicity and biocompatibility, necessitating inclusion of separate discussions of design criteria for self-healing biomaterials. PMID:21171168

  19. Management of impaired fracture healing: Historical aspects

    OpenAIRE

    Gajdobranski Đorđe; Micić Ivan; Mitković Milorad B.; Mladenović Desimir; Milankov Miroslav

    2005-01-01

    Introduction Establishing continuity of long bones in cases of impaired bone healing and pseudo-arthrosis is one of the most complex problems in orthopedics. Impaired bone healing The problem of impaired fracture healing is not new. As in other areas of human life, the roots of modern treatment of impaired bone healing lie in ancient medicine. A relatively high percentage of impaired bone healing, as well as unsatisfactory results of standard therapies of impaired bone healing and pseudoarthr...

  20. Synthetic Self-Healing Methods

    Energy Technology Data Exchange (ETDEWEB)

    Bello, Mollie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-06-02

    Given enough time, pressure, temperature fluctuation, and stress any material will fail. Currently, synthesized materials make up a large part of our everyday lives, and are used in a number of important applications such as; space travel, under water devices, precise instrumentation, transportation, and infrastructure. Structural failure of these material scan lead to expensive and dangerous consequences. In an attempt to prolong the life spans of specific materials and reduce efforts put into repairing them, biologically inspired, self-healing systems have been extensively investigated. The current review explores recent advances in three methods of synthesized self-healing: capsule based, vascular, and intrinsic. Ideally, self-healing materials require no human intervention to promote healing, are capable of surviving all the steps of polymer processing, and heal the same location repeatedly. Only the vascular method holds up to all of these idealities.

  1. Recent advances on the association of apoptosis in chronic non healing diabetic wound

    Institute of Scientific and Technical Information of China (English)

    Awadhesh; K; Arya; Richik; Tripathi; Santosh; Kumar; Kamlakar; Tripathi

    2014-01-01

    Generally, wounds are of two categories, such as chronic and acute. Chronic wounds takes time to heal when compared to the acute wounds. Chronic wounds include vasculitis, non healing ulcer, pyoderma gangrenosum, and diseases that cause ischemia. Chronic wounds are rapidly increasing among the elderly population with dysfunctional valves in their lower extremity deep veins, ulcer, neuropathic foot and pressure ulcers. The process of the healing of wounds has several steps with the involvement of immune cells and several other cell types. There are many evidences supporting the hypothesis that apoptosis of immune cells is involved in the wound healing process by ending inflammatory condition. It is also involved in the resolution of various phases of tissue repair. During final steps of wound healing most of the endothelial cells, macrophagesand myofibroblasts undergo apoptosis or exit from the wound, leaving a mass that contains few cells and consists mostly of collagen and other extracellular matrix proteins to provide strength to the healing tissue. This review discusses the various phases of wound healing both in the chronic and acute wounds especially during diabetes mellitus and thus support the hypothesis that the oxidative stress, apoptosis, connexins and other molecules involved in the regulation of chronic wound healing in diabetes mellitus and gives proper understanding of the mechanisms controlling apoptosis and tissue repair during diabetes and may eventually develop therapeutic modalities to fasten the healing process in diabetic patients.

  2. Unveiling Cebuano Traditional Healing Practices

    Directory of Open Access Journals (Sweden)

    ZachiaRaiza Joy S. Berdon

    2016-02-01

    Full Text Available This study aims to identify the features of Cebuano’s traditional healing practices. Specifically, it also answers the following objectives: analyze traditional healing in Cebuano’s perspectives, explain the traditional healing process practiced in terms of the traditional healers’ belief, and extrapolate perceptions of medical practitioners toward traditional healing. This study made use of qualitative approach, among five traditional healers who performed healing for not less than ten years, in the mountain barangays of Cebu City. These healers served as the primary informants who were selected because of their popularity in healing. The use of open-ended interview in local dialect and naturalistic observation provided a free listing of their verbatim accounts were noted and as primary narratives. Participation in the study was voluntary and participants were interviewed privately after obtaining their consent. The Cebuano traditional healing practices or “panambal” comprise the use of “himolso” (pulse-checking, “palakaw” (petition, “pasubay” (determining what causes the sickness and its possible means of healing, “pangalap” (searching of medicinal plants for “palina” (fumigation, “tayhop” (gentle-blowing, “tutho” (saliva-blowing,“tuob” (boiling, “orasyon” (mystical prayers, “hilot” (massage, and “barang” (sorcery. Though traditional with medical science disapproval, it contributes to a mystical identity of Cebuano healers, as a manifestation of folk Catholicism belief, in order to do a good legacy to the community that needs help. For further study, researchers may conduct further the studies on the: curative effects of medicinal plants in Cebu, psychological effect pulsechecking healed persons by the mananambal, and unmasking the other features of traditional healing.

  3. Effect of fibroblast-seeded artificial dermis on wound healing.

    Science.gov (United States)

    Jang, Joon Chul; Choi, Rak-Jun; Han, Seung-Kyu; Jeong, Seong-Ho; Kim, Woo-Kyung

    2015-04-01

    In covering wounds, efforts should include use of the safest and least invasive methods with a goal of achieving optimal functional and cosmetic outcome. The recent development of advanced technology in wound healing has triggered the use of cells and/or biological dermis to improve wound healing conditions. The purpose of the study was to evaluate the effects of fibroblast-seeded artificial dermis on wound healing efficacy.Ten nude mice were used in this study. Four full-thickness 6-mm punch wounds were created on the dorsal surface of each mouse (total, 40 wounds). The wounds were randomly assigned to one of the following 4 treatments: topical application of Dulbecco phosphate-buffered saline (control), human fibroblasts (FB), artificial dermis (AD), and human fibroblast-seeded artificial dermis (AD with FB). On the 14th day after treatment, wound healing rate and wound contraction, which are the 2 main factors determining wound healing efficacy, were evaluated using a stereoimage optical topometer system, histomorphological analysis, and immunohistochemistry.The results of the stereoimage optical topometer system demonstrated that the FB group did not have significant influence on wound healing rate and wound contraction. The AD group showed reduced wound contraction, but wound healing was delayed. The AD with FB group showed decreased wound contraction without significantly delayed wound healing. Histomorphological analysis exhibited that more normal skin structure was regenerated in the AD with FB group. Immunohistochemistry demonstrated that the AD group and the AD with FB group produced less α-smooth muscle actin than the control group, but this was not shown in the FB group.Fibroblast-seeded artificial dermis may minimize wound contraction without significantly delaying wound healing in the treatment of skin and soft tissue defects.

  4. Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism.

    Science.gov (United States)

    Abela, Oliver G; Ahsan, Chowdhury H; Alreefi, Fadi; Salehi, Negar; Baig, Imran; Janoudi, Abed; Abela, George S

    2016-06-01

    Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis-often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy. PMID:27091328

  5. Radiotherapy and wound healing.

    Science.gov (United States)

    Devalia, Haresh L; Mansfield, Lucy

    2008-03-01

    This review article discusses basic radiation physics and effects of radiation on wounds. It examines various postulated hypothesis on the role of circulatory decrease and radiation-induced direct cellular damage. The new concept related to the radiation pathogenesis proposes that there is a cascade of cytokines initiated immediately after the radiation. Sustained activation of myofibroblasts in the wound accounts for its chronicity. Recent advances highlight that transforming growth factor beta1 is the master switch in pathogenesis of radiation fibrosis. This articles overviews its role and summarises the available evidences related to radiation damage. The goal of this article was to provide its modern understanding, as future research will concentrate on antagonising the effects of cytokines to promote wound healing. PMID:18081782

  6. Thymosin β4 Promotes Dermal Healing.

    Science.gov (United States)

    Kleinman, H K; Sosne, G

    2016-01-01

    No agent has been identified that significantly accelerates the repair of chronic dermal wounds in humans. Thymosin beta 4 (Tβ4) is a small, abundant, naturally occurring regenerative protein that is found in body fluids and inside cells. It was found to have angiogenic and antiinflammatory activity and to be high in platelets that aggregate at the wound site. Thus we used Tβ4 initially in dermal healing. It has since been shown to have many activities important in tissue protection, repair, and regeneration. Tβ4 increases the rate of dermal healing in various preclinical animal models, including diabetic and aged animals, and is active for burns as well. Tβ4 also accelerated the rate of repair in phase 2 trials with patients having pressure ulcers, stasis ulcers, and epidermolysis bullosa wounds. It is safe and well tolerated and will likely have additional uses in the skin and in injured organs for tissue repair and regeneration. PMID:27450738

  7. Zooming in on the genesis of atherosclerotic plaque microcalcifications.

    Science.gov (United States)

    Ruiz, Jessica L; Weinbaum, Sheldon; Aikawa, Elena; Hutcheson, Joshua D

    2016-06-01

    Epidemiological evidence conclusively demonstrates that calcium burden is a significant predictor of cardiovascular morbidity and mortality; however, the underlying mechanisms remain largely unknown. These observations have challenged the previously held notion that calcification serves to stabilize the atherosclerotic plaque. Recent studies have shown that microcalcifications that form within the fibrous cap of the plaques lead to the accrual of plaque-destabilizing mechanical stress. Given the association between calcification morphology and cardiovascular outcomes, it is important to understand the mechanisms leading to calcific mineral deposition and growth from the earliest stages. We highlight the open questions in the field of cardiovascular calcification and include a review of the proposed mechanisms involved in extracellular vesicle-mediated mineral deposition. PMID:27040360

  8. Severe supraaortal atherosclerotic disease resembling Takayasu’s Arteritis

    Directory of Open Access Journals (Sweden)

    Bernhard Kis

    2007-07-01

    Full Text Available Bernhard Kis1,2, Thomas Liebig3,4, Peter Berlit11Department of Neurology, Alfried Krupp Hospital, Essen, Germany; 2Department of Psychiatry, University of Duisburg-Essen, Essen, Germany; 3Department of Neuroradiology, Alfried Krupp Hospital, Essen, Germany; 4Department of Neuroradiology, Technical University of Munich, Munich, GermanyAbstract: We report a case of a 64 year-old man whose clinical presentation and neuroimaging findings strikingly resembled those found in Takayasu’s Arteritis which is characterized by the triad of absent radial pulses, ischemic retinopathy, and carotid sinus hyperreflexia causing syncopes. Angiographically, the patient exhibited severe atherosclerotic changes of the supraaortic large vessels. Stent-assisted angioplasty resulted in both clinical improvement and increased cerebral blood flow as measured by angiography and ultrasound.Keywords: Takayasu’s arteritis, atherosclerosis, angiography, stent, angioplasty

  9. Lipid and protein maps defining arterial layers in atherosclerotic aorta

    Directory of Open Access Journals (Sweden)

    Marta Martin-Lorenzo

    2015-09-01

    Full Text Available Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. The molecular anatomy of healthy and atherosclerotic tissue is pursued to identify ongoing molecular changes in atherosclerosis development. Mass Spectrometry Imaging (MSI accounts with the unique advantage of analyzing proteins and metabolites (lipids while preserving their original localization; thus two dimensional maps can be obtained. Main molecular alterations were investigated in a rabbit model in response to early development of atherosclerosis. Aortic arterial layers (intima and media and calcified regions were investigated in detail by MALDI-MSI and proteins and lipids specifically defining those areas of interest were identified. These data further complement main findings previously published in J Proteomics (M. Martin-Lorenzo et al., J. Proteomics. (In press; M. Martin-Lorenzo et al., J. Proteomics 108 (2014 465–468. [1,2].

  10. Tools for improving the diagnosis of atherosclerotic plaque using ultrasound

    DEFF Research Database (Denmark)

    Jespersen, Søren Kragh

    1997-01-01

    topics have been investigated: an ultrasound pulse-echo simulation tool and a new compound imaging technique for improving visualization of atherosclerotic disease.A tool for simulation of the received electrical signal in a pulse-echo ultrasound system, due to a reflector surface of arbitrary geometry......, has been developed. The method is denoted the Diffraction Response Interpolation Method (DRIM) and is based on the pulse-echo diffraction impulse response method. The DRIM is a computationally efficient tool for calculating the integral of the spatially varying pulse-echo diffraction impulse response...... and experimentally. The MACI method operates by recording information about a given tissue region using a number of beam angles (typically 3 to 11) and combining the information into a single compound image (so-called spatial compounding). During the project a flexible experimental multi-channel ultrasound system...

  11. Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G

    2016-01-01

    Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need...... to reduce levels to no advice on treatment. New insight in epidemiology now suggests that these lipoproteins, marked by high triglycerides, are strong and independent predictors of ASCVD and all-cause mortality, and that their cholesterol content or remnant cholesterol likewise are strong predictors...... of ASCVD. Of all adults, 27% have triglycerides >2 mmol/L (176 mg/dL), and 21% have remnant cholesterol >1 mmol/L (39 mg/dL). For individuals in the general population with nonfasting triglycerides of 6.6 mmol/L (580 mg/dL) compared with individuals with levels of 0.8 mmol/L (70 mg/dL), the risks were 5...

  12. Lipid and protein maps defining arterial layers in atherosclerotic aorta.

    Science.gov (United States)

    Martin-Lorenzo, Marta; Balluff, Benjamin; Maroto, Aroa S; Carreira, Ricardo J; van Zeijl, Rene J M; Gonzalez-Calero, Laura; de la Cuesta, Fernando; Barderas, Maria G; Lopez-Almodovar, Luis F; Padial, Luis R; McDonnell, Liam A; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2015-09-01

    Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. The molecular anatomy of healthy and atherosclerotic tissue is pursued to identify ongoing molecular changes in atherosclerosis development. Mass Spectrometry Imaging (MSI) accounts with the unique advantage of analyzing proteins and metabolites (lipids) while preserving their original localization; thus two dimensional maps can be obtained. Main molecular alterations were investigated in a rabbit model in response to early development of atherosclerosis. Aortic arterial layers (intima and media) and calcified regions were investigated in detail by MALDI-MSI and proteins and lipids specifically defining those areas of interest were identified. These data further complement main findings previously published in J Proteomics (M. Martin-Lorenzo et al., J. Proteomics. (In press); M. Martin-Lorenzo et al., J. Proteomics 108 (2014) 465-468.) [1,2]. PMID:26217810

  13. Modulators of Macrophage Polarization Influence Healing of the Infarcted Myocardium

    Directory of Open Access Journals (Sweden)

    Ellis N. ter Horst

    2015-12-01

    Full Text Available To diminish heart failure development after acute myocardial infarction (AMI, several preclinical studies have focused on influencing the inflammatory processes in the healing response post-AMI. The initial purpose of this healing response is to clear cell debris of the injured cardiac tissue and to eventually resolve inflammation and support scar tissue formation. This is a well-balanced reaction. However, excess inflammation can lead to infarct expansion, adverse ventricular remodeling and thereby propagate heart failure development. Different macrophage subtypes are centrally involved in both the promotion and resolution phase of inflammation. Modulation of macrophage subset polarization has been described to greatly affect the quality and outcome of healing after AMI. Therefore, it is of great interest to reveal the process of macrophage polarization to support the development of therapeutic targets. The current review summarizes (preclinical studies that demonstrate essential molecules involved in macrophage polarization that can be modulated and influence cardiac healing after AMI.

  14. Microcalcifications in atherosclerotic lesion of apolipoprotein E-deficient mouse

    Science.gov (United States)

    Debernardi, Nicola; Roijers, Ruben B; Krams, Rob; de Crom, Rini; Mutsaers, Peter HA; van der Vusse, Ger J

    2010-01-01

    Evidence is accumulating that calcium-rich microdeposits in the vascular wall might play a crucial role in the onset and progression of atherosclerosis. Here we investigated an atherosclerotic lesion of the carotid artery in an established murine model, i.e. the apolipoprotein E-deficient (APOE−/−) mouse to identify (i) the presence of microcalcifications, if any, (ii) the elemental composition of microcalcifications with special reference to calcium/phosphorus mass ratio and (iii) co-localization of increased concentrations of iron and zinc with microcalcifications. Atherosclerosis was induced by a flow-divider placed around the carotid artery resulting in low and high shear-stress regions. Element composition was assessed with a proton microprobe. Microcalcifications, predominantly present in the thickened intima of the low shear-stress region, were surrounded by areas with normal calcium levels, indicating that calcium-precipitation is a local event. The diameter of intimal microcalcifications varied from 6 to 70 μm. Calcium/phosphorus ratios of microcalcifications varied from 0.3 to 4.8, mainly corresponding to the ratio of amorphous calcium-phosphate. Increased iron and zinc concentrations commonly co-localized with microcalcifications. Our findings indicate that the atherosclerotic process in the murine carotid artery is associated with locally accumulated calcium, iron and zinc. The calcium-rich deposits resemble amorphous calcium phosphate rather than pure hydroxyapatite. We propose that the APOE−/− mouse, in which atherosclerosis was evoked by a flow-divider, offers a useful model to investigate the pathophysiological significance of accumulation of elements such as calcium, iron and zinc. PMID:20804542

  15. 自体骨髓内皮祖细胞移植治疗动脉粥样硬化大鼠急性脑缺血的实验研究%Treatment of acute cerebral ischemia in atherosclerotic rats with autologous transplantation with bone marrow-derived endothelial progenitor cells

    Institute of Scientific and Technical Information of China (English)

    朱江; 刘煜敏; 孔朝红; 道文欣

    2010-01-01

    Objective To explore the effeteness of autologous transplantation of bone marrow-derived endothelial progenitor cells in promoting the neovascularization and improving the neurological functional recovery in atherosclerotic rats with acute cerebral infarction. Methods Male Sprague-Dawley rat models of atherosclerosis were established by fat-rich diet feeding. Endothelial progenitor cells (EPCs) were obtained from bone marrow of all rats; the cells were cultured in vitro in Ml99 with VEGF, bFGF and EGF in it Assays were used to detect the expression of FLK-1 and CD34. on the 7th d, middle cerebral artery occlusion (MCAO) rat models were established by the method of thread thrombus. Three h after MCAO, all of the animals were randomized into experimental group (the autologous endothelial progenitor cells labeled with BrdU were injected into the carotid vein) and control group (same volume of PBS were injected into the carotid vein). Behavioral tests (modified neurological severity scale, mNSS) were performed 6 h and 1, 3, 7, 10 and 14 d after MCAO. Besides, immunohistochemical examinations were employed to observe the distribution of EPCs (labeled by BrdU) in the brain tissue and to measure the microvessel density. Results EPCs from bone marrow were isolated, induced and cultured successfully in vitro, which positively stained for FLK-1 by immunocytochemistry and partly positively expressed CD34 by immunofluorescence. The cells of FITC labeled UEA adsorption and DiL-acLDL internalization were positive under fluorescence confocal microscopy. These cells possessed robust proliferative potential and their number reached 5×106. On the 14th d, the neurological function recovery in the experimental group (mNSS scores: 6.13±0.30) was significantly improved as compared with that in the control group (mNSS scores: 8.50±0.46, P<0.05). On the 28th, some positive EPCs stained by BrdU were found in the experimental group and the numbers of blood vessels in the experimental

  16. Cold atmospheric plasma (CAP changes gene expression of key molecules of the wound healing machinery and improves wound healing in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Stephanie Arndt

    Full Text Available Cold atmospheric plasma (CAP has the potential to interact with tissue or cells leading to fast, painless and efficient disinfection and furthermore has positive effects on wound healing and tissue regeneration. For clinical implementation it is necessary to examine how CAP improves wound healing and which molecular changes occur after the CAP treatment. In the present study we used the second generation MicroPlaSter ß® in analogy to the current clinical standard (2 min treatment time in order to determine molecular changes induced by CAP using in vitro cell culture studies with human fibroblasts and an in vivo mouse skin wound healing model. Our in vitro analysis revealed that the CAP treatment induces the expression of important key genes crucial for the wound healing response like IL-6, IL-8, MCP-1, TGF-ß1, TGF-ß2, and promotes the production of collagen type I and alpha-SMA. Scratch wound healing assays showed improved cell migration, whereas cell proliferation analyzed by XTT method, and the apoptotic machinery analyzed by protein array technology, was not altered by CAP in dermal fibroblasts. An in vivo wound healing model confirmed that the CAP treatment affects above mentioned genes involved in wound healing, tissue injury and repair. Additionally, we observed that the CAP treatment improves wound healing in mice, no relevant side effects were detected. We suggest that improved wound healing might be due to the activation of a specified panel of cytokines and growth factors by CAP. In summary, our in vitro human and in vivo animal data suggest that the 2 min treatment with the MicroPlaSter ß® is an effective technique for activating wound healing relevant molecules in dermal fibroblasts leading to improved wound healing, whereas the mechanisms which contribute to these observed effects have to be further investigated.

  17. Cold atmospheric plasma (CAP) changes gene expression of key molecules of the wound healing machinery and improves wound healing in vitro and in vivo.

    Science.gov (United States)

    Arndt, Stephanie; Unger, Petra; Wacker, Eva; Shimizu, Tetsuji; Heinlin, Julia; Li, Yang-Fang; Thomas, Hubertus M; Morfill, Gregor E; Zimmermann, Julia L; Bosserhoff, Anja-Katrin; Karrer, Sigrid

    2013-01-01

    Cold atmospheric plasma (CAP) has the potential to interact with tissue or cells leading to fast, painless and efficient disinfection and furthermore has positive effects on wound healing and tissue regeneration. For clinical implementation it is necessary to examine how CAP improves wound healing and which molecular changes occur after the CAP treatment. In the present study we used the second generation MicroPlaSter ß® in analogy to the current clinical standard (2 min treatment time) in order to determine molecular changes induced by CAP using in vitro cell culture studies with human fibroblasts and an in vivo mouse skin wound healing model. Our in vitro analysis revealed that the CAP treatment induces the expression of important key genes crucial for the wound healing response like IL-6, IL-8, MCP-1, TGF-ß1, TGF-ß2, and promotes the production of collagen type I and alpha-SMA. Scratch wound healing assays showed improved cell migration, whereas cell proliferation analyzed by XTT method, and the apoptotic machinery analyzed by protein array technology, was not altered by CAP in dermal fibroblasts. An in vivo wound healing model confirmed that the CAP treatment affects above mentioned genes involved in wound healing, tissue injury and repair. Additionally, we observed that the CAP treatment improves wound healing in mice, no relevant side effects were detected. We suggest that improved wound healing might be due to the activation of a specified panel of cytokines and growth factors by CAP. In summary, our in vitro human and in vivo animal data suggest that the 2 min treatment with the MicroPlaSter ß® is an effective technique for activating wound healing relevant molecules in dermal fibroblasts leading to improved wound healing, whereas the mechanisms which contribute to these observed effects have to be further investigated.

  18. Atherosclerotic Aneurysm of the Basilar Artery and Hydrocephalus. A Case Report

    Directory of Open Access Journals (Sweden)

    Ania Alvarado Borges

    2014-08-01

    Full Text Available Intracranial aneurysms are fairly common. Many of them produce no symptoms, often remaining undiagnosed during life. At autopsy, aneurysms of the basilar artery appear in 2 to 5% of the cases; among them, saccular and congenital aneurysms are more common than atherosclerotic and fusiform aneurysms. A case of atherosclerotic aneurysm of the basilar artery diagnosed at autopsy in an 88-year-old man is presented. This patient had been admitted with a diagnosis of ischemic stroke, intracranial hypertension and hydrocephalus, which led physicians to consider a posterior fossa tumor. This paper aims at presenting the autopsy findings that showed the presence of an atherosclerotic aneurysm of the basilar artery.

  19. Scar-free cutaneous wound healing in the leopard gecko, Eublepharis macularius.

    Science.gov (United States)

    Peacock, Hanna M; Gilbert, Emily A B; Vickaryous, Matthew K

    2015-11-01

    Cutaneous wounds heal with two possible outcomes: scarification or near-perfect integumentary restoration. Whereas scar formation has been intensively investigated, less is known about the tissue-level events characterising wounds that spontaneously heal scar-free, particularly in non-foetal amniotes. Here, a spatiotemporal investigation of scar-free cutaneous wound healing following full-thickness excisional biopsies to the tail and body of leopard geckos (Eublepharis macularius) is provided. All injuries healed without scarring. Cutaneous repair involves the development of a cell-rich aggregate within the wound bed, similar to scarring wounds. Unlike scar formation, scar-free healing involves a more rapid closure of the wound epithelium, and a delay in blood vessel development and collagen deposition within the wound bed. It was found that, while granulation tissue of scarring wounds is hypervascular, scar-free wound healing conspicuously does not involve a period of exuberant blood vessel formation. In addition, during scar-free wound healing the newly formed blood vessels are typically perivascular cell-supported. Immunohistochemistry revealed widespread expression of both the pro-angiogenic factor vascular endothelial growth factor A and the anti-angiogenic factor thrombospondin-1 within the healing wound. It was found that scar-free wound healing is an intrinsic property of leopard gecko integument, and involves a modulation of the cutaneous scar repair program. This proportional revascularisation is an important factor in scar-free wound healing.

  20. Activation of sterol regulatory element binding protein and NLRP3 inflammasome in atherosclerotic lesion development in diabetic pigs.

    Directory of Open Access Journals (Sweden)

    Yu Li

    Full Text Available BACKGROUND: Aberrantly elevated sterol regulatory element binding protein (SREBP, the lipogenic transcription factor, contributes to the development of fatty liver and insulin resistance in animals. Our recent studies have discovered that AMP-activated protein kinase (AMPK phosphorylates SREBP at Ser-327 and inhibits its activity, represses SREBP-dependent lipogenesis, and thereby ameliorates hepatic steatosis and atherosclerosis in insulin-resistant LDLR(-/- mice. Chronic inflammation and activation of NLRP3 inflammasome have been implicated in atherosclerosis and fatty liver disease. However, whether SREBP is involved in vascular lipid accumulation and inflammation in atherosclerosis remains largely unknown. PRINCIPAL FINDINGS: The preclinical study with aortic pouch biopsy specimens from humans with atherosclerosis and diabetes shows intense immunostaining for SREBP-1 and the inflammatory marker VCAM-1 in atherosclerotic plaques. The cleavage processing of SREBP-1 and -2 and expression of their target genes are increased in the well-established porcine model of diabetes and atherosclerosis, which develops human-like, complex atherosclerotic plaques. Immunostaining analysis indicates an elevation in SREBP-1 that is primarily localized in endothelial cells and in infiltrated macrophages within fatty streaks, fibrous caps with necrotic cores, and cholesterol crystals in advanced lesions. Moreover, concomitant suppression of NAD-dependent deacetylase SIRT1 and AMPK is observed in atherosclerotic pigs, which leads to the proteolytic activation of SREBP-1 by diminishing the deacetylation and Ser-372 phosphorylation of SREBP-1. Aberrantly elevated NLRP3 inflammasome markers are evidenced by increased expression of inflammasome components including NLPR3, ASC, and IL-1β. The increase in SREBP-1 activity and IL-1β production in lesions is associated with vascular inflammation and endothelial dysfunction in atherosclerotic pig aorta, as demonstrated

  1. Self-healing epoxy composites: preparation, characterization and healing performance

    OpenAIRE

    Reaz A. Chowdhury; Mahesh V. Hosur; Md. Nuruddin; Alfred Tcherbi-Narteh; Ashok Kumar; Veera Boddu; Shaik Jeelani

    2015-01-01

    Low velocity impact damage is common in fiber reinforced composites, which leads to micro-crack and interfacial debonding, where damage is microscopic and invisible. The concept of self-healing composites can be a way of overcoming this limitation and extending the life expectancy while expanding their usage in structural applications. In the current study, extrinsic self-healing concept was adopted using urea-formaldehyde microcapsules containing room temperature curing epoxy resin system (S...

  2. The Role of Matrix Metalloproteinases in Diabetic Wound Healing in relation to Photobiomodulation

    OpenAIRE

    Sandra Matabi Ayuk; Heidi Abrahamse; Nicolette Nadene Houreld

    2016-01-01

    The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs) play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM) during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wound...

  3. Cellular and molecular mechanisms of repair in acute and chronic wound healing

    OpenAIRE

    Martin, P.; Nunan, R

    2015-01-01

    Summary A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to ...

  4. Mucopolysaccharides from psyllium involved in wound healing.

    Science.gov (United States)

    Westerhof, W; Das, P K; Middelkoop, E; Verschoor, J; Storey, L; Regnier, C

    2001-01-01

    Mucopolysaccharides derived from the husk of psyllium (Plantago ovata) have properties beneficial for wound cleansing and wound healing. Recent studies indicate that these mucopolysaccharides also limit scar formation. Our in vitro and in vivo studies aimed to investigate the mechanisms involved, e.g., fluid absorption, bacterial adherence and in vitro stimulatory effects on macrophages, which are pivotal in wound healing. The mucopolysaccharides contained in a sachet (Askina Cavity) or in a hydrocolloid mixture (Askina Hydro) were found to have a gradual and sustained absorbency over a period of 7 days, amounting to 4-6 times their weight in water. The swelling index was 9 mm after 312 h. Adherence of wound bacteria to the mucopolysaccharides started after 2 h and was more pronounced after 3 h. Semiquantitative measurements of bacterial adherence used centrifugation and subsequent optical density determinations of supernatant. These confirmed the strong adherence potential of psyllium particles. Lactic acid dehydrogenase staining of pretreated cultured human skin explants did not reveal toxicity of the mucopolysaccharides derived from psyllium husk. Langerhans' cell migration from the epidermis was negligible and interleukin-1 beta expression in the explants was not significant, supporting the very low allergenic potential of psyllium. The characteristics of mucopolysaccharide granulate derived from psyllium husk in Askina Cavity and Askina Hydro related to fluid absorption, bacterial adherence, biocompatibility, stimulation of macrophages, irritancy response and allergenicity showed an optimal profile, supporting the good clinical performance of wound healing products containing psyllium husk. PMID:11951574

  5. P2Y6 receptor potentiates pro-inflammatory responses in macrophages and exhibits differential roles in atherosclerotic lesion development.

    Directory of Open Access Journals (Sweden)

    Ricardo A Garcia

    Full Text Available BACKGROUND: P2Y(6, a purinergic receptor for UDP, is enriched in atherosclerotic lesions and is implicated in pro-inflammatory responses of key vascular cell types and macrophages. Evidence for its involvement in atherogenesis, however, has been lacking. Here we use cell-based studies and three murine models of atherogenesis to evaluate the impact of P2Y(6 deficiency on atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Cell-based studies in 1321N1 astrocytoma cells, which lack functional P2Y(6 receptors, showed that exogenous expression of P2Y(6 induces a robust, receptor- and agonist-dependent secretion of inflammatory mediators IL-8, IL-6, MCP-1 and GRO1. P2Y(6-mediated inflammatory responses were also observed, albeit to a lesser extent, in macrophages endogenously expressing P2Y(6 and in acute peritonitis models of inflammation. To evaluate the role of P2Y(6 in atherosclerotic lesion development, we used P2Y(6-deficient mice in three mouse models of atherosclerosis. A 43% reduction in aortic arch plaque was observed in high fat-fed LDLR knockout mice lacking P2Y(6 receptors in bone marrow-derived cells. In contrast, no effect on lesion development was observed in fat-fed whole body P2Y(6xLDLR double knockout mice. Interestingly, in a model of enhanced vascular inflammation using angiotensin II, P2Y(6 deficiency enhanced formation of aneurysms and exhibited a trend towards increased atherosclerosis in the aorta of LDLR knockout mice. CONCLUSIONS: P2Y(6 receptor augments pro-inflammatory responses in macrophages and exhibits a pro-atherogenic role in hematopoietic cells. However, the overall impact of whole body P2Y(6 deficiency on atherosclerosis appears to be modest and could reflect additional roles of P2Y(6 in vascular disease pathophysiologies, such as aneurysm formation.

  6. Serum Asymmetric Dimethylarginine, and Adiponectin as Predictors of Atherosclerotic Risk among Obese Egyptian Children

    Directory of Open Access Journals (Sweden)

    Enas R. Abdel Hameed

    2014-06-01

    CONCLUSIONS: Our results revealed that ADMA, Adiponectin and lipid profile can be considered as predictive biomarkers in prediction and prevention of atherosclerotic risk in the future among overweight and obese Egyptian children.

  7. A focus on inflammation as a major risk factor for atherosclerotic cardiovascular diseases.

    Science.gov (United States)

    Gregersen, Ida; Holm, Sverre; Dahl, Tuva B; Halvorsen, Bente; Aukrust, Pål

    2016-01-01

    Atherosclerosis is a dynamic, pathogenic process in the artery wall, with potential adverse outcome for the host. Acute events such as myocardial infarction and ischemic stroke often result from rupture of unstable atherosclerotic lesions. Understanding the underlying pathology of such lesions and why and when they rupture, is therefore of great interest for the development of new diagnostics and treatment. Inflammation is one of the key drivers of atherosclerotic plaque development and the interplay between inflammation and lipids constitutes the hallmark of atherosclerotic disease. This review summarizes the role of inflammation in atherosclerosis and presents some of the latest discoveries as well as unmet needs regarding the role of inflammation as major risk factor in atherosclerotic disease.

  8. Morphological study of atherosclerotic plaque and its application in vulnerability evaluation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The relationships between the morphological characteristics and the vulnerability of atherosclerotic plaque were analyzed theoretically and several suggestions were proposed to evaluate the plaque vulnerability. Validated by animal experiments and clinical studies, the theoretical results were confirmed.

  9. El trasplante autólogo de células mesoteliales como acelerador y modificador de la cicatrización cutánea en ratas Autologous mesothelial cells transplantation as accelerator and skin healing modifier in rats

    Directory of Open Access Journals (Sweden)

    R. Esparza Iturbide

    2013-03-01

    ó menor inflamación y fibrosis, mayor colágeno y datos compatibles con una fase de remodelación. En conclusión, el autotrasplante de células mesoteliales peritoneales en heridas de espesor total acelera el proceso de cicatrización cutánea normal en ratas ya que disminuye la inflamación, la fibrosis y aumenta el colágeno.The purpose of this study was to verify if the autologous peritoneal mesothelial cells in full thickness wounds on rats, speed up and adjust the normal skin healing process. Based on the theory that mesothelial cells from tissues such as peritoneum, pleura or pericardium, are responsible for one of the faster healing process and synthesize stimulating wound healing and chemotactical factors (hence the genesis of surgical adhesions, besides possessing the ability to differentiate into other cell series (plasticity. We designed a pilot, analytical, longitudinal, prospective and comparative study in the Laboratory of Experimental Surgery at The American British Cowdray Medical Center, Mexico City (México. Were used 15 Wistar rats which were divided into 2 groups: Group I (n = 5 where after general anesthesia, skin removed 3 mm in diameter with microsurgical technique in the back and was close by secondary intention; and Group II or experimental group (n = 10 where laparotomy was performed with excision of the parietal peritoneum and primary closure, excision of full thickness skin on the dorsal surface of 3mm diameter and peritoneal autograft placement on the dorsal wound. In histological analysis, were reviewed 6 variables: collagen, fibroblasts, number of vessels, macrophages, inflammatory cells and retraction, to point out fully the nature and characteristics of healing in both groups. For the statistical analysis we used Statistical Package for Social Sciences 17.0. The descriptive statistics was made using frequency measures of central tendency and dispersion. The results showed that the Group I rats, had increased inflammation, fibrosis and

  10. A Novel Three-Dimensional Wound Healing Model

    Directory of Open Access Journals (Sweden)

    Zhuo J. Chen

    2014-12-01

    Full Text Available Wound healing is a well-orchestrated process, with various cells and growth factors coming into the wound bed at a specific time to influence the healing. Understanding the wound healing process is essential to generating wound healing products that help with hard-to-heal acute wounds and chronic wounds. The 2D scratch assay whereby a wound is created by scratching a confluent layer of cells on a 2D substrate is well established and used extensively but it has a major limitation—it lacks the complexity of the 3D wound healing environment. Established 3D wound healing models also have many limitations. In this paper, we present a novel 3D wound healing model that closely mimics the skin wound environment to study the cell migration of fibroblasts and keratinocytes. Three major components that exist in the wound environment are introduced in this new model: collagen, fibrin, and human foreskin fibroblasts. The novel 3D model consists of a defect, representing the actual wound, created by using a biopsy punch in a 3D collagen construct. The defect is then filled with collagen or with various solutions of fibrinogen and thrombin that polymerize into a 3D fibrin clot. Fibroblasts are then added on top of the collagen and their migration into the fibrin—or collagen—filled defect is followed for nine days. Our data clearly shows that fibroblasts migrate on both collagen and fibrin defects, though slightly faster on collagen defects than on fibrin defects. This paper shows the visibility of the model by introducing a defect filled with fibrin in a 3D collagen construct, thus mimicking a wound. Ongoing work examines keratinocyte migration on the defects of a 3D construct, which consists of collagen-containing fibroblasts. The model is also used to determine the effects of various growth factors, delivered in the wound defects, on fibroblasts’ and keratinocytes’ migration into the defects. Thus this novel 3D wound healing model provides a more

  11. Fibroblast-specific upregulation of Flightless I impairs wound healing.

    Science.gov (United States)

    Turner, Christopher T; Waters, James M; Jackson, Jessica E; Arkell, Ruth M; Cowin, Allison J

    2015-09-01

    The cytoskeletal protein Flightless (Flii) is a negative regulator of wound healing. Upregulation of Flii is associated with impaired migration, proliferation and adhesion of both fibroblasts and keratinocytes. Importantly, Flii translocates from the cytoplasm to the nucleus in response to wounding in fibroblasts but not keratinocytes. This cell-specific nuclear translocation of Flii suggests that Flii may directly regulate gene expression in fibroblasts, providing one potential mechanism of action for Flii in the wound healing response. To determine whether the tissue-specific upregulation of Flii in fibroblasts was important for the observed inhibitory effects of Flii on wound healing, an inducible fibroblast-specific Flii overexpressing mouse model was generated. The inducible ROSA26 system allowed the overexpression of Flii in a temporal and tissue-specific manner in response to tamoxifen treatment. Wound healing in the inducible mice was impaired, with wounds at day 7 postwounding significantly larger than those from non-inducible controls. There was also reduced collagen maturation, increased myofibroblast infiltration and elevated inflammation. The impaired healing response was similar in magnitude to that observed in mice with non-tissue-specific upregulation of Flii suggesting that fibroblast-derived Flii may have an important role in the wound healing response.

  12. Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin.

    Directory of Open Access Journals (Sweden)

    Theofilos Poutahidis

    Full Text Available Wound healing capability is inextricably linked with diverse aspects of physical fitness ranging from recovery after minor injuries and surgery to diabetes and some types of cancer. Impact of the microbiome upon the mammalian wound healing process is poorly understood. We discover that supplementing the gut microbiome with lactic acid microbes in drinking water accelerates the wound-healing process to occur in half the time required for matched control animals. Further, we find that Lactobacillus reuteri enhances wound-healing properties through up-regulation of the neuropeptide hormone oxytocin, a factor integral in social bonding and reproduction, by a vagus nerve-mediated pathway. Bacteria-triggered oxytocin serves to activate host CD4+Foxp3+CD25+ immune T regulatory cells conveying transplantable wound healing capacity to naive Rag2-deficient animals. This study determined oxytocin to be a novel component of a multi-directional gut microbe-brain-immune axis, with wound-healing capability as a previously unrecognized output of this axis. We also provide experimental evidence to support long-standing medical traditions associating diet, social practices, and the immune system with efficient recovery after injury, sustained good health, and longevity.

  13. THE BIOLOGY OF FRACTURE HEALING

    OpenAIRE

    Marsell, Richard; Einhorn, Thomas A.

    2011-01-01

    The biology of fracture healing is a complex biological process that follows specific regenerative patterns and involves changes in the expression of several thousand genes. Although there is still much to be learned to fully comprehend the pathways of bone regeneration, the over-all pathways of both the anatomical and biochemical events have been thoroughly investigated. These efforts have provided a general understanding of how fracture healing occurs. Following the initial trauma, bone hea...

  14. Modeling self-healing materials

    OpenAIRE

    Balazs, Anna C

    2007-01-01

    We describe recent computational studies to design such systems as ‘artificial leukocytes’ that facilitate the healing of damaged substrates, polymer nanocomposites where nanoparticles are driven to fill cracks in fractured surfaces, and polymer gels that effectively act as a ‘skin’ by signaling mechanical impact. Computational research into self-healing materials is still in its infancy. However, progress in this field can ultimately facilitate the fabrication of the next generation of adapt...

  15. Self-Healing Wire Insulation

    Science.gov (United States)

    Parrish, Clyde F. (Inventor)

    2012-01-01

    A self-healing system for an insulation material initiates a self-repair process by rupturing a plurality of microcapsules disposed on the insulation material. When the plurality of microcapsules are ruptured, reactants within the plurality of microcapsules react to form a replacement polymer in a break of the insulation material. This self-healing system has the ability to repair multiple breaks in a length of insulation material without exhausting the repair properties of the material.

  16. The role of neuropeptide Y in the pathophysiology of atherosclerotic cardiovascular disease.

    Science.gov (United States)

    Zhu, Ping; Sun, Weiwei; Zhang, Chenliang; Song, Zhiyuan; Lin, Shu

    2016-10-01

    With average life expectancy rising greatly, the incidence rate of arteriosclerotic cardiovascular disease (ASCVD) has significantly increased. The heart disease has now become the number one killer that threatens the global population health, the second is stroke. It will be of great significance to investigate the underlying pathophysiological mechanisms of ASCVD in order to promote effective prevention and treatment. The neuropeptide Y (NPY) has now been discovered for more than thirty years and is widely distributed in the central nervous system (CNS) and peripheral tissues. By combining with certain receptors, NPY performs a variety of physiological functions, including the regulation of food intake, cardiovascular effects, development, hormonal secretion, sexual behavior, biological rhythms, temperature and emotion. In ASCVD, increased peripheral NPY was involved in the pathophysiological process of atherosclerosis through affecting the vascular endothelial dysfunction, the formation of foam cells, the proliferation of vascular smooth muscle cells, the local inflammatory response of plaques and the activation and aggregation of platelets. Via central and/or the peripheral nervous system, increased NPY was associated with dyslipidemia, hypertension, obesity, diabetes, impaired glucose tolerance, and smoking which are all risk factors for ASCVD. In this review, we summarize the role of neuropeptide Y in the development of atherosclerotic cardiovascular disease. PMID:27389447

  17. Human macrophage scavenger receptors: Primary structure, expression, and localization in atherosclerotic lesions

    International Nuclear Information System (INIS)

    Two types of cDNAs for human macrophage scavenger receptors were cloned from a cDNA library derived from the phorbol ester-treated human monocytic cell line THP-1. The type I and type II human scavenger receptors encoded by these cDNAs are homologous (73% and 71% amino acid identity) to their previously characterized bovine counterparts and consist of six domains: cytoplasmic (I), membrane-spanning (II), spacer (III), α-helical coiled-coil (IV), collagen-like (V), and a type-specific C-terminal (VI). The receptor gene is located on human chromosome 8. The human receptors expressed in CHO-K1 cells mediated endocytosis of modified low density lipoproteins. Two mRNAs, 4.0 and 3.2 kilobases, have been detected in human liver, placenta, and brain. Immunohistochemical studies using an anti-peptide antibody which recognizes human scavenger receptors indicated the presence of the scavenger receptors in the macrophages of lipid-rich atherosclerotic lesions, suggesting the involvement of scavenger receptors in atherogenesis

  18. Symptomatic intracranial vertebral artery atherosclerotic stenosis (≥70%) with concurrent contralateral vertebral atherosclerotic diseases in 88 patients treated with the intracranial stenting

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zi-Liang [Stroke Center, Henan Provincial People’s Hospital, Zhengzhou University (China); Gao, Bu-Lang [Department of Medical Research Shijiazhuang First Hospital, Hebei Medical University (China); Li, Tian-Xiao, E-mail: litianxiaod@163.com [Stroke Center, Henan Provincial People’s Hospital, Zhengzhou University (China); Cai, Dong-Yang; Zhu, Liang-Fu; Bai, Wei-Xing; Xue, Jiang-Yu; Li, Zhao-Shuo [Stroke Center, Henan Provincial People’s Hospital, Zhengzhou University (China)

    2015-09-15

    Highlights: • Symptomatic vertebral artery stenosis can be treated with intracranial stenting. • Stenting for intracranial vertebral artery stenosis is safe and effective. • Stenting for intracranial vertebral artery stenosis can prevent long-term stroke. - Abstract: Purpose: To investigate the safety, effect and instent restenosis rate of Wingspan stenting in treating patients with intracranial vertebral artery atherosclerotic stenosis (70–99%) concurrent with contralateral vertebral artery atherosclerotic diseases. Materials and methods: Eighty-eight patients with severe symptomatic intracranial vertebral artery atherosclerotic stenosis (≥70%) combined with contralateral vertebral artery atherosclerotic diseases were treated with the Wingpsan stent. All the baseline, cerebral angiography, success rate, perioperative complications, clinical and imaging follow-up data were prospectively analyzed. Results: The success rate of stenting was 100%, and the mean stenotic rate was reduced from prestenting (84.9 ± 6.8)% to poststenting (17.2 ± 5.9)%. The perioperative stroke rate was 1.1%. Among eighty patients (90.9%) with clinical follow-up 8-62 months (mean 29.3 ± 17.2) poststenting, five (6.3%) had posterior circulation TIA only, three (3.8%) had mild stroke in the posterior circulation but recovered completely, and another five patients greater than 70 years old died of non-ischemic stroke. Imaging follow-up in 46 patients (52.3%) 5–54 months (mean 9.9 ± 9.9) following stenting revealed instent restenosis in 12 patients (26.1%) including 7 (58.3%) symptomatic restenosis. Age and residual stenosis were the two factors to significantly (P < 0.05) affect instent restenosis. Conclusion: Wingspan stenting in the intracranial vertebral artery atherosclerotic stenosis combined with contralateral vertebral artery atherosclerotic diseases has a low perioperative stroke rate and a good preventive effect on long-term ischemic stroke, but the instent restenosis

  19. Symptomatic intracranial vertebral artery atherosclerotic stenosis (≥70%) with concurrent contralateral vertebral atherosclerotic diseases in 88 patients treated with the intracranial stenting

    International Nuclear Information System (INIS)

    Highlights: • Symptomatic vertebral artery stenosis can be treated with intracranial stenting. • Stenting for intracranial vertebral artery stenosis is safe and effective. • Stenting for intracranial vertebral artery stenosis can prevent long-term stroke. - Abstract: Purpose: To investigate the safety, effect and instent restenosis rate of Wingspan stenting in treating patients with intracranial vertebral artery atherosclerotic stenosis (70–99%) concurrent with contralateral vertebral artery atherosclerotic diseases. Materials and methods: Eighty-eight patients with severe symptomatic intracranial vertebral artery atherosclerotic stenosis (≥70%) combined with contralateral vertebral artery atherosclerotic diseases were treated with the Wingpsan stent. All the baseline, cerebral angiography, success rate, perioperative complications, clinical and imaging follow-up data were prospectively analyzed. Results: The success rate of stenting was 100%, and the mean stenotic rate was reduced from prestenting (84.9 ± 6.8)% to poststenting (17.2 ± 5.9)%. The perioperative stroke rate was 1.1%. Among eighty patients (90.9%) with clinical follow-up 8-62 months (mean 29.3 ± 17.2) poststenting, five (6.3%) had posterior circulation TIA only, three (3.8%) had mild stroke in the posterior circulation but recovered completely, and another five patients greater than 70 years old died of non-ischemic stroke. Imaging follow-up in 46 patients (52.3%) 5–54 months (mean 9.9 ± 9.9) following stenting revealed instent restenosis in 12 patients (26.1%) including 7 (58.3%) symptomatic restenosis. Age and residual stenosis were the two factors to significantly (P < 0.05) affect instent restenosis. Conclusion: Wingspan stenting in the intracranial vertebral artery atherosclerotic stenosis combined with contralateral vertebral artery atherosclerotic diseases has a low perioperative stroke rate and a good preventive effect on long-term ischemic stroke, but the instent restenosis

  20. Moderate overweight is beneficial and severe obesity detrimental for patients with documented atherosclerotic heart disease

    DEFF Research Database (Denmark)

    Azimi, Aziza; Charlot, Mette Gitz; Torp-Pedersen, Christian;

    2013-01-01

    Obesity is paradoxically associated with enhanced survival in patients with established cardiovascular disease. We explored this paradox further by examining the influence of obesity on survival in patients with verified atherosclerotic heart disease.......Obesity is paradoxically associated with enhanced survival in patients with established cardiovascular disease. We explored this paradox further by examining the influence of obesity on survival in patients with verified atherosclerotic heart disease....

  1. Effects of Mechanical Properties and Atherosclerotic Artery Size on Biomechanical Plaque Disruption - Mouse versus Human

    OpenAIRE

    Riou, Laurent M.; Broisat, Alexis; Ghezzi, Catherine; Finet, Gérard; Rioufol, Gilles; Gharib, Ahmed M.; Pettigrew, Roderic I.; Ohayon, Jacques

    2014-01-01

    Mouse models of atherosclerosis are extensively being used to study the mechanisms of atherosclerotic plaque development and the results are frequently extrapolated to humans. However, major differences have been described between murine and human atherosclerotic lesions and the determination of similarities and differences between these species has been largely addressed recently. This study takes over and extends previous studies performed by our group and related to the biomechanical chara...

  2. Mucosal Administration of Collagen V Ameliorates the Atherosclerotic Plaque Burden by Inducing Interleukin 35-dependent Tolerance.

    Science.gov (United States)

    Park, Arick C; Huang, Guorui; Jankowska-Gan, Ewa; Massoudi, Dawiyat; Kernien, John F; Vignali, Dario A; Sullivan, Jeremy A; Wilkes, David S; Burlingham, William J; Greenspan, Daniel S

    2016-02-12

    We have shown previously that collagen V (col(V)) autoimmunity is a consistent feature of atherosclerosis in human coronary artery disease and in the Apoe(-/-) mouse model. We have also shown sensitization of Apoe(-/-) mice with col(V) to markedly increase the atherosclerotic burden, providing evidence of a causative role for col(V) autoimmunity in atherosclerotic pathogenesis. Here we sought to determine whether induction of immune tolerance to col(V) might ameliorate atherosclerosis, providing further evidence for a causal role for col(V) autoimmunity in atherogenesis and providing insights into the potential for immunomodulatory therapeutic interventions. Mucosal inoculation successfully induced immune tolerance to col(V) with an accompanying reduction in plaque burden in Ldlr(-/-) mice on a high-cholesterol diet. The results therefore demonstrate that inoculation with col(V) can successfully ameliorate the atherosclerotic burden, suggesting novel approaches for therapeutic interventions. Surprisingly, tolerance and reduced atherosclerotic burden were both dependent on the recently described IL-35 and not on IL-10, the immunosuppressive cytokine usually studied in the context of induced tolerance and amelioration of atherosclerotic symptoms. In addition to the above, using recombinant protein fragments, we were able to localize two epitopes of the α1(V) chain involved in col(V) autoimmunity in atherosclerotic Ldlr(-/-) mice, suggesting future courses of experimentation for the characterization of such epitopes.

  3. A Study on Evaluation of Apoptosis and Expression of Bcl-2-Related Marker in Wound Healing of Streptozotocin-Induced Diabetic Rats

    OpenAIRE

    Surya Bhan; Rahul Mitra; Arya, A. K.; Pandey, H. P.; Tripathi, K.

    2013-01-01

    Uncontrolled blood sugar is a major cause of vascular complications and delayed wound healing in diabetes mellitus. During wound healing process, normally, apoptosis is responsible for events such as removal of inflammatory cells and evolution of granulation tissue into scar which occur during the late phase of wound healing. Early apoptosis can lead to abnormal wound healing by removing granulation tissue including fibroblast, endothelial cell, and small vessels. To determine the role of apo...

  4. Fluid-phase pinocytosis of LDL by macrophages: a novel target to reduce macrophage cholesterol accumulation in atherosclerotic lesions.

    Science.gov (United States)

    Kruth, Howar S

    2013-01-01

    Circulating low-density lipoprotein (LDL) that enters the blood vessel wall is the main source of cholesterol that accumulates within atherosclerotic plaques. Much of the deposited cholesterol accumulates within plaque macrophages converting these macrophages into cholesterol-rich foamy looking cells. Cholesterol accumulation in macrophages contributes to cholesterol retention within the vessel wall, and promotes vessel wall inflammation and thrombogenicity. Thus, how macrophages accumulate cholesterol and become foam cells has been the subject of intense investigation. It is generally believed that macrophages accumulate cholesterol only through scavenger receptor-mediated uptake of modified LDL. However, an alternative mechanism for macrophage foam cell formation that does not depend on LDL modification or macrophage receptors has been elucidated. By this alternative mechanism, macrophages show receptor-independent uptake of unmodified native LDL that is mediated by fluid-phase pinocytosis. In receptor-independent, fluid-phase pinocytosis, macrophages take up LDL as part of the fluid that they ingest during micropinocytosis within small vesicles called micropinosomes, and by macropinocytosis within larger vacuoles called macropinosomes. This produces cholesterol accumulation in macrophages to levels characteristic of macrophage foam cells in atherosclerotic plaques. Fluid-phase pinocytosis of LDL is a plausible mechanism that can explain how macrophages accumulate cholesterol and become disease-causing foam cells. Fluid-phase pinocytosis of LDL is a relevant pathway to target for modulating macrophage cholesterol accumulation in atherosclerosis. Recent studies show that phosphoinositide 3-kinase (PI3K), liver X receptors (LXRs), the macrophage colony-stimulating factor (M-CSF) receptor, and protein kinase C (PKC) mediate macrophage macropinocytosis of LDL, and thus, these may be relevant targets to inhibit macrophage cholesterol accumulation in atherosclerosis

  5. Putting on the brakes: Bacterial impediment of wound healing.

    Science.gov (United States)

    Brothers, Kimberly M; Stella, Nicholas A; Hunt, Kristin M; Romanowski, Eric G; Liu, Xinyu; Klarlund, Jes K; Shanks, Robert M Q

    2015-01-01

    The epithelium provides a crucial barrier to infection, and its integrity requires efficient wound healing. Bacterial cells and secretomes from a subset of tested species of bacteria inhibited human and porcine corneal epithelial cell migration in vitro and ex vivo. Secretomes from 95% of Serratia marcescens, 71% of Pseudomonas aeruginosa, 29% of Staphylococcus aureus strains, and other bacterial species inhibited epithelial cell migration. Migration of human foreskin fibroblasts was also inhibited by S. marcescens secretomes indicating that the effect is not cornea specific. Transposon mutagenesis implicated lipopolysaccharide (LPS) core biosynthetic genes as being required to inhibit corneal epithelial cell migration. LPS depletion of S. marcescens secretomes with polymyxin B agarose rendered secretomes unable to inhibit epithelial cell migration. Purified LPS from S. marcescens, but not from Escherichia coli or S. marcescens strains with mutations in the waaG and waaC genes, inhibited epithelial cell migration in vitro and wound healing ex vivo. Together these data suggest that S. marcescens LPS is sufficient for inhibition of epithelial wound healing. This study presents a novel host-pathogen interaction with implications for infections where bacteria impact wound healing and provides evidence that secreted LPS is a key factor in the inhibitory mechanism.

  6. Maintenance of Macrophage Redox Status by ChREBP Limits Inflammation and Apoptosis and Protects against Advanced Atherosclerotic Lesion Formation

    Directory of Open Access Journals (Sweden)

    Vincent Sarrazy

    2015-10-01

    Full Text Available Enhanced glucose utilization can be visualized in atherosclerotic lesions and may reflect a high glycolytic rate in lesional macrophages, but its causative role in plaque progression remains unclear. We observe that the activity of the carbohydrate-responsive element binding protein ChREBP is rapidly downregulated upon TLR4 activation in macrophages. ChREBP inactivation refocuses cellular metabolism to a high redox state favoring enhanced inflammatory responses after TLR4 activation and increased cell death after TLR4 activation or oxidized LDL loading. Targeted deletion of ChREBP in bone marrow cells resulted in accelerated atherosclerosis progression in Ldlr−/− mice with increased monocytosis, lesional macrophage accumulation, and plaque necrosis. Thus, ChREBP-dependent macrophage metabolic reprogramming hinders plaque progression and establishes a causative role for leukocyte glucose metabolism in atherosclerosis.

  7. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models.

    Science.gov (United States)

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE(-/-) and ApoE(-/-)Fbn1C1039G(+/-) mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  8. Colesevelam hydrochloride: reducing atherosclerotic coronary heart disease risk factors

    Directory of Open Access Journals (Sweden)

    Harold Bays

    2007-11-01

    Full Text Available Harold Bays1, Peter H Jones21L-MARC Research Center, Louisville KY, USA; 2Baylor College of Medicine, Houston, TX, USAAbstract: Colesevelam HCl is a bile acid sequestrant (BAS which has been specifically designed with a unique structure for the purpose of improving tolerability and reducing potential drug interactions compared to older BAS, such as cholestyramine and colestipol. As a class, BAS are known to reduce cholesterol and glucose levels, and to reduce atherosclerotic coronary heart disease (CHD risk as monotherapy, and in combination with other lipid-altering drug therapies. Colesevelam HCl has specifically been shown to reduce total and low-density lipoprotein (LDL cholesterol levels, and has been approved as a cholesterol-lowering drug since year 2000. It has also been shown to reduce glucose levels. This discussion reviews mechanisms by which BAS lower cholesterol, and potential mechanisms by which BAS lower glucose levels in patients with type 2 diabetes mellitus. Finally this paper specifically reviews colesevelam HCl’s pharmacology, lipid and glucose efficacy, safety/tolerability, and clinical use.Keywords: cholesterol, colesevelam HCl, coronary heart disease, diabetes mellitus, glucose, lipids

  9. Directional spatial frequency analysis of lipid distribution in atherosclerotic plaque

    Science.gov (United States)

    Korn, Clyde; Reese, Eric; Shi, Lingyan; Alfano, Robert; Russell, Stewart

    2016-04-01

    Atherosclerosis is characterized by the growth of fibrous plaques due to the retention of cholesterol and lipids within the artery wall, which can lead to vessel occlusion and cardiac events. One way to evaluate arterial disease is to quantify the amount of lipid present in these plaques, since a higher disease burden is characterized by a higher concentration of lipid. Although therapeutic stimulation of reverse cholesterol transport to reduce cholesterol deposits in plaque has not produced significant results, this may be due to current image analysis methods which use averaging techniques to calculate the total amount of lipid in the plaque without regard to spatial distribution, thereby discarding information that may have significance in marking response to therapy. Here we use Directional Fourier Spatial Frequency (DFSF) analysis to generate a characteristic spatial frequency spectrum for atherosclerotic plaques from C57 Black 6 mice both treated and untreated with a cholesterol scavenging nanoparticle. We then use the Cauchy product of these spectra to classify the images with a support vector machine (SVM). Our results indicate that treated plaque can be distinguished from untreated plaque using this method, where no difference is seen using the spatial averaging method. This work has the potential to increase the effectiveness of current in-vivo methods of plaque detection that also use averaging methods, such as laser speckle imaging and Raman spectroscopy.

  10. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

    Science.gov (United States)

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  11. Imaging of atherosclerotic plaques by optical coherence tomography (OCT)

    Science.gov (United States)

    Perree, Jop; van Leeuwen, Ton G. J. M.; Pasterkamp, Gerard; Izatt, Joseph A.

    2000-05-01

    Optical Coherence Tomography (OCT) is an imaging technique that measures the intensity of light back scattered from sub- surface tissue structures with a very high resolution. This report describes the qualitative and quantitative correlation of OCT and histology measurements for plaque presence and thickness of caps overlying atherosclerotic plaques, respectively. Imaging of samples (n equals 12) was performed from the luminal side with 1300 nm 1 mW or 10 mW light sources, with coherence lengths of 21 and 16 micrometer, respectively. Samples were histologically processed and stained with H&E, EvG and picro-sirius red (PSR) and histological and OCT images were matched. For each sample, the presence of plaque was assessed and the minimal cap thickness was measured by means of histomorphometry and OCT. We found a sensitivity of 6/6 and a specificity of 5/6 for detection of plaques with OCT. Quantitative analysis showed a strong and significant correlation between OCT and histology cap thickness measurements (R2 equals 0.968). Thus, OCT is a sensitive method for detection of plaques, is quantitatively comparable to histology and holds promise as a high-resolution diagnostic tool for visualization of plaque cap thickness.

  12. Diagnosis of atherosclerotic tissue by resonance fluorescence spectroscopy

    Science.gov (United States)

    Neu, Walter; Haase, Karl K.; Tischler, Christian; Nyga, Ralf; Karsch, Karl R.

    1991-05-01

    Resonantly enhanced fluorescence emission induced by a tunable dye laser can be used for the identification of ablated atherosclerotic tissue. This method has been tested with anorganic samples exposed to air and to saline solution. A XeCl excimer laser pulse ((lambda) = 308 nm), delivered by a fused silica optical fiber, causes an efficient ablation of the irradiated samples. The wavelength of the narrow-band dye laser radiation is set to a strong transition of a specific species to be detected in the ablation plume. Taking into account the formation of the plume, the dye laser pulse is applied with a certain delay in order to excite resonantly the selected species in the plume. The resulting resonance fluorescence then is guided by optical fibers to an optical multi-channel analyzer system. Compared to the broad-band fluorescence during excimer laser ablation the resonance fluorescence signal shows a distinct and easily detectable sharp peak. The signal-to-background ratio is improved by one order of magnitude.

  13. Congenital self-healing reticulohistiocytosis - an important diagnostic challenge

    DEFF Research Database (Denmark)

    Jensen, Marie Louise Slott; Bygum, Anette; Clemmensen, Ole;

    2011-01-01

    Aim:  To present current and new knowledge on congenital self-healing reticulohistiocytosis, a benign variant of cutaneous Langerhans cell histiocytosis presenting with skin lesions in the neonatal period. Methods:  We describe and photo document two cases of this rare disease and review the lite......Aim:  To present current and new knowledge on congenital self-healing reticulohistiocytosis, a benign variant of cutaneous Langerhans cell histiocytosis presenting with skin lesions in the neonatal period. Methods:  We describe and photo document two cases of this rare disease and review......, multidisciplinary assessment and follow up are essential. Conclusion:  Our data document how easily the diagnosis congenital self-healing reticulocytosis may be missed and emphasize the importance and value of instant clinical photographing at the neonatal unit and the use of teledermatology whenever congenital...

  14. Effect of biomaterial properties on bone healing in a rabbit tooth extraction socket model

    NARCIS (Netherlands)

    Fisher, J.P.; Lalani, Z.; Bossano, C.M.; Brey, E.M.; Demian, N.; Johnston, C.M.; Dean, D.; Jansen, J.A.; Wong, M.E.; Mikos, A.G.

    2004-01-01

    In this work we sought to understand the effect of biomaterial properties upon healing bone tissue. We hypothesized that a hydrophilic polymer gel implanted into a bone tissue defect would impede the healing process owing to the biomaterial's prevention of protein adsorption and thus cell adhesion.

  15. Novel mussel-inspired injectable self-healing hydrogel with anti-biofouling property.

    Science.gov (United States)

    Li, Lin; Yan, Bin; Yang, Jingqi; Chen, Lingyun; Zeng, Hongbo

    2015-02-18

    A novel mussel-inspired injectable hydrogel with self-healing and anti-biofouling capabilities is developed and it possesses great potential as a drug-delivery carrier. The hydrogel can heal autonomously from repeated structural damage and also effectively prevent non-specific cell attachment and biofilm formation.

  16. The Combination of Three Natural Compounds Effectively Prevented Lung Carcinogenesis by Optimal Wound Healing.

    Directory of Open Access Journals (Sweden)

    Linxin Liu

    Full Text Available The tumor stroma has been described as "normal wound healing gone awry". We explored whether the restoration of a wound healing-like microenvironment may facilitate tumor healing. Firstly, we screened three natural compounds (shikonin, notoginsenoside R1 and aconitine from wound healing agents and evaluated the efficacies of wound healing microenvironment for limiting single agent-elicited carcinogenesis and two-stage carcinogenesis. The results showed that three compounds used alone could promote wound healing but had unfavorable efficacy to exert wound healing, and that the combination of three compounds made up treatment disadvantage of a single compound in wound healing and led to optimal wound healing. Although individual treatment with these agents may prevent cancer, they were not effective for the treatment of established tumors. However, combination treatment with these three compounds almost completely prevented urethane-induced lung carcinogenesis and reduced tumor burden. Different from previous studies, we found that urethane-induced lung carcinogenesis was associated with lung injury independent of pulmonary inflammation. LPS-induced pulmonary inflammation did not increase lung carcinogenesis, whereas decreased pulmonary inflammation by macrophage depletion promoted lung carcinogenesis. In addition, urethane damaged wound healing in skin excision wound model, reversed lung carcinogenic efficacy by the combination of three compounds was consistent with skin wound healing. Further, the combination of these three agents reduced the number of lung cancer stem cells (CSCs by inducing cell differentiation, restoration of gap junction intercellular communication (GJIC and blockade of the epithelial-to-mesenchymal transition (EMT. Our results suggest that restoration of a wound healing microenvironment represents an effective strategy for cancer prevention.

  17. Lumican binds ALK5 to promote epithelium wound healing.

    Directory of Open Access Journals (Sweden)

    Osamu Yamanaka

    Full Text Available Lumican (Lum, a small leucine-rich proteoglycan (SLRP family member, has multiple matricellular functions both as an extracellular matrix component and as a matrikine regulating cell proliferation, gene expression and wound healing. To date, no cell surface receptor has been identified to mediate the matrikine functions of Lum. This study aimed to identify a perspective receptor that mediates Lum effects on promoting wound healing. Transforming growth factor-β receptor 1 (ALK5 was identified as a potential Lum-interacting protein through in silico molecular docking and molecular dynamics. This finding was verified by biochemical pull-down assays. Moreover, the Lum function on wound healing was abrogated by an ALK5-specific chemical inhibitor as well as by ALK5 shRNAi. Finally, we demonstrated that eukaryote-specific post-translational modifications are not required for the wound healing activity of Lum, as recombinant GST-Lum fusion proteins purified from E. coli and a chemically synthesized LumC13 peptide (the last C-terminal 13 amino acids of Lum have similar effects on wound healing in vitro and in vivo.

  18. Cellular and genetic analysis of wound healing in Drosophila larvae.

    Directory of Open Access Journals (Sweden)

    Michael J Galko

    2004-08-01

    Full Text Available To establish a genetic system to study postembryonic wound healing, we characterized epidermal wound healing in Drosophila larvae. Following puncture wounding, larvae begin to bleed but within an hour a plug forms in the wound gap. Over the next couple of hours the outer part of the plug melanizes to form a scab, and epidermal cells surrounding the plug orient toward it and then fuse to form a syncytium. Subsequently, more-peripheral cells orient toward and fuse with the central syncytium. During this time, the Jun N-terminal kinase (JNK pathway is activated in a gradient emanating out from the wound, and the epidermal cells spread along or through the wound plug to reestablish a continuous epithelium and its basal lamina and apical cuticle lining. Inactivation of the JNK pathway inhibits epidermal spreading and reepithelialization but does not affect scab formation or other wound healing responses. Conversely, mutations that block scab formation, and a scabless wounding procedure, provide evidence that the scab stabilizes the wound site but is not required to initiate other wound responses. However, in the absence of a scab, the JNK pathway is hyperinduced, reepithelialization initiates but is not always completed, and a chronic wound ensues. The results demonstrate that the cellular responses of wound healing are under separate genetic control, and that the responses are coordinated by multiple signals emanating from the wound site, including a negative feedback signal between scab formation and the JNK pathway. Cell biological and molecular parallels to vertebrate wound healing lead us to speculate that wound healing is an ancient response that has diversified during evolution.

  19. Self-healing materials with microvascular networks.

    Science.gov (United States)

    Toohey, Kathleen S; Sottos, Nancy R; Lewis, Jennifer A; Moore, Jeffrey S; White, Scott R

    2007-08-01

    Self-healing polymers composed of microencapsulated healing agents exhibit remarkable mechanical performance and regenerative ability, but are limited to autonomic repair of a single damage event in a given location. Self-healing is triggered by crack-induced rupture of the embedded capsules; thus, once a localized region is depleted of healing agent, further repair is precluded. Re-mendable polymers can achieve multiple healing cycles, but require external intervention in the form of heat treatment and applied pressure. Here, we report a self-healing system capable of autonomously repairing repeated damage events. Our bio-inspired coating-substrate design delivers healing agent to cracks in a polymer coating via a three-dimensional microvascular network embedded in the substrate. Crack damage in the epoxy coating is healed repeatedly. This approach opens new avenues for continuous delivery of healing agents for self-repair as well as other active species for additional functionality.

  20. Evaluation of atherosclerotic findings in patients with nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Mohammadi A

    2011-10-01

    Full Text Available Afshin Mohammadi1, Ali Bazazi2, Mohammad Ghasemi-rad21Department of Radiology, Urmia University of Medical Sciences, Urmia, West-Azerbaijan, Iran; 2Student Research Committee, Urmia University of Medical Sciences, Urmia, West-Azerbaijan, IranBackground: Nonalcoholic fatty liver disease (NAFLD, a highly prevalent condition, is a feature of metabolic syndrome and is characterized by excessive accumulation of fat in the liver cells. The purpose of this study was to investigate the association between NAFLD and carotid intima-media thickness (CIMT as an independent risk factor for atherosclerosis.Methods: We examined 250 consecutive patients with ultrasonographically confirmed NAFLD and 85 age-matched and gender-matched controls with normal parenchymal liver echogenicity for determination of CIMT and presence of carotid atherosclerotic plaque.Results: Compared with control subjects, patients with NAFLD showed an increased mean CIMT (0.81 ± 0.14 mm compared with control subjects (0.58 ± 0.15 mm. This difference was statistically significant (P = 0.001. After performing multivariate analysis, the presence of NAFLD was associated with abnormal CIMT independent of other atherogenic risk factors or its association with metabolic syndrome.Conclusion: NAFLD can be an independent risk factor for developing atherosclerosis. Therefore, NAFLD with and without metabolic syndrome can be associated with increased CIMT and increased risk of cardiovascular events in patients with NAFLD incidentally diagnosed on abdominal ultrasonography.Keywords: nonalcoholic fatty liver disease, metabolic syndrome, atherosclerosis, carotid intima media thickness, risk factor

  1. Quantitative profiling of oxylipins in plasma and atherosclerotic plaques of hypercholesterolemic rabbits.

    Science.gov (United States)

    Bojic, Lazar A; McLaren, David G; Harms, Amy C; Hankemeier, Thomas; Dane, Adrie; Wang, Sheng-Ping; Rosa, Ray; Previs, Stephen F; Johns, Douglas G; Castro-Perez, Jose M

    2016-01-01

    Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that affect a broad range of physiological processes, including cell proliferation, inflammation, inflammation resolution, and vascular function. Moreover, oxylipins are readily detectable in plasma, and certain subsets of oxylipins have been detected in human atherosclerotic lesions. Taken together, we set out to produce a detailed quantitative assessment of plasma and plaque oxylipins in a widely used model of atherosclerosis, to identify potential biomarkers of disease progression. We administered regular chow or regular chow supplemented with 0.5% cholesterol (HC) to male New Zealand white rabbits for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our targeted lipidomic analyses of oxylipins on plaques isolated from rabbits fed the HC diet detected 34 oxylipins, 28 of which were in compliance with our previously established quality control acceptance criteria. The arachidonic acid (AA) metabolite derived from the COX pathway, 6-keto-PGF1α was the most abundant plaque oxylipin, followed by the linoleic acid (LA) metabolites 9-HODE, 13-HODE and 9,12,13-TriHOME and the arachidonic acid (AA)-derivatives 11-HETE and 12-HETE. We additionally found that the most abundant oxylipins in plasma were three of the five most abundant oxylipins in plaque, namely 11-HETE, 13-HODE, and 9-HODE. The studies reported here make the first step towards a comprehensive characterization of oxylipins as potentially translatable biomarkers of atherosclerosis.

  2. Healing texts and healing techniques in indigenous Balinese medicine.

    Science.gov (United States)

    McCauley, A P

    1988-01-01

    Case histories of three prominent Balinese healers illustrate various ways that indigenous medical texts are used in healing. Most healers employ mantras, spells and inscriptions from the texts because they believe them to have innate power which can heal. A smaller group of healers are literate in the archaic language used in the palm-leaf medical manuscripts. However, their use of these manuscripts often differs from the literal and unambiguous way that Westerners read medical documents. An examination of Balinese medical manuscripts, in the context of the conventions of Balinese literature, demonstrates the use of these texts to align the body with the macrocosm and to reaffirm the beliefs of the ancestors.

  3. Chinese Food and Cancer Healing

    Directory of Open Access Journals (Sweden)

    Hong Xu

    2006-01-01

    Full Text Available In cancer treatment, apart from studying the effectiveness of chemo or radiotherapy in killing cancer cells, studies should examine ways of reducing drug side effects on patients and ways of enhancing the bodies’ immune system at the same time. Our defence system not only includes immune response, there are also detoxifying enzymes, antioxidant mechanisms, the ability for DNA damage repair and regulation of the hormone metabolism. Harmful environmental oestrogens that enter the human body can cause an increase of 16-α-hydroxyestrone as a harmful estradiol metabolite, the ratio between 16-α-hydroxyestrone and 2-hydroxyestrone relates to the risk of breast cancer. It is suggested that choosing nutritional products (that decrease the amount of 16-α-hydroxyestrone to regulate the hormone metabolism can help with prevention of breast cancer. Increasing the ratio of monounsaturated fatty acid omega-3 (Ω-3 benefits health. Unsaturated fatty acid omega-6 (Ω-6 appears to be easily oxidised which can lead to DNA damage and increase the occurrence of cancer. The most important aspect to this approach is to reduce the ratio between saturated fatty acid and polyunsaturated fatty acid Ω-6, which is harmful to health. Olive oil has a high content of Ω-3 that benefits health. Ω-3 fatty acid can also be obtained from some fish, green vegetables and nuts. Linoleic acid is the most important source of Ω-6 fatty acid. Linolenic acid is the most important source of Ω-3 fatty acid. Natural foods e.g., purslane, is rich in Ω-3; the mustard family vegetables can increase the activity of detoxifying enzymes. Chinese Kiwi fruit drink reduces the side effects of the chemotherapy drug cyclophosphamide, which is also a DNA damaging agent. Soybean, job’s tears, garlic, mushroom varieties and tea have anti-cancer effects. Properly used nutritional products may assist treatment and recovery. Good balanced nutrition is essential for cancer healing.

  4. Regenerative Medicine: Novel Approach in Burn Wound Healing

    Directory of Open Access Journals (Sweden)

    Zare

    2015-06-01

    Full Text Available Context Burn wounds of the skin require a long period to healing, which very often is incomplete, with functional and esthetic consequences for the patients. Stem cells in the traumatized tissue represent the promoters of the healing process and are a primary focus for regenerative medicine, which aims to find and use the triggers for the activation of stem cells of sin tissue. Evidence Acquisition At present, tissue engineering, composite epithelial autografts, multipotent stem cells and combined gene delivery with stem cell therapy are the approaches used in regenerative medicine. Alongside, the development of 3D scaffolds or matrices is a promising adjunct, as studies investigate the multiple uses of these supports for wound repair. Results Application of cells to the burn wound could be performed, either by the bedside, as a non-invasive procedure, or in the operating room, with the use of a matrix, scaffold or dermal substitute. Cell spraying, although under use in clinical setting, is not yet supported by conclusive data. Magnetic resonance imaging, optical imaging and positron emission tomography are currently used to assess the viability and location of stem cells, after transplantation. Conclusions Stem cell therapies in wound care may lessen the morbidities associated with wound healing. An ideal method for the effective administration of stem cells for burn patients has not yet been elucidated. Further comparison of the local and systemic effects in burn patients, associated with each route of stem cell delivery, needs to be performed.

  5. Biologic agents for anterior cruciate ligament healing: A systematic review

    Science.gov (United States)

    Di Matteo, Berardo; Loibl, Markus; Andriolo, Luca; Filardo, Giuseppe; Zellner, Johannes; Koch, Matthias; Angele, Peter

    2016-01-01

    AIM To systematically review the currently available literature concerning the application of biologic agents such as platelet-rich plasma (PRP) and stem cells to promote anterior cruciate ligament (ACL) healing. METHODS A systematic review of the literature was performed on the use of biologic agents (i.e., PRP or stem cells) to favor ACL healing during reconstruction or repair. The following inclusion criteria for relevant articles were used: Clinical reports of any level of evidence, written in English language, on the use of PRP or stem cells during ACL reconstruction/repair. Exclusion criteria were articles written in other languages, reviews, or studies analyzing other applications of PRP/stem cells in knee surgery not related to promoting ACL healing. RESULTS The database search identified 394 records that were screened. A total of 23 studies were included in the final analysis: In one paper stem cells were applied for ACL healing, in one paper there was a concomitant application of PRP and stem cells, whereas in the remaining 21 papers PRP was used. Based on the ACL injury pattern, two papers investigated biologic agents in ACL partial tears whereas 21 papers in ACL reconstruction. Looking at the quality of the available literature, 17 out of 21 studies dealing with ACL reconstruction were randomized controlled trials. Both studies on ACL repair were case series. CONCLUSION There is a paucity of clinical trials investigating the role of stem cells in promoting ACL healing both in case of partial and complete tears. The role of PRP is still controversial and the only advantage emerging from the literature is related to a better graft maturation over time, without documenting beneficial effects in terms of clinical outcome, bone-graft integration and prevention of bony tunnel enlargement. PMID:27672573

  6. The alpha3 laminin subunit, alpha6beta4 and alpha3beta1 integrin coordinately regulate wound healing in cultured epithelial cells and in the skin

    DEFF Research Database (Denmark)

    Goldfinger, L E; Hopkinson, S B; deHart, G W;

    1999-01-01

    Previously, we demonstrated that proteolytic processing within the globular domain of the alpha3 subunit of laminin-5 (LN5) converts LN5 from a cell motility-inducing factor to a protein complex that can trigger the formation of hemidesmosomes, certain cell-matrix attachment sites found in epithe......Previously, we demonstrated that proteolytic processing within the globular domain of the alpha3 subunit of laminin-5 (LN5) converts LN5 from a cell motility-inducing factor to a protein complex that can trigger the formation of hemidesmosomes, certain cell-matrix attachment sites found...... in epithelial cells. We have prepared a monoclonal antibody (12C4) whose epitope is located toward the carboxy terminus of the globular domain of the alpha3 laminin subunit. This epitope is lost from the alpha3 subunit as a consequence of proteolytic processing. Antibody 12C4 stains throughout the matrix...

  7. Interior design and healing architecture

    DEFF Research Database (Denmark)

    Mogensen, Jeppe; Poulsen, Søren Bolvig; Hansen, Allan Grutt

    2015-01-01

    and materials are rather limited. To compliment research in hospital interior design with particular focus on the use of interior textiles, this pilot study explores if the patients’ preferences for more home-like hospital interiors can be linked to a preference for textile-based furniture and materials...... the interpretation of the quantitative and qualitative data. 21% of the participants requested interior design improvements, and had a pronounced preference for the textile-based furniture and materials. For this particular group, the link between home-like hospital interiors and textile materials were thus......Hospital design is today influenced by the design concept healing architecture, stating that the patients’ healing process is promoted through accommodating physical surroundings. However, despite the increasing amount of research in the field of healing architecture, research on interior design...

  8. Revisiting perioperative chemotherapy: the critical importance of targeting residual cancer prior to wound healing

    International Nuclear Information System (INIS)

    Scientists and physicians have long noted similarities between the general behavior of a cancerous tumor and the physiological process of wound healing. But it may be during metastasis that the parallels between cancer and wound healing are most pronounced. And more particularly and for the reasons detailed in this paper, any cancer remaining after the removal of a solid tumor, whether found in micrometastatic deposits in the stroma or within the circulation, may be heavily dependent on wound healing pathways for its further survival and proliferation. If cancer cells can hijack the wound healing process to facilitate their metastatic spread and survival, then the period immediately after surgery may be a particularly vulnerable period of time for the host, as wound healing pathways are activated and amplified after the primary tumor is removed. Given that we often wait 30 days or more after surgical removal of the primary tumor before initiating adjuvant chemotherapy to allow time for the wound to heal, this paper challenges the wisdom of that clinical paradigm, providing a theoretical rationale for administering therapy during the perioperative period. Waiting for wound healing to occur before initiating adjuvant therapies may be seriously compromising their effectiveness, and patients subsequently rendered incurable as a result of this wait. Clinical trials to establish the safety and effectiveness of administering adjuvant therapies perioperatively are needed. These therapies should target not only the residual cancer cells, but also the wound healing pathway utilized by these cells to proliferate and metastasize

  9. Improvement of renal function after opening occluded atherosclerotic renal arteries.

    Science.gov (United States)

    Kanamori, Hiroshi; Toma, Masanao; Fukatsu, Atsushi

    2009-09-01

    Percutaneous transluminal renal angioplasty (PTRA) with stenting has been effective in the control of hypertension, renal function and pulmonary edema caused by atherosclerotic renal artery stenosis (ARAS). However, concerning the viability of renal function, this procedure has not been fully established, especially in the presence of renal atrophy or severe renal parenchymal disease. We report a dramatically improved case of acute renal failure caused by acute worsening ARAS treated by stenting. A 72-year-old female was admitted for accelerated renal dysfunction (serum ceatinine; 1.2-2.3 mg/dl) and hypertension (190/100 mmHg). At 10 days after admission, the patient's serum ceatinine increased to 6.7 mg/dl, her pulmonary edema was exaggerated and hemodialysis was required. Ultrasonography showed bilateral high-echoic kidneys, but no apparent finding of renal artery stenosis (RAS). At day 15, computed tomographic angiography indicated bilateral ostial RAS. Renal angiography demonstrated total occlusion of the right and severe (90%) disease in the left. ARAS was diagnosed by intravascular ultrasonography. The guidewire was inserted in both renal arteries, PTRA with stenting was performed in the right and a stent was directly implanted in the left. Immediately, each kidney enlarged to almost normal size, leading to satisfactory urination. She was released from hemodialysis the next day since her serum creatinine was normal and the pulmonary edema was improved. Although there is still no reliable prognostic factor including resistive index or kidney size, it is important that PTRA with stenting in ARAS should be considered in a case of accelerated renal dysfunction because of the possible improvement. PMID:19726830

  10. Optical detection of structural changes in human carotid atherosclerotic plaque

    Science.gov (United States)

    Korol, R. M.; Canham, P. B.; Finlay, H. M.; Hammond, R. R.; Quantz, M.; Ferguson, G. G.; Liu, L. Y.; Lucas, A. R.

    2005-08-01

    Background: Arterial bifurcations are commonly the sites of developing atherosclerotic plaque that lead to arterial occlusions and plaque rupture (myocardial infarctions and strokes). Laser induced fluorescence (LIF) spectroscopy provides an effective nondestructive method supplying spectral information on extracellular matrix (ECM) protein composition, specifically collagen and elastin. Purpose: To investigate regional differences in the ECM proteins -- collagen I, III and elastin in unstable plaque by analyzing data from laser-induced fluorescence spectroscopy of human carotid endarterectomy specimens. Methods: Gels of ECM protein extracts (elastin, collagen types I & III) were measured as reference spectra and internal thoracic artery segments (extra tissue from bypass surgery) were used as tissue controls. Arterial segments and the endarterectomy specimens (n=21) were cut into 5mm cross-sectional rings. Ten fluorescence spectra per sampling area were then recorded at 5 sites per ring with argon laser excitation (357nm) with a penetration depth of 200 μm. Spectra were normalized to maximum intensity and analyzed using multiple regression analysis. Tissue rings were fixed in formalin (within 3 hours of surgery), sectioned and stained with H&E or Movat's Pentachrome for histological analysis. Spectroscopy data were correlated with immunohistology (staining for elastin, collagen types I, III and IV). Results: Quantitative fluorescence for the thoracic arteries revealed a dominant elastin component on the luminal side -- confirmed with immunohistology and known artery structure. Carotid endarterectomy specimens by comparison had a significant decrease in elastin signature and increased collagen type I and III. Arterial spectra were markedly different between the thoracic and carotid specimens. There was also a significant elevation (pdetected in the carotid specimens.

  11. Atherosclerotic cardiovascular disease in patients with chronic inflammatory joint disorders.

    Science.gov (United States)

    Agca, R; Heslinga, S C; van Halm, V P; Nurmohamed, M T

    2016-05-15

    Inflammatory joint disorders (IJD), including rheumatoid arthritis (RA), ankylosing spondylitis (ASp) and psoriatic arthritis (PsA), are prevalent conditions worldwide with a considerable burden on healthcare systems. IJD are associated with increased cardiovascular (CV) disease-related morbidity and mortality. In this review, we present an overview of the literature. Standardised mortality ratios are increased in IJD compared with the general population, that is, RA 1.3-2.3, ASp 1.6-1.9 and PsA 0.8-1.6. This premature mortality is mainly caused by atherosclerotic events. In RA, this CV risk is comparable to that in type 2 diabetes. Traditional CV risk factors are more often present and partially a consequence of changes in physical function related to the underlying IJD. Also, chronic systemic inflammation itself is an independent CV risk factor. Optimal control of disease activity with conventional synthetic, targeted synthetic and biological disease-modifying antirheumatic drugs decreases this excess risk. High-grade inflammation as well as anti-inflammatory treatment alter traditional CV risk factors, such as lipids. In view of the above-mentioned CV burden in patients with IJD, CV risk management is necessary. Presently, this CV risk management is still lacking in usual care. Patients, general practitioners, cardiologists, internists and rheumatologists need to be aware of the substantially increased CV risk in IJD and should make a combined effort to timely initiate CV risk management in accordance with prevailing guidelines together with optimal control of rheumatic disease activity. CV screening and treatment strategies need to be implemented in usual care. PMID:26888573

  12. Hypercalcemia Leads to Delayed Corneal Wound Healing in Ovariectomized Rats.

    Science.gov (United States)

    Nagai, Noriaki; Ogata, Fumihiko; Kawasaki, Naohito; Ito, Yoshimasa; Funakami, Yoshinori; Okamoto, Norio; Shimomura, Yoshikazu

    2015-01-01

    Hypercalcemia is often observed in postmenopausal women as well as in patients with primary hyperparathyroidism or malignant tumors. In this study, we investigated the relationship between calcium ion (Ca(2+)) levels in lacrimal fluid and the rate of corneal wound healing in hypercalcemia using ovariectomized (OVX) rat debrided corneal epithelium. We also determined the effects of Ca(2+) levels on cell adhesion, proliferation and viability in a human cornea epithelial cell line (HCE-T). The calcium content in bones of OVX rats decreased after ovariectomy. Moreover, the Ca(2+) content in the blood of OVX rats was increased 1 month after ovariectomy, and decreased. The Ca(2+) content in the lacrimal fluid of OVX rats was also increased after ovariectomy, and then decreased similarly as in blood. Corneal wound healing in OVX rats was delayed in comparison with Sham rats (control rats), and a close relationship was observed between the Ca(2+) levels in lacrimal fluid and the rate of corneal wound healing in Sham and OVX rats (y=-0.7863x+8.785, R=0.78, n=25). In addition, an enhancement in Ca(2+) levels caused a decrease in the viability in HCE-T cells. It is possible that enhanced Ca(2+) levels in lacrimal fluid may cause a decrease in the viability of corneal epithelial cells, resulting in a delay in corneal wound healing. These findings provide significant information that can be used to design further studies aimed at reducing corneal damage of patients with hypercalcemia.

  13. Modeling self-healing materials

    Directory of Open Access Journals (Sweden)

    Anna C. Balazs

    2007-09-01

    Full Text Available We describe recent computational studies to design such systems as ‘artificial leukocytes’ that facilitate the healing of damaged substrates, polymer nanocomposites where nanoparticles are driven to fill cracks in fractured surfaces, and polymer gels that effectively act as a ‘skin’ by signaling mechanical impact. Computational research into self-healing materials is still in its infancy. However, progress in this field can ultimately facilitate the fabrication of the next generation of adaptive materials that both monitor their structural integrity and mend themselves before any catastrophic failure can occur.

  14. Self healing of defected graphene

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jianhui; Shi, Tuwan; Cai, Tuocheng; Wu, Xiaosong; Yu, Dapeng [School of Physics, Peking University, Beijing 100871 (China); State Key Laboratory for Artificial Microstructure and Mesoscopic Physics, Peking University, Beijing 100871 (China); Xu, Tao; Sun, Litao [SEU-FEI Nano-Pico Center, Key Laboratory of MEMS of Ministry of Education, Southeast University, Nanjing 210096 (China)

    2013-03-11

    For electronics applications, defects in graphene are usually undesirable because of their ability to scatter charge carriers, thereby reduce the carrier mobility. It would be extremely useful if the damage can be repaired. In this work, we employ Raman spectroscopy, X-ray photoemission spectroscopy, transmission electron microscopy, and electrical measurements to study defects in graphene introduced by argon plasma bombardment. We have found that majority of these defects can be cured by a simple thermal annealing process. The self-healing is attributed to recombination of mobile carbon adatoms with vacancies. With increasing level of plasma induced damage, the self-healing becomes less effective.

  15. Chitosan-alginate membranes accelerate wound healing.

    Science.gov (United States)

    Caetano, Guilherme Ferreira; Frade, Marco Andrey Cipriani; Andrade, Thiago Antônio Moretti; Leite, Marcel Nani; Bueno, Cecilia Zorzi; Moraes, Ângela Maria; Ribeiro-Paes, João Tadeu

    2015-07-01

    The purpose of this study was to evaluate the efficacy of chitosan-alginate membrane to accelerate wound healing in experimental cutaneous wounds. Two wounds were performed in Wistar rats by punching (1.5 cm diameter), treated with membranes moistened with saline solution (CAM group) or with saline only (SL group). After 2, 7, 14, and 21 days of surgery, five rats of each group were euthanized and reepithelialization was evaluated. The wounds/scars were harvested for histological, flow cytometry, neutrophil infiltrate, and hydroxyproline analysis. CAM group presented higher inflammatory cells recruitment as compared to SL group on 2(nd) day. On the 7(th) day, CAM group showed higher CD11b(+) level and lower of neutrophils than SL group. The CAM group presented higher CD4(+) cells influx than SL group on 2(nd) day, but it decreased during the follow up and became lower on 14(th) and 21(st) days. Higher fibroplasia was noticed on days 7 and 14 as well as higher collagenesis on 21(st) in the CAM group in comparison to SL group. CAM group showed faster reepithelialization on 7(th) day than SL group, although similar in other days. In conclusion, chitosan-alginate membrane modulated the inflammatory phase, stimulated fibroplasia and collagenesis, accelerating wound healing process in rats.

  16. Shedding Light on a New Treatment for Diabetic Wound Healing: A Review on Phototherapy

    Directory of Open Access Journals (Sweden)

    Nicolette N. Houreld

    2014-01-01

    Full Text Available Impaired wound healing is a common complication associated with diabetes with complex pathophysiological underlying mechanisms and often necessitates amputation. With the advancement in laser technology, irradiation of these wounds with low-intensity laser irradiation (LILI or phototherapy, has shown a vast improvement in wound healing. At the correct laser parameters, LILI has shown to increase migration, viability, and proliferation of diabetic cells in vitro; there is a stimulatory effect on the mitochondria with a resulting increase in adenosine triphosphate (ATP. In addition, LILI also has an anti-inflammatory and protective effect on these cells. In light of the ever present threat of diabetic foot ulcers, infection, and amputation, new improved therapies and the fortification of wound healing research deserves better prioritization. In this review we look at the complications associated with diabetic wound healing and the effect of laser irradiation both in vitro and in vivo in diabetic wound healing.

  17. The content of copper and zinc in human ulcered atherosclerotic plaque

    Directory of Open Access Journals (Sweden)

    Radak Đorđe

    2004-01-01

    Full Text Available INTRODUCTION Copper and zinc have significant antiatherogenic effect influencing activity of antioxidant enzyms (giutathion-peroxidase i superoxid-dismutase, mechanism of apoptosis and other mechanisms. Few studies showed increased copper and zinc concentration in atherosclerotic plaque in comparison to normal vascular tissue. AIM The aim of the study was to compare copper and zinc concentrations in carotid artery tissue without significant atherosclerotic changes and human ulcered atherosclerotic plaque. MATERIAL AND METHODS Study was conducted on 66 patients. Carotid endarterectomy due to the significant carotid atherosclerotic changes with cerebrovascular disorders was performed in 54 patients (81.8%. Control group consisted of 12 patients (18.2% without carotid atherosclerotic changes operated due to the symptomatic kinking and coiling of carotid artery. Operated group consisted of 38 man (62.96% and 16 woman (37.04%. Control group had the same number of patients: six men (50% and six women (50%. Preoperatively, all patients were examined by vascular surgeon, neurologist and cardiologist. Duplex sonografy of carotid and vertebral arteries was performed by Aloca DSD 630 ultrasound with mechanical and linear transducer 7.7 MHz. Indication for surgical treatment was obtained according to non-invasive diagnostic protocol and neurological symptoms. Copper and zinc concentration in human ulcered atherosclerotic plaque and carotid artery segment were estimated by spectophotometry (Varian AA-5. RESULTS Average age of our patients was 59.8±8.1 years. For males average age was 76.1 ±9.8 years. And for females 42.4±5.8 years. In group with carotid endarterectomy female patients were significantly younger than male patients (p<0.01. In group with carotid endarterectomy clinically determined neurological disorders were found in 47 patients (87.03%-35 male (74.47% and 12 female patients (25.53%. Regarding risk factors for cardiovascular diseases, no

  18. Abnormal pigmentation within cutaneous scars: A complication of wound healing

    Directory of Open Access Journals (Sweden)

    Sarah Chadwick

    2012-01-01

    Full Text Available Abnormally pigmented scars are an undesirable consequence of cutaneous wound healing and are a complication every single individual worldwide is at risk of. They present a challenge for clinicians, as there are currently no definitive treatment options available, and render scars much more noticeable making them highly distressing for patients. Despite extensive research into both wound healing and the pigment cell, there remains a scarcity of knowledge surrounding the repigmentation of cutaneous scars. Pigment production is complex and under the control of many extrinsic and intrinsic factors and patterns of scar repigmentation are unpredictable. This article gives an overview of human skin pigmentation, repigmentation following wounding and current treatment options.

  19. Congenital self-healing reticulohistiocytosis: a case report

    Directory of Open Access Journals (Sweden)

    Shricharith Shetty

    2014-07-01

    Full Text Available Congenital self-healing reticulohistiocytosis (CSHRH is a benign type of Langerhans cell histiocytosis (LCH also known as Hashimoto-Pritzker disease. Clinically it presents with skin lesions at birth or in neonatal period, usually without any systemic involvement. Lesions often heal spontaneously in period of weeks to months. We report a case of CSHRH presenting with skin lesions at birth, describing need to make an early diagnosis and to have a multidisciplinary approach with regular follow-up, in managing this rare type of LCH.

  20. Healing of Chronic Wounds through Systemic Effects of Electromagnetic Fields

    Science.gov (United States)

    Cañedo, L.; Trigos, I.; García-Cantú, R.; Godina-Nava, J. J.; Serrano, G.

    2002-08-01

    Extremely low frequency electromagnetic fields (ELF) were configured to interact with peripheral blood mononuclear cells (PBMC). These ELF were applied in the arm to five patients with chronic wounds resistant to medical and surgical treatment. Wound healing began in all patients during the first two weeks after ELF exposure permiting their previously unresponsive chronic wounds to function as internal controls. All lesions were cured or healed >70% in less than four months. Systemic effects were explained by ELF activation of PBMC and their transportation through the blood to the affected site. This therapy is effective in selected patients with chronic wounds.