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Sample records for cell msc paradigm

  1. A new mesenchymal stem cell (MSC paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype.

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    Ruth S Waterman

    Full Text Available BACKGROUND: Our laboratory and others reported that the stimulation of specific Toll-like receptors (TLRs affects the immune modulating responses of human multipotent mesenchymal stromal cells (hMSCs. Toll-like receptors recognize "danger" signals, and their activation leads to profound cellular and systemic responses that mobilize innate and adaptive host immune cells. The danger signals that trigger TLRs are released following most tissue pathologies. Since danger signals recruit immune cells to sites of injury, we reasoned that hMSCs might be recruited in a similar way. Indeed, we found that hMSCs express several TLRs (e.g., TLR3 and TLR4, and that their migration, invasion, and secretion of immune modulating factors is drastically affected by specific TLR-agonist engagement. In particular, we noted diverse consequences on the hMSCs following stimulation of TLR3 when compared to TLR4 by our low-level, short-term TLR-priming protocol. PRINCIPAL FINDINGS: Here we extend our studies on the effect on immune modulation by specific TLR-priming of hMSCs, and based on our findings, propose a new paradigm for hMSCs that takes its cue from the monocyte literature. Specifically, that hMSCs can be polarized by downstream TLR signaling into two homogenously acting phenotypes we classify here as MSC1 and MSC2. This concept came from our observations that TLR4-primed hMSCs, or MSC1, mostly elaborate pro-inflammatory mediators, while TLR3-primed hMSCs, or MSC2, express mostly immunosuppressive ones. Additionally, allogeneic co-cultures of TLR-primed MSCs with peripheral blood mononuclear cells (PBMCs predictably lead to suppressed T-lymphocyte activation following MSC2 co-culture, and permissive T-lymphocyte activation in co-culture with MSC1. SIGNIFICANCE: Our study provides an explanation to some of the conflicting reports on the net effect of TLR stimulation and its downstream consequences on the immune modulating properties of stem cells. We further

  2. Mesenchymal stem cell 1 (MSC1-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis.

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    Ruth S Waterman

    Full Text Available BACKGROUND: Currently, there are many promising clinical trials using mesenchymal stem cells (MSCs in cell-based therapies of numerous diseases. Increasingly, however, there is a concern over the use of MSCs because they home to tumors and can support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promoted tumor growth and favored angiogenesis. In parallel studies, we also developed a new approach to induce the conventional mixed pool of MSCs into two uniform but distinct phenotypes we termed MSC1 and MSC2. METHODOLOGY/PRINCIPAL FINDINGS: Here we tested the in vitro and in vivo stability of MSC1 and MSC2 phenotypes as well as their effects on tumor growth and spread. In vitro co-culture of MSC1 with various cancer cells diminished growth in colony forming units and tumor spheroid assays, while conventional MSCs or MSC2 co-culture had the opposite effect in these assays. Co-culture of MSC1 and cancer cells also distinctly affected their migration and invasion potential when compared to MSCs or MSC2 treated samples. The expression of bioactive molecules also differed dramatically among these samples. MSC1-based treatment of established tumors in an immune competent model attenuated tumor growth and metastasis in contrast to MSCs- and MSC2-treated animals in which tumor growth and spread was increased. Also, in contrast to these groups, MSC1-therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mast cell degranulation. CONCLUSION/SIGNIFICANCE: These observations indicate that the MSC1 and MSC2 phenotypes may be convenient tools for the discovery of critical components of the tumor stroma. The continued investigation of these cells may help ensure that cell based-therapy is used safely and effectively in human disease.

  3. TLR4 plays a crucial role in MSC-induced inhibition of NK cell function

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    Lu, Ying [No. 307 Hospital of the Chinese People' s Liberation Army, Beijing (China); Liu, Jin; Liu, Yang; Qin, Yaru [Beijing Institute of Radiation Medicine, Beijing (China); Luo, Qun [No. 307 Hospital of the Chinese People' s Liberation Army, Beijing (China); Wang, Quanli, E-mail: 13691110351@163.com [No. 307 Hospital of the Chinese People' s Liberation Army, Beijing (China); Duan, Haifeng, E-mail: duanhf0720@163.com [Beijing Institute of Radiation Medicine, Beijing (China)

    2015-08-21

    Mesenchymal stem cells (MSC) are a kind of stromal cell within the tumor microenvironment. In our research, MSC derived from acute myeloid leukemia patients' bone marrow (AML-MSC) and lung cancer tissues (LC-MSC) as well as normal bone marrow-derived MSC (BM-MSC) cultured in conditioned medium of HeLa cells were found to have higher expressions of Toll-like receptor (TLR4) mRNA compared with BM-MSC. The sorted TLR4-positive MSC (TLR4+ MSC) differed in cytokine (interleukin-6, interleukin-8, and monocyte chemoattractant protein-1) secretion from those of unsorted MSC. MSC was reported to inhibit natural killer (NK) cell proliferation and function. In this research, we confirmed that TLR4+ MSC aggravate this suppression. Furthermore, when TLR4 in the sorted cells were stimulated by LPS or following blocked by antibody, the suppression on NK cell proliferation and cytotoxicity were more intensive or recovered respectively. Compared to unsorted MSC, NKG2D receptor expression on NK cells were also inhibited by TLR4+ MSC. These findings suggest that activation of TLR4 pathway is important for TLR4+ MSC and MSC to obstruct anti-tumor immunity by inhibiting NK cell function, which may provide a potential stroma-targeted tumor therapy. - Highlights: • TLR4+ MSC inhibit NK cell proliferation in vivo and in vitro. • TLR4+ MSC inhibit NKG2D expression on NK cells and NK cell cytotoxicity. • The distinguished cytokine expression of TLR4+ MSC may contribute to the inhibition on NK cell function.

  4. TLR4 plays a crucial role in MSC-induced inhibition of NK cell function

    International Nuclear Information System (INIS)

    Mesenchymal stem cells (MSC) are a kind of stromal cell within the tumor microenvironment. In our research, MSC derived from acute myeloid leukemia patients' bone marrow (AML-MSC) and lung cancer tissues (LC-MSC) as well as normal bone marrow-derived MSC (BM-MSC) cultured in conditioned medium of HeLa cells were found to have higher expressions of Toll-like receptor (TLR4) mRNA compared with BM-MSC. The sorted TLR4-positive MSC (TLR4+ MSC) differed in cytokine (interleukin-6, interleukin-8, and monocyte chemoattractant protein-1) secretion from those of unsorted MSC. MSC was reported to inhibit natural killer (NK) cell proliferation and function. In this research, we confirmed that TLR4+ MSC aggravate this suppression. Furthermore, when TLR4 in the sorted cells were stimulated by LPS or following blocked by antibody, the suppression on NK cell proliferation and cytotoxicity were more intensive or recovered respectively. Compared to unsorted MSC, NKG2D receptor expression on NK cells were also inhibited by TLR4+ MSC. These findings suggest that activation of TLR4 pathway is important for TLR4+ MSC and MSC to obstruct anti-tumor immunity by inhibiting NK cell function, which may provide a potential stroma-targeted tumor therapy. - Highlights: • TLR4+ MSC inhibit NK cell proliferation in vivo and in vitro. • TLR4+ MSC inhibit NKG2D expression on NK cells and NK cell cytotoxicity. • The distinguished cytokine expression of TLR4+ MSC may contribute to the inhibition on NK cell function

  5. Mesenchymal Stem Cell (MSC) Aggregate Formation in vivo

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    Bartosh, Thomas J.; Ylostalo, Joni H.

    2016-01-01

    Human mesenchymal stem/progenitor cells (MSCs) isolated from various adult tissues show remarkable therapeutic potential and are being employed in clinical trials for the treatment of numerous diseases (Prockop et al., 2010). While routes of cell administration vary, profound beneficial effects of MSCs in animal models have been observed following intraperitoneal injections of the cells (Roddy et al., 2011). Similar to MSC spheres formed in culture under conditions where attachment to plastic is not permitted (Bartosh et al., 2010), MSCs injected into the peritoneum of mice spontaneously aggregate into 3D sphere-like structures (Bartosh et al., 2013). During the process of sphere assembly and compaction, MSCs upregulate expression of numerous therapeutic anti-inflammatory and immune modulatory factors. Here we describe the method we previously used for the generation of human bone marrow-derived MSC aggregates/spheres in vivo (Bartosh et al., 2013). By tagging the MSCs with green fluorescent protein (GFP), the aggregates formed can be easily visualized, collected and analyzed for changes in cellular properties and interactions with host immune cells.

  6. Mesenchymal stem cells (MSC prevented the progression of renovascular hypertension, improved renal function and architecture.

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    Elizabeth B Oliveira-Sales

    Full Text Available Renovascular hypertension induced by 2 Kidney-1 Clip (2K-1C is a renin-angiotensin-system (RAS-dependent model, leading to renal vascular rarefaction and renal failure. RAS inhibitors are not able to reduce arterial pressure (AP and/or preserve the renal function, and thus, alternative therapies are needed. Three weeks after left renal artery occlusion, fluorescently tagged mesenchymal stem cells (MSC (2×10(5 cells/animal were injected weekly into the tail vein in 2K-1C hypertensive rats. Flow cytometry showed labeled MSC in the cortex and medulla of the clipped kidney. MSC prevented a further increase in the AP, significantly reduced proteinuria and decreased sympathetic hyperactivity in 2K-1C rats. Renal function parameters were unchanged, except for an increase in urinary volume observed in 2K-1C rats, which was not corrected by MSC. The treatment improved the morphology and decreased the fibrotic areas in the clipped kidney and also significantly reduced renal vascular rarefaction typical of 2K-1C model. Expression levels of IL-1β, TNF-α angiotensinogen, ACE, and Ang II receptor AT1 were elevated, whereas AT2 levels were decreased in the medulla of the clipped kidney. MSC normalized these expression levels. In conclusion, MSC therapy in the 2K-1C model (i prevented the progressive increase of AP, (ii improved renal morphology and microvascular rarefaction, (iii reduced fibrosis, proteinuria and inflammatory cytokines, (iv suppressed the intrarenal RAS, iv decreased sympathetic hyperactivity in anesthetized animals and v MSC were detected at the CNS suggesting that the cells crossed the blood-brain barrier. This therapy may be a promising strategy to treat renovascular hypertension and its renal consequences in the near future.

  7. Therapeutic use of human mesenchymal stem cells (MSC) for the treatment of radio-induced diseases

    International Nuclear Information System (INIS)

    Ionising radiation can induce toxic effects on body. They provoke physiological modifications of tissues and organs which can be lethal. Total body irradiation or local abdominal irradiation can induce serious complications. Intestine is the first tissue concerned by these side effects. Radiation induces malabsorption of the intestine and lost of it integrity. Radio-induced physiopathological effects on intestine could lead to distant effects on other tissues and organs such as liver. The actual treatments have a limited efficiency or are not adapted to gastrointestinal damages. Indeed, in this type of lesions, the heterogeneous systems which are concerned and the gravity of lesions complicates the medical care. Our purpose is to show that cell therapy using human mesenchymal stem cells (MSC) constitutes resolution in this type of illness. The works which are presented in this thesis show that MSC are multi-potent and have heterogeneous expression of molecules. These cells are able to establish themselves in many organs and tissues after injection into irradiated body. Thus we have shown that MSC can prevent the small intestine from radio-induced damages. Indeed we demonstrate that through their actions on gut, MSC can indirectly restore hepatic integrity. (author)

  8. Optimasi Penambahan Colcemid pada Karyotyping Kultur Mecenchymal Stem Cells (MSC Mencit

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    Ratih Rinendyaputri

    2016-02-01

    Full Text Available AbstractControl of the genetic stability of stem cells prior to the conduct of therapy is essential to prevent effects such as stem cell transformation. Karyotyping is a conventional technique to conduct an analysis of the number and structure of chromosomes. The analysis can only be performed on metaphase stage that needs to be optimized to get the cell at that stage because the length of the cell cycle are different in the each cell types. This study aims to obtain an optimal time to get MSC at metaphase stage. The study was conducted at the stem cell laboratory of Center for Biomedical and Basic Technology of Health. The event begins with isolation using flushing technique at the femur and tibia of mice. Furthermore, the culture in vitro and induction colcemid 0,25μg/ml for 8,16 and 24 hours to get the MSC at metaphase stage. KCl solution with a concentration of 0.075 M and 0,045 M used as a solvent hipotonis. Results showed that 16 hours of induction colcemid 0,25μg/ml in 0.075 M KCl solution usage percentage of MSC who are at metaphase stage and do the highest analysis (p<0.05. In this study 16 hours induction colcemid 0,25μg/ml is the optimal time to obtain metaphase stage of the MSC from bone marrow of mice.Keywords: mecenchymal stem cell, karyotyping, colcemidAbstrakKontrol terhadap stabilitas genetik pada sel punca sebelum pelaksanan terapi merupakan hal yang penting untuk mencegah efek seperti transformasi sel punca yang dapat terjadi. Secara konvensional dapat dilakukan karyotyping untuk melakukan analisis terhadap jumlah dan struktur kromosom. Analisis hanya dapat dilakukan pada tahap metafase sehingga perlu dilakukan optimasi untuk mendapatkan sel pada tahap tersebut mengingat panjang siklus sel setiap jenis sel berbeda. Penelitian ini bertujuan untuk memperoleh waktu yang optimal untuk mendapatkan MSC pada tahap metafase. Penelitian dilakukan di Laboratorium stem cell Pusat Biomedis dan Teknologi Dasar Kesehatan Badan Litbangkes

  9. Cell therapy medicinal product regulatory framework in Europe and its application for MSC based therapy development

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    Janis eAncans

    2012-08-01

    Full Text Available Advanced therapy medicinal products (ATMPs, including cell therapy products, form a new class of medicines in the European Union. Since ATMPs are at the forefront of scientific innovation in medicine, specific regulatory framework has been developed for these medicines and implemented from 2009. The Committee for Advanced Therapies (CAT has been established at European Medicines Agency (EMA for centralized classification, certification and evaluation procedures, and other ATMP related tasks. Guidance documents, initiatives and interaction platforms are available to make the new framework more accessible for small and medium-sized enterprises, academia, hospitals and foundations. Good understanding of centralised and national components of the regulatory system is required to plan product development. It is in the best interests of cell therapy developers to utilise provided resources starting with the preclinical stage. Whilst there have not been mesenchymal stem cell (MSC based medicine authorisations in the EU, three MSC products have received marketing approval in other regions since 2011. Information provided on regulatory requirements, procedures and initiatives is aimed to facilitate MSC based medicinal product development and authorisation in the EU.

  10. Suicide gene reveals the myocardial neovascularization role of mesenchymal stem cells overexpressing CXCR4 (MSC(CXCR4.

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    Jialiang Liang

    Full Text Available BACKGROUND: Our previous studies indicated that MSC(CXCR4 improved cardiac function after myocardial infarction (MI. This study was aimed to investigate the specific role of MSC(CXCR4 in neovascularization of infarcted myocardium using a suicide gene approach. METHODS: MSCs were transduced with either lentivirus-null vector/GFP (MSC(Null as control or vector encoding for overexpressing CXCR4/GFP. The MSC derived-endothelial cell (EC differentiation was assessed by a tube formation assay, Dil-ac-LDL uptake, EC marker expression, and VE-cadherin promoter activity assay. Gene expression was analyzed by quantitative RT-PCR or Western blot. The suicide gene approach was under the control of VE-cadherin promoter. In vivo studies: Cell patches containing MSC(Null or MSC(CXCR4 were transduced with suicide gene and implanted into the myocardium of MI rat. Rats received either ganciclovir (GCV or vehicle after cell implantation. After one month, the cardiac functional changes and neovascularization were assessed by echocardiography, histological analysis, and micro-CT imaging. RESULTS: The expression of VEGF-A and HIF-1α was significantly higher in MSC(CXCR4 as compared to MSC(Null under hypoxia. Additionally, MSC(CXCR4 enhanced new vessel formation and EC differentiation, as well as STAT3 phosphorylation under hypoxia. STAT3 participated in the transcription of VE-cadherin in MSC(CXCR4 under hypoxia, which was inhibited by WP1066 (a STAT3 inhibitor. In addition, GCV specifically induced death of ECs with suicide gene activation. In vivo studies: MSC(CXCR4 implantation promoted cardiac functional restoration, reduced infarct size, improved cardiac remodeling, and enhanced neovascularization in ischemic heart tissue. New vessels derived from MSC(CXCR4 were observed at the injured heart margins and communicated with native coronary arteries. However, the derived vessel networks were reduced by GCV, reversing improvement of cardiac function. CONCLUSION: The

  11. Novel isolation strategy to deliver pure fetal-origin and maternal-origin mesenchymal stem cell (MSC) populations from human term placenta.

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    Patel, J; Shafiee, A; Wang, W; Fisk, N M; Khosrotehrani, K

    2014-11-01

    The placenta is an abundant source of mesenchymal stem/stromal cells (MSC). Although presumed of translationally-advantageous fetal origin, the literature instead suggests a high incidence of either contaminating or pure maternal MSC. Despite definitional criteria that MSC are CD34-, increasing evidence suggests that fetal MSC may be CD34 positive in vivo. We flow sorted term placental digests based on CD34+ expression and exploited differential culture media to isolate separately pure fetal and maternal MSC populations. This method has considerable translational implications, in particular to clinical trials underway with "placental" MSC of uncertain or decidual origin.

  12. Combined MSC-Secreted Factors and Neural Stem Cell Transplantation Promote Functional Recovery of PD Rats.

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    Yao, Yuan; Huang, Chen; Gu, Ping; Wen, Tieqiao

    2016-01-01

    Stem cell transplantation has enormous potential for the treatment of neurodegenerative disorders like Parkinson's disease (PD). Mesenchymal stem cells (MSCs) have attracted much attention because they can secrete a wide variety of cellular factors that promote cell growth. In this study, we prepared a conditioned medium (CM) using lyophilized MSC culture medium that contained the secretome of MSCs and applied this CM to the culture of neural stem cells (CM-NSCs) for the transplantation of PD model rats. Quantitative real-time PCR, Western blot, and immunocytochemistry were used to identify cell differentiation and expression of dopaminergic neuron-specific genes in vitro. Behavioral tests including rotational behavior and MWM training tests were also performed to assess the recovery. Our results indicated that combined treatment of CM and neural stem cell transplantation can significantly reduce apomorphine-induced rotational asymmetry and improve spatial learning ability. The CM-NSCs were able to differentiate into dopaminergic neurons in the ventral tegmental area (VTA) and medial forebrain bundle (MFB), and migrated around the lesion site. They showed a higher activity than untreated NSCs in cell survival, migration, and behavior improvement in the dopa-deficit rat model. These findings suggest that the neural stem cells treated with conditioned medium possess a great potential as a graft candidate for the treatment of Parkinson's disease. PMID:26607204

  13. One-step derivation of mesenchymal stem cell (MSC-like cells from human pluripotent stem cells on a fibrillar collagen coating.

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    Yongxing Liu

    Full Text Available Controlled differentiation of human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs into cells that resemble adult mesenchymal stem cells (MSCs is an attractive approach to obtain a readily available source of progenitor cells for tissue engineering. The present study reports a new method to rapidly derive MSC-like cells from hESCs and hiPSCs, in one step, based on culturing the cells on thin, fibrillar, type I collagen coatings that mimic the structure of physiological collagen. Human H9 ESCs and HDFa-YK26 iPSCs were singly dissociated in the presence of ROCK inhibitor Y-27632, plated onto fibrillar collagen coated plates and cultured in alpha minimum essential medium (alpha-MEM supplemented with 10% fetal bovine serum, 50 uM magnesium L-ascorbic acid phosphate and 100 nM dexamethasone. While fewer cells attached on the collagen surface initially than standard tissue culture plastic, after culturing for 10 days, resilient colonies of homogenous spindle-shaped cells were obtained. Flow cytometric analysis showed that a high percentage of the derived cells expressed typical MSC surface markers including CD73, CD90, CD105, CD146 and CD166 and were negative as expected for hematopoietic markers CD34 and CD45. The MSC-like cells derived from pluripotent cells were successfully differentiated in vitro into three different lineages: osteogenic, chondrogenic, and adipogenic. Both H9 hES and YK26 iPS cells displayed similar morphological changes during the derivation process and yielded MSC-like cells with similar properties. In conclusion, this study demonstrates that bioimimetic, fibrillar, type I collagen coatings applied to cell culture plates can be used to guide a rapid, efficient derivation of MSC-like cells from both human ES and iPS cells.

  14. The histopathology of a human mesenchymal stem cell experimental tumor model: support for an hMSC origin for Ewing's sarcoma?

    DEFF Research Database (Denmark)

    Burns, J S; Abdallah, B M; Schrøder, Henrik Daa;

    2008-01-01

    -forming potential of early passage hMSC-TERT20 cells, tumors derived from late passage cells expressed early biomarkers of osteogenesis. However, hMSC-TERT20 cells were heterogeneous for alpha smooth muscle actin (ASMA) expression and one out of six hMSC-TERT20 derived single cell clones was strongly ASMA positive....... Tumors from this ASMA+ clone had distinctive vascular qualities with hot spots of high CD34+ murine endothelial cell density, together with CD34- regions with a branching periodic acid Schiff reaction pattern. Such clone-specific differences in host vascular response provide novel models to explore...

  15. Effects of quercetin, a natural phenolic compound, in the differentiation of human mesenchymal stem cells (MSC) into adipocytes and osteoblasts.

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    Casado-Díaz, Antonio; Anter, Jaouad; Dorado, Gabriel; Quesada-Gómez, José Manuel

    2016-06-01

    Natural phenols may have beneficial properties against oxidative stress, which is associated with aging and major chronic aging-related diseases, such as loss of bone mineral mass (osteoporosis) and diabetes. The main aim of this study was to analyze the effect of quercetin, a major nutraceutical compound present in the "Mediterranean diet", on mesenchymal stem-cell (MSC) differentiation. Such cells were induced to differentiate into osteoblasts or adipocytes in the presence of two quercetin concentrations (0.1 and 10μM). Several physiological parameters and the expression of osteoblastogenesis and adipogenesis marker genes were monitored. Quercetin (10μM) inhibited cell proliferation, alkaline phosphatase (ALPL) activity and mineralization, down-regulating the expression of ALPL, collagen type I alpha 1 (COL1A1) and osteocalcin [bone gamma-carboxyglutamate protein (BGLAP)] osteoblastogenesis-related genes in MSC differentiating into osteoblasts. Moreover, in these cultures, CCAAT/enhancer-binding protein alpha (CEBPA) and peroxisome proliferator-activated receptor gamma 2 (PPARG2) adipogenic genes were induced, and cells differentiated into adipocytes were observed. Quercetin did not affect proliferation, but increased adipogenesis, mainly at 10-μM concentration in MSC induced to differentiate to adipocytes. β- and γ-catenin (plakoglobin) nuclear levels were reduced and increased, respectively, in quercetin-treated cultures. This suggests that the effect of high concentration of quercetin on MSC osteoblastic and adipogenic differentiation is mediated via Wnt/β-catenin inhibition. In conclusion, quercetin supplementation inhibited osteoblastic differentiation and promoted adipogenesis at the highest tested concentration. Such possible adverse effects of high quercetin concentrations should be taken into account in nutraceutical or pharmaceutical strategies using such flavonol. PMID:27142748

  16. Cell therapy medicinal product regulatory framework in Europe and its application for MSC-based therapy development.

    Science.gov (United States)

    Ancans, Janis

    2012-01-01

    Advanced therapy medicinal products (ATMPs), including cell therapy products, form a new class of medicines in the European Union. Since the ATMPs are at the forefront of scientific innovation in medicine, specific regulatory framework has been developed for these medicines and implemented from 2009. The Committee for Advanced Therapies (CAT) has been established at the European Medicines Agency (EMA) for centralized classification, certification and evaluation procedures, and other ATMP-related tasks. Guidance documents, initiatives, and interaction platforms are available to make the new framework more accessible for small- and medium-sized enterprises, academia, hospitals, and foundations. Good understanding of the centralized and national components of the regulatory system is required to plan product development. It is in the best interests of the cell therapy developers to utilize the resources provided starting with the pre-clinical stage. Whilst there have been no mesenchymal stem cell (MSC)-based medicine authorizations in the EU, three MSC products have received marketing approval in other regions since 2011. The information provided on the regulatory requirements, procedures, and initiatives is aimed at facilitating MSC-based medicinal product development and authorization in the EU.

  17. Treatment of radio-induced colorectal lesions with Mesenchymal Stromal Cells (MSC): part of the inflammatory process

    International Nuclear Information System (INIS)

    Throughout the last decades, radiotherapy established as a major tool in the treatment of abdomino-pelvic cancers. Despite great technological evolutions, radiotherapy remains associated with side effects that can sometimes be really harmful, this being mainly due to the toxicity of ionizing radiations for healthy tissues surrounding the tumor. As part of abdomino-pelvic radio-therapies, these side effects mainly affect the gastrointestinal tract, which is very sensitive to radiations. The development of curative treatments thus became a priority. Mesenchymal stem cells (MSC) showed their immunomodulatory ability as well as their ability to regenerate tissue in many models. During my thesis, we aimed at giving rise to the therapeutic advantage brought by MSC in the treatment of radioinduced damage as well as the underlying molecular mechanisms. Our results allowed us to demonstrate the efficiency of our treatment with an effect both on the colic epithelial structure and on its contractile functions. We demonstrated that this therapeutical efficiency depends on two processes. Stimulation of the epithelial proliferation through the Wnt pathway allows the epithelial regeneration process to be enhanced. The increased local corticosterone secretion allows the number and the activation state of T lymphocytes to diminish. Our results moreover suggest the existence of a link between the two observed phenomenons thus providing with a new proof of the combinatory effects of MSC therapy. (author)

  18. Stem cells: A new paradigm

    OpenAIRE

    Kumar Sachin; Singh N

    2006-01-01

    Stem cell therapy is emerging as a potentially revolutionary new way to treat disease and injury, with wide-ranging medical benefits. It aims to repair damaged and diseased body-parts with healthy new cells provided by stem cell transplants. Disease and disorders with no therapies or at best, partially effective ones, are the lure of the pursuit of stem cell research. Recently a plethora of work has been done in this field in world around including India. However, Stem cell research presents ...

  19. Life behind cell walls: paradigm lost, paradigm regained.

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    Lamport, D T

    2001-09-01

    This review of the living cell wall and its protein components is in two parts. The first is anecdotal. A personal account spanning over 40 years research may perhaps be an antidote to one stereotypical view of scientists as detached and humorless. The second part deals with the meaning of function, particularly as it applies to hydroxyproline-rich glycoproteins. Function is a difficult word to define objectively. However, with help from such luminaries as Humpty Dumpty: "A word means what I want it to mean, neither more nor less," and Wittgenstein: "Giving examples of usage ... is the only way to talk about meaning," it is possible to construct a ziggurat representing increasingly complex levels of organization from molecular structure to ecology. Forty years ago I suggested that hydroxyproline-rich structural proteins played a key role in cell wall functioning. But because the bulk of the wall is carbohydrate, there has been an understandable resistance to paradigm change. Expansins, paradoxically, contribute greatly to this resistance because their modus operandi as cell-wall-loosening proteins is based on the idea that they break hydrogen bonds between polysaccharide chains allowing slippage. However, this view is not consistent with the recent discovery [Grobe et al. (1999) Eur. J. Biochem 263: 33-40] that beta-expansins may be proteases, as it implies that the extensin network is not a straightjacket but a substrate for expansin in muro. Such a direct role for extensins in both negative and positive regulation of cell expansion and elongation may constitute a major morphogenetic mechanism operating at all levels of plant growth and development.

  20. Therapeutic potential of mesenchymal stromal cells and MSC conditioned medium in Amyotrophic Lateral Sclerosis (ALS--in vitro evidence from primary motor neuron cultures, NSC-34 cells, astrocytes and microglia.

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    Hui Sun

    Full Text Available Administration of mesenchymal stromal cells (MSC improves functional outcome in the SOD1G93A mouse model of the degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS as well as in models of other neurological disorders. We have now investigated the effect of the interaction between MSC and motor neurons (derived from both non-transgenic and mutant SOD1G93A transgenic mice, NSC-34 cells and glial cells (astrocytes, microglia (derived again from both non-transgenic and mutant SOD1G93A ALS transgenic mice in vitro. In primary motor neurons, NSC-34 cells and astrocytes, MSC conditioned medium (MSC CM attenuated staurosporine (STS - induced apoptosis in a concentration-dependent manner. Studying MSC CM-induced expression of neurotrophic factors in astrocytes and NSC-34 cells, we found that glial cell line-derived neurotrophic factor (GDNF and ciliary neurotrophic factor (CNTF gene expression in astrocytes were significantly enhanced by MSC CM, with differential responses of non-transgenic and mutant astrocytes. Expression of Vascular Endothelial Growth Factor (VEGF in NSC-34 cells was significantly upregulated upon MSC CM-treatment. MSC CM significantly reduced the expression of the cytokines TNFα and IL-6 and iNOS both in transgenic and non-transgenic astrocytes. Gene expression of the neuroprotective chemokine Fractalkine (CX3CL1 was also upregulated in mutant SOD1G93A transgenic astrocytes by MSC CM treatment. Correspondingly, MSC CM increased the respective receptor, CX3CR1, in mutant SOD1G93A transgenic microglia. Our data demonstrate that MSC modulate motor neuronal and glial response to apoptosis and inflammation. MSC therefore represent an interesting candidate for further preclinical and clinical evaluation in ALS.

  1. Cellular Kinetics of Perivascular MSC Precursors

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    William C. W. Chen

    2013-01-01

    Full Text Available Mesenchymal stem/stromal cells (MSCs and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.

  2. Quantification of Mesenchymal Stem Cell (MSC delivery to a target site using in vivo confocal microscopy.

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    Luke J Mortensen

    Full Text Available The ability to deliver cells to appropriate target tissues is a prerequisite for successful cell-based therapy. To optimize cell therapy it is therefore necessary to develop a robust method of in vivo cell delivery quantification. Here we examine Mesenchymal Stem Cells (MSCs labeled with a series of 4 membrane dyes from which we select the optimal dye combination for pair-wise comparisons of delivery to inflamed tissue in the mouse ear using confocal fluorescence imaging. The use of an optimized dye pair for simultaneous tracking of two cell populations in the same animal enables quantification of a test population that is referenced to an internal control population, thereby eliminating intra-subject variations and variations in injected cell numbers. Consistent results were obtained even when the administered cell number varied by more than an order of magnitude, demonstrating an ability to neutralize one of the largest sources of in vivo experimental error and to greatly reduce the number of cells required to evaluate cell delivery. With this method, we are able to show a small but significant increase in the delivery of cytokine pre-treated MSCs (TNF-α & IFN-γ compared to control MSCs. Our results suggest future directions for screening cell strategies using our in vivo cell delivery assay, which may be useful to develop methods to maximize cell therapeutic potential.

  3. Effect of mesenchymal stromal cells (MSC) on chronic visceral hypersensitivity in a radio-induced colonic ulceration model in the rat

    International Nuclear Information System (INIS)

    Patients who undergo pelvic radiotherapy may develop significant incidence of undesirable chronic gastrointestinal complications resulting from radiation-induced damages around the tumour. Chronic visceral pain is one of the radiation-induced side effects that greatly affects the quality of life of 'cancer survivors'. The lack of effective analgesic treatment highlights the importance of novel and effective therapeutic strategies. In our laboratory, mesenchymal stromal cell (MSC) based approach showed beneficial immunomodulatory and regenerative effects in a rat model of irreversible radiationinduced colonic ulcers. The goal of my work was to assess the relevance of this model to study radiation-induced visceral persistent hypersensitivity and its modulation by MSC treatment. We first demonstrated that this model is associated with long-lasting visceral hypersensitivity and central neuronal sensitization. In this context we showed then that mast cells (MC) are involved in the mechanism of peripheral sensitization. Moreover, we suggested the implication of the neuro-mediator NO. in the pathophysiology of persistent radiation-induced visceral hypersensitivity. We also suggested that MSC treatment reversed radiation-induced hypersensitivity by a mechanism that in part may involve the modulation of MC activation and/or the decrease in the number of MC and nerve fiber interactions. In addition, MSC treatment reduced the percentage of nitrinergic neurons, increased after irradiation, and restored colonic muscular contractibility. Such processes may promote the therapeutic benefit of MSC observed in our study. In conclusion, this work provided new insights on the therapeutic benefit of MSC in our study model and a new argument in favour of their use in a future clinical trial to cure abdomino-pelvic radiotherapy side effects. (author)

  4. Cytoplasmic Domain of MscS Interacts with Cell Division Protein FtsZ: A Possible Non-Channel Function of the Mechanosensitive Channel in Escherichia Coli.

    Directory of Open Access Journals (Sweden)

    Piotr Koprowski

    Full Text Available Bacterial mechano-sensitive (MS channels reside in the inner membrane and are considered to act as emergency valves whose role is to lower cell turgor when bacteria enter hypo-osmotic environments. However, there is emerging evidence that members of the Mechano-sensitive channel Small (MscS family play additional roles in bacterial and plant cell physiology. MscS has a large cytoplasmic C-terminal region that changes its shape upon activation and inactivation of the channel. Our pull-down and co-sedimentation assays show that this domain interacts with FtsZ, a bacterial tubulin-like protein. We identify point mutations in the MscS C-terminal domain that reduce binding to FtsZ and show that bacteria expressing these mutants are compromised in growth on sublethal concentrations of β-lactam antibiotics. Our results suggest that interaction between MscS and FtsZ could occur upon inactivation and/or opening of the channel and could be important for the bacterial cell response against sustained stress upon stationary phase and in the presence of β-lactam antibiotics.

  5. Adult Cardiac-Resident MSC-like Stem Cells with a Proepicardial Origin

    NARCIS (Netherlands)

    Chong, James J. H.; Chandrakanthan, Vashe; Xaymardan, Munira; Asli, Naisana S.; Li, Joan; Ahmed, Ishtiaq; Heffernan, Corey; Menon, Mary K.; Scarlett, Christopher J.; Rashidianfar, Amirsalar; Biben, Christine; Zoellner, Hans; Colvin, Emily K.; Pimanda, John E.; Biankin, Andrew V.; Zhou, Bin; Pu, William T.; Prall, Owen W. J.; Harvey, Richard P.

    2011-01-01

    Colony-forming units fibroblast (CFU-Fs), analogous to those giving rise to bone marrow (BM) mesenchymal stem cells (MSCs), are present in many organs, although the relationship between BM and organ-specific CFU-Fs in homeostasis and tissue repair is unknown. Here we describe a population of adult c

  6. Tumor Stroma Manipulation By MSC.

    Science.gov (United States)

    Grisendi, Giulia; Spano, Carlotta; Rossignoli, Filippo; D Souza, Naomi; Golinelli, Giulia; Fiori, Agnese; Horwitz, Edwin M; Guarneri, Valentina; Piacentini, Federico; Paolucci, Paolo; Dominici, Massimo

    2016-01-01

    Tumor stroma (TS) plays relevant roles in all steps of cancer development. We here address several fundamental aspects related with the interaction between cancer cells and their stromal counterparts. Dissecting these players is of pivotal importance to understand oncogenesis, immunoescape and drug resistance. In addition, this better comprehension will allow the introduction of novel and more effective therapeutic approaches where manipulated stromal elements may become detrimental for tumor growth. Our group and others rely on the use of multipotent mesenchymal stromal/stem cells (MSC) as anti-cancer tools, since these putative TS cell precursors can deliver potent apoptosis-inducing agents. Multimodal-armed MSC can target a variety of cancers in vitro and, when injected in vivo, they localize into tumors mediating cell death without evident toxicities to normal tissues. While several aspects of these strategies shall require further investigations, these approaches collectively indicate how TS manipulation by MSC represents a tool to influence the fate of cancer cells, creating a new generation of anti-cancer strategies. PMID:26953248

  7. A critical role of IFNγ in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Bone-marrow-derived mesenchymal stem cells (MSCs) have been shown to possess immunosuppressive properties, e.g., by inhibiting T cell proliferation. Activated T cells can also enhance the immunosuppression ability of MSCs. The precise mechanisms underlying MSC-mediated immunosuppression remain largely undefined, although both cell-cell contact and soluble factors have been implicated; nor is it clear how the immunosuppressive property of MSCs is modulated by T cells. Using MSCs isolated from mouse bone marrow, we show here that interferon gamma (IFNγ), a well-known proinflammatory cytokine produced by activated T cells, plays an important role in priming the immunosuppressive property of MSCs. Mechanistically, IFNγ acts directly on MSCs and leads to up-regulation of B7-H1, an inhibitory surface molecule in these stem cells. MSCs primed by activated T cells derived from IFNγ-/- mouse exhibited dramatically reduced ability to suppress T cell proliferation, a defect that can be rescued by supplying exogenous IFNy. Moreover, siRNA-mediated knockdown of B7-H1 in MSCs abolished immunosuppression by these cells. Taken together, our results suggest that IFNy plays a critical role in triggering the immunosuppresion by MSCs through upregulating B7-H1 in these cells, and provide evidence supporting the cell-cell contact mechanism in MSC-mediated immunosuppression.

  8. Deep tissue single cell MSC ablation using a fiber laser source to evaluate therapeutic potential in osteogenesis imperfecta

    Science.gov (United States)

    Tehrani, Kayvan F.; Pendleton, Emily G.; Lin, Charles P.; Mortensen, Luke J.

    2016-04-01

    Osteogenesis imperfecta (OI) is a currently uncurable disease where a mutation in collagen type I yields brittle bones. One potential therapy is transplantation of mesenchymal stem cells (MSCs), but controlling and enhancing transplanted cell survival has proven challenging. Therefore, we use a 2- photon imaging system to study individual transplanted cells in the living bone marrow. We ablated cells deep in the bone marrow and observed minimal collateral damage to surrounding tissue. Future work will evaluate the local impact of transplanted MSCs on bone deposition in vivo.

  9. Therapeutic use of human mesenchymal stem cells (MSC) for the treatment of radio-induced diseases; Utilisation des Cellules Souches Mesenchymateuses humaines dans le traitement des atteintes tissulaires radio-induites

    Energy Technology Data Exchange (ETDEWEB)

    Mouiseddine, Moubarak

    2008-05-15

    Ionising radiation can induce toxic effects on body. They provoke physiological modifications of tissues and organs which can be lethal. Total body irradiation or local abdominal irradiation can induce serious complications. Intestine is the first tissue concerned by these side effects. Radiation induces malabsorption of the intestine and lost of it integrity. Radio-induced physiopathological effects on intestine could lead to distant effects on other tissues and organs such as liver. The actual treatments have a limited efficiency or are not adapted to gastrointestinal damages. Indeed, in this type of lesions, the heterogeneous systems which are concerned and the gravity of lesions complicates the medical care. Our purpose is to show that cell therapy using human mesenchymal stem cells (MSC) constitutes resolution in this type of illness. The works which are presented in this thesis show that MSC are multi-potent and have heterogeneous expression of molecules. These cells are able to establish themselves in many organs and tissues after injection into irradiated body. Thus we have shown that MSC can prevent the small intestine from radio-induced damages. Indeed we demonstrate that through their actions on gut, MSC can indirectly restore hepatic integrity. (author)

  10. Characterization of normal and cancer stem cells: One experimental paradigm for two kinds of stem cells

    OpenAIRE

    Mayol, Jean-François; Loeuillet, Corinne; Hérodin, Francis; Wion, Didier

    2009-01-01

    The characterization of normal stem cells and cancer stem cells uses the same paradigm. These cells are isolated by a Fluorescent-Activated Cell Sorting step and their stemness is assayed following implantation into animals. However, differences exist between these two kinds of stem cells. Therefore, the translation of the experimental procedures used for normal stem cell isolation into the cancer stem cell research field is a potential source of artefacts. In addition, normal stem cell thera...

  11. Protein Localization in Escherichia coli Cells: Comparison of the Cytoplasmic Membrane Proteins ProP, LacY, ProW, AqpZ, MscS, and MscL

    OpenAIRE

    Romantsov, Tatyana; Battle, Andrew R.; Hendel, Jenifer L.; Martinac, Boris; Wood, Janet M.

    2010-01-01

    Fluorescence microscopy has revealed that the phospholipid cardiolipin (CL) and FlAsH-labeled transporters ProP and LacY are concentrated at the poles of Escherichia coli cells. The proportion of CL among E. coli phospholipids can be varied in vivo as it is decreased by cls mutations and it increases with the osmolality of the growth medium. In this report we compare the localization of CL, ProP, and LacY with that of other cytoplasmic membrane proteins. The proportion of cells in which FlAsH...

  12. Checking MSC Specifications for Timing Inconsistency

    Institute of Scientific and Technical Information of China (English)

    LI Xuandong(李宣东); TAN Wenkai(谭文凯); ZHENG Guoliang(郑国梁)

    2002-01-01

    Message sequence chart (MSC) is a graphical and textual language for the description and specification of the interactions between system components. MSC specifica tions allow convenient expression of multiple scenarios, and offer an intuitive and visual way of describing design requirements. Like any other aspect of the specification and design process, MSCs are amenable to errors, and their analysis is important. In this paper, the verification problem of MSC specification for timing inconsistency is studied, which means that no execu tion scenario described by an MSC specification is timing consistent. An algorithm is developed to check MSC specifications for timing inconsistency.

  13. Hungarian medical physics MSc education

    International Nuclear Information System (INIS)

    The medical physics specialisation aims at providing high level interdisciplinary theoretical and practical knowledge and readily applicable skills, which can put into action in both the clinical and the R and D field. The first competence based gradual medical physics course in the B.Sc./M.Sc. system in Hungary was launched two years ago at the Faculty of Natural Sciences of Budapest University of Technology and Economics managed by the Institute of Nuclear Techniques. The MSc programme was compiled on the base of EFOMP, IPEM, AAPM and IAEA recommendations. The course curriculum comprises fundamental physical subjects (atomic and molecular physics, nuclear physics and particle physics) as well as fundamental medical knowledge (anatomy, physiology and radiobiology) required for subjects of diagnostic and therapy. Students of this MSc branch may chose further subjects from a 'compulsory optional' set of subjects, which contains medical imaging, X-ray diagnostics, radiation therapy, magnetic resonance imaging, radiation protection, Monte Carlo calculation and its clinical applications, ultrasound diagnostics and nuclear medicine. (authors)

  14. GMP-compliant isolation and large-scale expansion of bone marrow-derived MSC.

    Directory of Open Access Journals (Sweden)

    Natalie Fekete

    Full Text Available BACKGROUND: Mesenchymal stromal cells (MSC have gained importance in tissue repair, tissue engineering and in immunosupressive therapy during the last years. Due to the limited availability of MSC in the bone marrow, ex vivo amplification prior to clinical application is requisite to obtain therapeutic applicable cell doses. Translation of preclinical into clinical-grade large-scale MSC expansion necessitates precise definition and standardization of all procedural parameters including cell seeding density, culture medium and cultivation devices. While xenogeneic additives such as fetal calf serum are still widely used for cell culture, its use in the clinical context is associated with many risks, such as prion and viral transmission or adverse immunological reactions against xenogeneic components. METHODS AND FINDINGS: We established animal-free expansion protocols using platelet lysate as medium supplement and thereby could confirm its safety and feasibility for large-scale MSC isolation and expansion. Five different GMP-compliant standardized protocols designed for the safe, reliable, efficient and economical isolation and expansion of MSC was performed and MSC obtained were analyzed for differentiation capacity by qPCR and histochemistry. Expression of standard MSC markers as defined by the International Society for Cellular Therapy as well as expression of additional MSC markers and of various chemokine and cytokine receptors was analysed by flow cytometry. Changes of metabolic markers and cytokines in the medium were addressed using the LUMINEX platform. CONCLUSIONS: The five different systems for isolation and expansion of MSC described in this study are all suitable to produce at least 100 millions of MSC, which is commonly regarded as a single clinical dose. Final products are equal according to the minimal criteria for MSC defined by the ISCT. We showed that chemokine and integrin receptors analyzed had the same expression pattern

  15. Co-cultivation of keratinocyte-human mesenchymal stem cell (hMSC) on sericin loaded electrospun nanofibrous composite scaffold (cationic gelatin/hyaluronan/chondroitin sulfate) stimulates epithelial differentiation in hMSCs: In vitro study.

    Science.gov (United States)

    Bhowmick, Sirsendu; Scharnweber, Dieter; Koul, Veena

    2016-05-01

    Fortifying the scaffold with bioactive molecules and glycosaminoglycans (GAGs), is an efficient way to design new generation tissue engineered biomaterials. In this study, we evaluated the synergistic effect of electrospun nanofibrous composite scaffold (cationic gelatin/hyaluronan/chondroitin sulfate) loaded with sericin and, contact co-culture of human mesenchymal stem cells (hMSCs)-keratinocytes on hMSCs' differentiation towards epithelial lineage. Cationic gelatin is prepared with one step novel synthesis process by grafting quaternary ammonium salts to the backbone of gelatin. Release kinetics studies showed that Fickian diffusion is the major release mechanism for both GAGs and sericin/gelatin. In vitro biocompatibility of the electrospun scaffold was evaluated in terms of LDH and DNA quantification assay on human foreskin fibroblast, human keratinocyte and hMSC. Significant proliferation (∼ 4-6 fold) was detected after culturing all three cell on the electrospun scaffold containing sericin. After 5 days of contact co-culture, results revealed that electrospun scaffold containing sericin promote epithelial differentiation of hMSC in terms of several protein markers (keratin 14, ΔNp63α and Pan-cytokeratin) and gene expression of some dermal proteins (keratin 14, ΔNp63α). Findings of this study will foster the progress of current skin tissue engineering scaffolds by understanding the skin regeneration and wound healing process. PMID:26946262

  16. Expansion and Harvesting of hMSC-TERT

    DEFF Research Database (Denmark)

    Weber, Christian; Pohl, Sebastian; Pörtner, Ralf;

    2007-01-01

    cultivation and harvesting. Nonporous microcarriers are preferable when the cells need to be kept in viable condition for further applications like tissue engineering or cell therapy. In this study, the qualification of Biosilon, Cytodex 1, Cytodex 3, RapidCell and P102-L for expansion of h......MSC-TERT with an associated harvesting process using either trypsin, accutase, collagenase or a trypsin-accutase mixture was investigated. A subsequent adipogenic differentiation of harvested hMSC-TERT was performed in order to observe possible negative effects on their (adipogenic) differentiation potential as a result...... of the cultivation and harvesting method. The cultivated cells showed an average growth rate of 0.52 d(-1). The cells cultivated on Biosilon, RapidCell and P102-L were harvested succesfully achieving high cell yield and vitalities near 100%. This was not the case for cells on Cytodex 1 and Cytodex 3. The trypsin...

  17. Differentiation of hMSC in Micromass Culture

    Institute of Scientific and Technical Information of China (English)

    Natalia; De; ISIA; Céline; HUSELSTEIN; Luc; MARCHAL; Marie-Nathalie; SARDA-KOLOPP; Jing-Ping; OU; YANG; Jean-Franois; STOLTZ; Assia; ELJAAFARI

    2005-01-01

    1 Introduction Mesenchymal stem cells (MSCs) are multipotential stem cells which can be expanded in culture while still maintaining their undifferentiated state. They have the potential to differentiate into distinct mesenchymal tissue cells, including chondrocytes. Thus, they are an attractive cell source for cartilage tissue engineering. In vitro high density micromass culture has been widely used for chondrogenesis induction. The objective of our study was to analyze viability and differentiation of hMSC...

  18. Stem cells: A new paradigm in periodontal regeneration

    Directory of Open Access Journals (Sweden)

    Marawar Pramod P, Shinde Sagar K, Mani Ameet M, Patil Ishwardas D

    2013-04-01

    Full Text Available Stem cells are a unique type of cell that forms the basis of the development, growth and survival of a living organism. Though the term is often used to describe controversial embryonic stem cells, there are many different types of stem cells, classified by their original location and/or method of formation. Stem cells are undifferentiated cells that go on developing into any of more than 200 type of cells that adult Human body hold. Now a days stem cells have significant use in regenerative periodontal therapy. Recently, reports have begun to emerge demonstrating that populations of adult stem cells reside in the periodontal ligament of humans and other animals. This opens the way for new cell-based therapies for periodontal regeneration.This review provides an overview of adult human stem cells and their potential use in periodontal regeneration.

  19. Different Culture Media Affect Proliferation, Surface Epitope Expression, and Differentiation of Ovine MSC.

    Science.gov (United States)

    Adamzyk, Carina; Emonds, Tanja; Falkenstein, Julia; Tolba, René; Jahnen-Dechent, Wilhelm; Lethaus, Bernd; Neuss, Sabine

    2013-01-01

    Orthopedic implants including engineered bone tissue are commonly tested in sheep. To avoid rejection of heterologous or xenogeneic cells, autologous cells are preferably used, that is, ovine mesenchymal stem cells (oMSC). Unlike human MSC, ovine MSC are not well studied regarding isolation, expansion, and characterization. Here we investigated the impact of culture media composition on growth characteristics, differentiation, and surface antigen expression of oMSC. The culture media varied in fetal calf serum (FCS) content and in the addition of supplements and/or additional epidermal growth factor (EGF). We found that FCS strongly influenced oMSC proliferation and that specific combinations of supplemental factors (MCDB-201, ITS-plus, dexamethasone, and L-ascorbic acid) determined the expression of surface epitopes. We compared two published protocols for oMSC differentiation towards the osteogenic, adipogenic, and chondrogenic fate and found (i) considerable donor to donor variations, (ii) protocol-dependent variations, and (iii) variations resulting from the preculture medium composition. Our results indicate that the isolation and culture of oMSC in different growth media are highly variable regarding oMSC phenotype and behaviour. Furthermore, variations from donor to donor critically influence growth rate, surface marker expression, and differentiation.

  20. Regenerative Endodontics in light of the stem cell paradigm

    OpenAIRE

    ROSA, Vinicius; Botero, Tatiana M.; Jacques E. Nör

    2011-01-01

    Stem cells play a critical role in development and in tissue regeneration. The dental pulp contains a small sub-population of stem cells that are involved in the response of the pulp to caries progression. Specifically, stem cells replace odontoblasts that have undergone cell death as a consequence of the cariogenic challenge. Stem cells also secrete factors that have the potential to enhance pulp vascularization and provide the oxygen and nutrients required for the dentinogenic response that...

  1. EMT and MET as paradigms for cell fate switching

    Institute of Scientific and Technical Information of China (English)

    Jiekai Chen; Qingkai Han; Duanqing Pei

    2012-01-01

    Cell fate determination is a major unsolved problem in cell and developmental biology,The discovery of reprogramming by pluripotent factors offers a rational system to investigate the molecular mechanisms associated with cell fate decisions.The idea that reprogramming of fibroblasts starts with a mesenchymal-epithelial transition (MET) suggests that the process is perhaps a reversal of epithelial to mesenchymal transition (EMT) found frequently during early embryogenesis,As such,we believe that investigations into MET-EMT may yield detailed molecular insights into cell fate decisions,not only for the switching between epithelial and mesenchymal cells,but also other cell types.

  2. Msc1 acts through histone H2A.Z to promote chromosome stability in Schizosaccharomyces pombe.

    Science.gov (United States)

    Ahmed, Shakil; Dul, Barbara; Qiu, Xinxing; Walworth, Nancy C

    2007-11-01

    As a central component of the DNA damage checkpoint pathway, the conserved protein kinase Chk1 mediates cell cycle progression when DNA damage is generated. Msc1 was identified as a multicopy suppressor capable of facilitating survival in response to DNA damage of cells mutant for chk1. We demonstrate that loss of msc1 function results in an increased rate of chromosome loss and that an msc1 null allele exhibits genetic interactions with mutants in key kinetochore components. Multicopy expression of msc1 robustly suppresses a temperature-sensitive mutant (cnp1-1) in the centromere-specific histone H3 variant CENP-A, and localization of CENP-A to the centromere is compromised in msc1 null cells. We present several lines of evidence to suggest that Msc1 carries out its function through the histone H2A variant H2A.Z, encoded by pht1 in fission yeast. Like an msc1 mutant, a pht1 mutant also exhibits chromosome instability and genetic interactions with kinetochore mutants. Suppression of cnp1-1 by multicopy msc1 requires pht1. Likewise, suppression of the DNA damage sensitivity of a chk1 mutant by multicopy msc1 also requires pht1. We present the first genetic evidence that histone H2A.Z may participate in centromere function in fission yeast and propose that Msc1 acts through H2A.Z to promote chromosome stability and cell survival following DNA damage. PMID:17947424

  3. Aging of perennial cells and organ parts according to the programmed aging paradigm.

    Science.gov (United States)

    Libertini, Giacinto; Ferrara, Nicola

    2016-04-01

    If aging is a physiological phenomenon-as maintained by the programmed aging paradigm-it must be caused by specific genetically determined and regulated mechanisms, which must be confirmed by evidence. Within the programmed aging paradigm, a complete proposal starts from the observation that cells, tissues, and organs show continuous turnover: As telomere shortening determines both limits to cell replication and a progressive impairment of cellular functions, a progressive decline in age-related fitness decline (i.e., aging) is a clear consequence. Against this hypothesis, a critic might argue that there are cells (most types of neurons) and organ parts (crystalline core and tooth enamel) that have no turnover and are subject to wear or manifest alterations similar to those of cells with turnover. In this review, it is shown how cell types without turnover appear to be strictly dependent on cells subjected to turnover. The loss or weakening of the functions fulfilled by these cells with turnover, due to telomere shortening and turnover slowing, compromises the vitality of the served cells without turnover. This determines well-known clinical manifestations, which in their early forms are described as distinct diseases (e.g., Alzheimer's disease, Parkinson's disease, age-related macular degeneration, etc.). Moreover, for the two organ parts (crystalline core and tooth enamel) without viable cells or any cell turnover, it is discussed how this is entirely compatible with the programmed aging paradigm.

  4. Msc1 Acts Through Histone H2A.Z to Promote Chromosome Stability in Schizosaccharomyces pombe

    OpenAIRE

    Ahmed, Shakil; Dul, Barbara; Qiu, Xinxing; Walworth, Nancy C.

    2007-01-01

    As a central component of the DNA damage checkpoint pathway, the conserved protein kinase Chk1 mediates cell cycle progression when DNA damage is generated. Msc1 was identified as a multicopy suppressor capable of facilitating survival in response to DNA damage of cells mutant for chk1. We demonstrate that loss of msc1 function results in an increased rate of chromosome loss and that an msc1 null allele exhibits genetic interactions with mutants in key kinetochore components. Multicopy expres...

  5. TOR and paradigm change: cell growth is controlled.

    Science.gov (United States)

    Hall, Michael N

    2016-09-15

    This year marks the 25th anniversary of the discovery of target of rapamycin (TOR), a highly conserved kinase and central controller of cell growth. In this Retrospective, I briefly describe the discovery of TOR and the subsequent elucidation of its cellular role. I place particular emphasis on an article by Barbet et al. from 1996, the first suggesting that TOR controls cell growth in response to nutrients.

  6. TOR and paradigm change: cell growth is controlled.

    Science.gov (United States)

    Hall, Michael N

    2016-09-15

    This year marks the 25th anniversary of the discovery of target of rapamycin (TOR), a highly conserved kinase and central controller of cell growth. In this Retrospective, I briefly describe the discovery of TOR and the subsequent elucidation of its cellular role. I place particular emphasis on an article by Barbet et al. from 1996, the first suggesting that TOR controls cell growth in response to nutrients. PMID:27634743

  7. USING OF MSC WITH DIFFERENT ONTOGENETIC MATURITY FOR CORRECTION OF CHRONIC FIBROSING LIVER DAMAGE

    Directory of Open Access Journals (Sweden)

    M. Y. Shagidulin

    2013-01-01

    Full Text Available Aim. To compare the effectiveness of MSC with different degree of ontogenetic maturity (MSC bone marrow – MSC BM and MSC umbilical cord – MSC UC on regenerative processes in injured liver. Methods. In 4 groups of experiments on Wistar rats (n = 80 with a model of fibrotic toxic liver damage (FLD it was studied the effect of MSCs with different degree of ontogenetic maturity on recovery processes at the regeneration of damaged liver: 1 gr. – Control, 2 gr. and 3 gr. introduction of MSC BM, included in Sphero®GEL-long in doses of 2.5 ×106 and 5.0 x 106 cells, respectively, and 4 gr. – introduction of MSC UC in the form of cell-spheroids (8–10 × 105 cells. The cells were injected into the damaged liver in 7 days after the end of FDL-modeling. The effect of cell therapy was studied during 180 days. The effectiveness of corrective therapy was evaluated by the results of functional and morphological investigations of livers (histological control of parenchymal and nonparenchy- mal liver tissue. Results. MSC BM in both doses and MSC UC contributed to a more rapid normalization of liver enzyme indices compared with the control (1 gr., but the differences in the rate of recovery of disturbed enzymatic liver functions between groups 2, 3 and 4 – were absent. In 90 days after the cell application it was determined a more pronounced recovery activity of cells in groups 3 and 4; in 180 days the more pronounced activation of recovery processes was observed in group 3; but in group 4 the sclerotic processes were more pro- nounced in this period. Conclusion. For the induction of recovery processes in damage liver it is advisable not to use the MSC UC, but to use MSC BM in the Sphero®GEL, because MSC BM exert not only local but also systemic immune-regulatory effect, increasing the pool of T-reg. cells, which are additional carriers of regenera- tion information in organism. 

  8. The nucleolus: a paradigm for cell proliferation and aging.

    Science.gov (United States)

    Comai, L

    1999-12-01

    The nucleolus is the cellular site of ribosome biosynthesis. At this site, active ribosomal DNA (rDNA) genes are rapidly transcribed by RNA polymerase I (pol I) molecules. Recent advances in our understanding of the pol I transcription system have indicated that regulation of ribosomal RNA (rRNA) synthesis is a critical factor in cell growth. Importantly, the same signaling networks that control cell growth and proliferation and are deregulated in cancer appear to control pol I transcription. Therefore, the study of the biochemical basis for growth regulation of pol I transcription can provide basic information about the nuclear signaling network. Hopefully, this information may facilitate the search for drugs that can inhibit the growth of tumor cells by blocking pol I activation. In addition to its function in ribosome biogenesis, recent studies have revealed the prominent role of the nucleolus in cell senescence. These findings have stimulated a new wave of research on the functional relationship between the nucleolus and aging. The aim of this review is to provide an overview of some current topics in the area of nucleolus biology, and it has been written for a general readership.

  9. The nucleolus: a paradigm for cell proliferation and aging

    Directory of Open Access Journals (Sweden)

    Comai L.

    1999-01-01

    Full Text Available The nucleolus is the cellular site of ribosome biosynthesis. At this site, active ribosomal DNA (rDNA genes are rapidly transcribed by RNA polymerase I (pol I molecules. Recent advances in our understanding of the pol I transcription system have indicated that regulation of ribosomal RNA (rRNA synthesis is a critical factor in cell growth. Importantly, the same signaling networks that control cell growth and proliferation and are deregulated in cancer appear to control pol I transcription. Therefore, the study of the biochemical basis for growth regulation of pol I transcription can provide basic information about the nuclear signaling network. Hopefully, this information may facilitate the search for drugs that can inhibit the growth of tumor cells by blocking pol I activation. In addition to its function in ribosome biogenesis, recent studies have revealed the prominent role of the nucleolus in cell senescence. These findings have stimulated a new wave of research on the functional relationship between the nucleolus and aging. The aim of this review is to provide an overview of some current topics in the area of nucleolus biology, and it has been written for a general readership.

  10. Breaking Out of the Cell: On The Benefits of a New Spreadsheet User-Interaction Paradigm

    CERN Document Server

    Hellman, Ziv

    2008-01-01

    Contemporary spreadsheets are plagued by a profusion of errors, auditing difficulties, lack of uniform development methodologies, and barriers to easy comprehension of the underlying business models they represent. This paper presents a case that most of these difficulties stem from the fact that the standard spreadsheet user-interaction paradigm - the 'cell-matrix' approach - is appropriate for spreadsheet data presentation but has significant drawbacks with respect to spreadsheet creation, maintenance and comprehension when workbooks pass a minimal threshold of complexity. An alternative paradigm for the automated generation of spreadsheets directly from plain-language business model descriptions is presented along with its potential benefits. Sunsight Modeller (TM), a working software system implementing the suggested paradigm, is briefly described.

  11. Chronic exposure of low dose salinomycin inhibits MSC migration capability in vitro

    OpenAIRE

    Scherzad, Agmal; HACKENBERG, STEPHAN; FROELICH, KATRIN; RAK, KRISTEN; HAGEN, RUDOLF; TAEGER, JOHANNES; BREGENZER, MAXIMILLIAN; KLEINSASSER, NORBERT

    2016-01-01

    Salinomycin is a polyether antiprotozoal antibiotic that is used as a food additive, particularly in poultry farming. By consuming animal products, there may be a chronic human exposure to salinomycin. Salinomycin inhibits the differentiation of preadipocytes into adipocytes. As human mesenchymal stem cells (MSC) may differentiate into different mesenchymal cells, it thus appeared worthwhile to investigate whether chronic salinomycin exposure impairs the functional properties of MSC and induc...

  12. New paradigms for metabolic modeling of human cells

    DEFF Research Database (Denmark)

    Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    Abnormalities in cellular functions are associated with the progression of human diseases, often resulting in metabolic reprogramming. GEnome-scale metabolic Models (GEMs) have enabled studying global metabolic reprogramming in connection with disease development in a systematic manner. Here we...... review recent work on reconstruction of GEMs for human cell/tissue types and cancer, and the use of GEMs for identification of metabolic changes occurring in response to disease development. We further discuss how GEMs can be used for the development of efficient therapeutic strategies. Finally...

  13. Finding and tracing human MSC in 3D microenvironments with the photoconvertible protein Dendra2

    Science.gov (United States)

    Caires, Hugo R.; Gomez-Lazaro, Maria; Oliveira, Carla M.; Gomes, David; Mateus, Denisa D.; Oliveira, Carla; Barrias, Cristina C.; Barbosa, Mário A.; Almeida, Catarina R.

    2015-05-01

    Mesenchymal Stem/Stromal Cells (MSC) are a promising cell type for cell-based therapies - from tissue regeneration to treatment of autoimmune diseases - due to their capacity to migrate to damaged tissues, to differentiate in different lineages and to their immunomodulatory and paracrine properties. Here, a simple and reliable imaging technique was developed to study MSC dynamical behavior in natural and bioengineered 3D matrices. Human MSC were transfected to express a fluorescent photoswitchable protein, Dendra2, which was used to highlight and follow the same group of cells for more than seven days, even if removed from the microscope to the incubator. This strategy provided reliable tracking in 3D microenvironments with different properties, including the hydrogels Matrigel and alginate as well as chitosan porous scaffolds. Comparison of cells mobility within matrices with tuned physicochemical properties revealed that MSC embedded in Matrigel migrated 64% more with 5.2 mg protein/mL than with 9.6 mg/mL and that MSC embedded in RGD-alginate migrated 51% faster with 1% polymer concentration than in 2% RGD-alginate. This platform thus provides a straightforward approach to characterize MSC dynamics in 3D and has applications in the field of stem cell biology and for the development of biomaterials for tissue regeneration.

  14. Evaluation of AD-MSC (adipose-derived mesenchymal stem cells) as a vehicle for IFN-β delivery in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Mohammadzadeh, Adel; Pourfathollah, Ali Akbar; Shahrokhi, Somayeh; Fallah, Ali; Tahoori, Mohammad Taher; Amari, Afshin; Forouzandeh, Mahdi; Soleimani, Masoud

    2016-08-01

    Interferon-β (IFN-β) is commonly used as a disease modifying drug for the treatment of relapse-remitting multiple sclerosis (RR-MS). However, the underlying mechanism by which IFN-β mediate this immunosuppressive effect is still unknown. In this study, we analyzed the effects of genetically modified adipose-derived mesenchymal stem cells (AD-MSCs) expressing murine interferon beta (MSCs-VP/IFN-β) on the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Lymph node mononuclear cells and serum were examined by using RT-PCR and ELISA methods to measure the production of IL-10 and IL-17 gene and protein expression, respectively. Our results indicated that in the MSCs-VP/IFN-β treated group induction of Tregs and IL-10 and reduction of IL-17 were significant. Taken together, we showed that using AD-MSCs expressing IFN-β as an anti-inflammatory agent, offer evidence supporting that the stem cell therapies in EAE conceivably will improve the valuable effects of IFN-β in this autoimmune disease. PMID:27373971

  15. Infusion of Trx-1-overexpressing hucMSC prolongs the survival of acutely irradiated NOD/SCID mice by decreasing excessive inflammatory injury.

    Directory of Open Access Journals (Sweden)

    JiangWei Hu

    Full Text Available A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector-mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC assay, a hydrogen peroxide (H2O2 content determination assay in vivo, a H2O2-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC-Trx-1, with hucMSC, and with saline that were exposed to 4.5 Gy (60Co-γ-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin(-CD117(+: hucMSC-Trx-1 vs. hucMSC, P<0.05; hucMSC-Trx-1 vs. NS, P<0.01, promoting the formation of red blood cells and hemoglobin (hucMSC-Trx-1 vs. hucMSC or NS, P<0.05, reducing inflammation and damage in important organs (Bone marrow and lung: hucMSC-Trx-1 vs. NS, P<0.01; hucMSC-Trx-1 vs. hucMSC, P<0.05. Liver and intestine: hucMSC-Trx-1 vs. NS, P<0.05; hucMSC-Trx-1 vs. hucMSC, P<0.05, and prolonging survival (hucMSC-Trx-1 vs. hucMSC or NS, P<0

  16. Marketing: MSc in logistics and transportation

    OpenAIRE

    Jenkins, Mark

    1983-01-01

    The objective of this course is to introduce the basic concepts of marketing to students undertaking an MSc in Transportation and Logistics. This module will take a strategic view of marketing in that it will develop ideas for achieving sustainable competitive advantage.

  17. The c-Met Inhibitor MSC2156119J Effectively Inhibits Tumor Growth in Liver Cancer Models

    Energy Technology Data Exchange (ETDEWEB)

    Bladt, Friedhelm, E-mail: Friedhelm.Bladt@merckgroup.com; Friese-Hamim, Manja; Ihling, Christian; Wilm, Claudia; Blaukat, Andree [EMD Serono, and Merck Serono Research and Development, Merck KGaA, Darmstadt 64293 (Germany)

    2014-08-19

    The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase with hepatocyte growth factor (HGF) as its only high-affinity ligand. Aberrant activation of c-Met is associated with many human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic efficacy of the c-Met inhibitor MSC2156119J (EMD 1214063) in patient-derived tumor explants. BALB/c nude mice were inoculated with MHCC97H cells or with tumor fragments of 10 patient-derived primary liver cancer explants selected according to c-Met/HGF expression levels. MSC2156119J (10, 30, and 100 mg/kg) and sorafenib (50 mg/kg) were administered orally as single-agent treatment or in combination, with vehicle as control. Tumor response, metastases formation, and alpha fetoprotein (AFP) levels were measured. MSC2156119J inhibited tumor growth and induced complete regression in mice bearing subcutaneous and orthotopic MHCC97H tumors. AFP levels were undetectable after 5 weeks of MSC2156119J treatment, and the number of metastatic lung foci was reduced. Primary liver explant models with strong c-Met/HGF activation showed increased responsiveness to MSC2156119J, with MSC2156119J showing similar or superior activity to sorafenib. Tumors characterized by low c-Met expression were less sensitive to MSC2156119J. MSC2156119J was better tolerated than sorafenib, and combination therapy did not improve efficacy. These findings indicate that selective c-Met/HGF inhibition with MSC2156119J is associated with marked regression of c-Met high-expressing tumors, supporting its clinical development as an antitumor treatment for HCC patients with active c-Met signaling.

  18. Sympathetic denervation-induced MSC mobilization in distraction osteogenesis associates with inhibition of MSC migration and osteogenesis by norepinephrine/adrb3.

    Directory of Open Access Journals (Sweden)

    Zhaojie Du

    Full Text Available The sympathetic nervous system regulates bone formation and resorption under physiological conditions. However, it is still unclear how the sympathetic nerves affect stem cell migration and differentiation in bone regeneration. Distraction osteogenesis is an ideal model of bone regeneration due to its special nature as a self-engineering tissue. In this study, a rat model of mandibular distraction osteogenesis with transection of cervical sympathetic trunk was used to demonstrate that sympathetic denervation can deplete norepinephrine (NE in distraction-induced bone callus, down-regulate β3-adrenergic receptor (adrb3 in bone marrow mesenchymal stem cells (MSCs, and promote MSC migration from perivascular regions to bone-forming units. An in vitro Transwell assay was here used to demonstrate that NE can inhibit stroma-derived factor-1 (SDF-1-induced MSC migration and expression of the migration-related gene matrix metalloproteinase-2 (MMP-2 and downregulate that of the anti-migration gene tissue inhibitor of metalloproteinase-3 (TIMP-3. Knockdown of adrb3 using siRNA abolishes inhibition of MSC migration. An in vitro osteogenic assay was used to show that NE can inhibit the formation of MSC bone nodules and expression of the osteogenic marker genes alkaline phosphatase (ALP, osteocalcin (OCN, and runt-related transcription factor-2 (RUNX2, but knockdown of adrb3 by siRNA can abolish such inhibition of the osteogenic differentiation of MSCs. It is here concluded that sympathetic denervation-induced MSC mobilization in rat mandibular distraction osteogenesis is associated with inhibition of MSC migration and osteogenic differentiation by NE/adrb3 in vitro. These findings may facilitate understanding of the relationship of MSC mobilization and sympathetic nervous system across a wide spectrum of tissue regeneration processes.

  19. Sympathetic denervation-induced MSC mobilization in distraction osteogenesis associates with inhibition of MSC migration and osteogenesis by norepinephrine/adrb3.

    Science.gov (United States)

    Du, Zhaojie; Wang, Lei; Zhao, Yinghua; Cao, Jian; Wang, Tao; Liu, Peng; Zhang, Yabo; Yang, Xinjie; Cheng, Xiaobing; Liu, Baolin; Lei, Delin

    2014-01-01

    The sympathetic nervous system regulates bone formation and resorption under physiological conditions. However, it is still unclear how the sympathetic nerves affect stem cell migration and differentiation in bone regeneration. Distraction osteogenesis is an ideal model of bone regeneration due to its special nature as a self-engineering tissue. In this study, a rat model of mandibular distraction osteogenesis with transection of cervical sympathetic trunk was used to demonstrate that sympathetic denervation can deplete norepinephrine (NE) in distraction-induced bone callus, down-regulate β3-adrenergic receptor (adrb3) in bone marrow mesenchymal stem cells (MSCs), and promote MSC migration from perivascular regions to bone-forming units. An in vitro Transwell assay was here used to demonstrate that NE can inhibit stroma-derived factor-1 (SDF-1)-induced MSC migration and expression of the migration-related gene matrix metalloproteinase-2 (MMP-2) and downregulate that of the anti-migration gene tissue inhibitor of metalloproteinase-3 (TIMP-3). Knockdown of adrb3 using siRNA abolishes inhibition of MSC migration. An in vitro osteogenic assay was used to show that NE can inhibit the formation of MSC bone nodules and expression of the osteogenic marker genes alkaline phosphatase (ALP), osteocalcin (OCN), and runt-related transcription factor-2 (RUNX2), but knockdown of adrb3 by siRNA can abolish such inhibition of the osteogenic differentiation of MSCs. It is here concluded that sympathetic denervation-induced MSC mobilization in rat mandibular distraction osteogenesis is associated with inhibition of MSC migration and osteogenic differentiation by NE/adrb3 in vitro. These findings may facilitate understanding of the relationship of MSC mobilization and sympathetic nervous system across a wide spectrum of tissue regeneration processes. PMID:25144690

  20. Changing the paradigm: the potential for targeted therapy in laryngeal squamous cell carcinoma

    Science.gov (United States)

    Ludwig, Megan L.; Birkeland, Andrew C.; Hoesli, Rebecca; Swiecicki, Paul; Spector, Matthew E.; Brenner, J. Chad

    2016-01-01

    Laryngeal squamous cell carcinoma (LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21st century. PMID:27144065

  1. MSC POOL技术及其发展现状%MSC POOL Technology and Its Development Status

    Institute of Scientific and Technical Information of China (English)

    刘蓉; 李旭

    2011-01-01

    Based on technical research of MSC POOL, the definition and principle of MSC POOL technology are elaborated in a detail. The development status of various manufacturers for MSC POOL technology are summarized. Some typical business examples with MSC POOL technology and the benefits brought by MSC POOL technology in the practical application are analyzed. Finallyt some problems brought by MSC POOL technology and development trend of MSC POOL technology are proposed.%在对MSC POOL技术调研的基础上,详细阐述了MSC POOL技术的定义及原理,然后总结各个厂家针对MSCPOOL技术的发展状况,分析各地的一些典型商用MSC POOL技术实例以及MSC POOL技术在实际应用中所带来的优势,并总结了MSC POOL技术带来的一些问题,展望MSCPOOL技术未来的发展趋势.

  2. [Helper T cell paradigm: Th17 and regulatory T cells involved in autoimmune inflammatory disorders, pathogen defense and allergic diseases].

    Science.gov (United States)

    Noma, Takeshi

    2010-01-01

    The helper T cell paradigm, divided into two distinct subsets, Th1 and Th2 cells, characterized by distinct cytokine and functions, has been expanded to IL-17-producing Th17 cells. Th1 cells producing IFN-γ are involved in delayed-type hypersensitivity, effective in intracellular pathogens defense, while Th2 cells secrete IL-4, IL-5, IL-13 and IL-25 and has a central role in IgE production, eosinophilic inflammation, and the protection for helminthic parasite infection. Th17 cell lineages, expressing IL-17 family of cytokines and IL-23-mediated functions on T cells, plays a role in immune response to fungi and extracellular pathogens and autoimmune inflammatory disorders. Th17 cells are required the combination of IL-6 and TGF-β and the transcription factors, RORC2/RORgt (mice) and STAT3 for differentiation, and produce IL-17, IL-22, IL-17F, IL-21 and CCL20. FOXP3+ regulatory T (Treg) cells produce TGF-β and IL-10, which regulate effector T cells, and thus maintain peripheral tolerance. Four functionally unique CD4+ T cells, including the regulatory T (Treg) cells are now involved in the regulation of immune responses to pathogens, self-antigens and allergens. Any defect in the entire CD4+T cell population might results in human diseases. In this review, the biology of Th17 cells and Treg cells and their role in immune diseases are presented.

  3. Phenotypic, Functional, and Safety Control at Preimplantation Phase of MSC-Based Therapy.

    Science.gov (United States)

    Lech, Wioletta; Figiel-Dabrowska, Anna; Sarnowska, Anna; Drela, Katarzyna; Obtulowicz, Patrycja; Noszczyk, Bartlomiej Henryk; Buzanska, Leonora; Domanska-Janik, Krystyna

    2016-01-01

    Mesenchymal stem cells (MSC) exhibit enormous heterogeneity which can modify their regenerative properties and therefore influence therapeutic effectiveness as well as safety of these cells transplantation. In addition the high phenotypic plasticity of MSC population makes it enormously sensitive to any changes in environmental properties including fluctuation in oxygen concentration. We have shown here that lowering oxygen level far below air atmosphere has a beneficial impact on various parameters characteristic for umbilical cord Wharton Jelly- (WJ-) MSC and adipose tissue- (AD-) derived MSC cultures. This includes their cellular composition, rate of proliferation, and maintenance of stemness properties together with commitment to cell differentiation toward mesodermal and neural lineages. In addition, the culture genomic stability increased significantly during long-term cell passaging and eventually protected cells against spontaneous transformation. Also by comparing of two routinely used methods of MSCs isolation (mechanical versus enzymatic) we have found substantial divergence arising between cell culture properties increasing along the time of cultivation in vitro. Thus, in this paper we highlight the urgent necessity to develop the more sensitive and selective methods for prediction and control cells fate and functioning during the time of growth in vitro. PMID:27651796

  4. MSC POOL网络组网方案研究

    Institute of Scientific and Technical Information of China (English)

    孙志刚; 姜金池

    2015-01-01

    MSC POOL是在3G R5版本中引入软交换核心网的一项重要技术。通过将某一区域的交换机组建成MSC POOL网络,极大地提高了通信网络的安全性。本文通过对MSC POOL技术进行深入研究,提出了一种以MGW媒体网关做NNSF代理的MSC POOL组网方式,并对可行性进行了论证。

  5. Student performance in a newly developed MSc programme

    DEFF Research Database (Denmark)

    Richelsen, Ann Bettina

    2011-01-01

    other than DTUs and allow qualified students to enter the MSc programmes. The focus of the present work is a comparison of how international and Danish students perform within specific modules of the MSc curriculum in Engineering Design and Applied Mechanics at Technical University of Denmark. The...

  6. Dihydrostreptomycin Directly Binds to, Modulates, and Passes through the MscL Channel Pore

    Science.gov (United States)

    Gao, Ya; Li, Hua; Wang, Junmei; Blount, Paul

    2016-01-01

    The primary mechanism of action of the antibiotic dihydrostreptomycin is binding to and modifying the function of the bacterial ribosome, thus leading to decreased and aberrant translation of proteins; however, the routes by which it enters the bacterial cell are largely unknown. The mechanosensitive channel of large conductance, MscL, is found in the vast majority of bacterial species, where it serves as an emergency release valve rescuing the cell from sudden decreases in external osmolarity. While it is known that MscL expression increases the potency of dihydrostreptomycin, it has remained unclear if this effect is due to a direct interaction. Here, we use a combination of genetic screening, MD simulations, and biochemical and mutational approaches to determine if dihydrostreptomycin directly interacts with MscL. Our data strongly suggest that dihydrostreptomycin binds to a specific site on MscL and modifies its conformation, thus allowing the passage of K+ and glutamate out of, and dihydrostreptomycin into, the cell. PMID:27280286

  7. Optimization and translation of MSC-based hyaluronic acid hydrogels for cartilage repair

    Science.gov (United States)

    Erickson, Isaac E.

    2011-12-01

    Traumatic injury and disease disrupt the ability of cartilage to carry joint stresses and, without an innate regenerative response, often lead to degenerative changes towards the premature development of osteoarthritis. Surgical interventions have yet to restore long-term mechanical function. Towards this end, tissue engineering has been explored for the de novo formation of engineered cartilage as a biologic approach to cartilage repair. Research utilizing autologous chondrocytes has been promising, but clinical limitations in their yield have motivated research into the potential of mesenchymal stem cells (MSCs) as an alternative cell source. MSCs are multipotent cells that can differentiate towards a chondrocyte phenotype in a number of biomaterials, but no combination has successfully recapitulated the native mechanical function of healthy articular cartilage. The broad objective of this thesis was to establish an MSC-based tissue engineering approach worthy of clinical translation. Hydrogels are a common class of biomaterial used for cartilage tissue engineering and our initial work demonstrated the potential of a photo-polymerizable hyaluronic acid (HA) hydrogel to promote MSC chondrogenesis and improved construct maturation by optimizing macromer and MSC seeding density. The beneficial effects of dynamic compressive loading, high MSC density, and continuous mixing (orbital shaker) resulted in equilibrium modulus values over 1 MPa, well in range of native tissue. While compressive properties are crucial, clinical translation also demands that constructs stably integrate within a defect. We utilized a push-out testing modality to assess the in vitro integration of HA constructs within artificial cartilage defects. We established the necessity for in vitro pre-maturation of constructs before repair to achieve greater integration strength and compressive properties in situ. Combining high MSC density and gentle mixing resulted in integration strength over 500 k

  8. Mechanical strain downregulates C/EBPβ in MSC and decreases endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Maya Styner

    Full Text Available Exercise prevents marrow mesenchymal stem cell (MSC adipogenesis, reversing trends that accompany aging and osteoporosis. Mechanical input, the in-vitro analogue to exercise, limits PPARγ expression and adipogenesis in MSC. We considered whether C/EBPβ might be mechanoresponsive as it is upstream to PPARγ, and also is known to upregulate endoplasmic reticulum (ER stress. MSC (C3H10T1/2 pluripotent cells as well as mouse marrow-derived MSC were cultured in adipogenic media and a daily mechanical strain regimen was applied. We demonstrate herein that mechanical strain represses C/EBPβ mRNA (0.6-fold ±0.07, p<0.05 and protein (0.4-fold ±0.1, p<0.01 in MSC. SiRNA silencing of β-catenin prevented mechanical repression of C/EBPβ. C/EBPβ overexpression did not override strain's inhibition of adipogenesis, which suggests that mechanical control of C/EBPβ is not the primary site at which adipogenesis is regulated. Mechanical inhibition of C/EBPβ, however, might be critical for further processes that regulate MSC health. Indeed, overexpression of C/EBPβ in MSC induced ER stress evidenced by a dose-dependent increase in the pro-apoptotic CHOP (protein 4-fold ±0.5, p<0.05 and a threshold reduction in the chaperone BiP (protein 0.6-fold ±0.1, p = 0.2; mRNA 0.3-fold ±0.1, p<0.01. ChIP-seq demonstrated a significant association between C/EBPβ and both CHOP and BiP genes. The strain regimen, in addition to decreasing C/EBPβ mRNA (0.5-fold ±0.09, p<0.05, expanded ER capacity as measured by an increase in BiP mRNA (2-fold ±0.2, p<0.05 and protein. Finally, ER stress induced by tunicamycin was ameliorated by mechanical strain as demonstrated by decreased C/EBPβ, increased BiP and decreased CHOP protein expression. Thus, C/EBPβ is a mechanically responsive transcription factor and its repression should counter increases in marrow fat as well as improve skeletal resistance to ER stress.

  9. MSc Thesis: Presentation of Certain New Trends in Noncommutative Geometry

    CERN Document Server

    Buachalla, Réamonn Ó

    2011-01-01

    MSc thesis of the author offering an introduction to the operator algebraic approach to noncommutative geometry, with a treatment of some more advanced elements such as the noncommutative geometry of quantum groups, fuzzy physics, and compact quantum metric spaces.

  10. Binding of fullerenes and nanotubes to MscL

    Science.gov (United States)

    Hilder, Tamsyn A.; Ridone, Pietro; Nakayama, Yoshitaka; Martinac, Boris; Chung, Shin-Ho

    2014-07-01

    Multi-drug resistance is becoming an increasing problem in the treatment of bacterial infections and diseases. The mechanosensitive channel of large conductance (MscL) is highly conserved among prokaryotes. Evidence suggests that a pharmacological agent that can affect the gating of, or block the current through, MscL has significant potential as a new class of antimicrobial compound capable of targeting a range of pathogenic bacteria with minimal side-effects to infected patients. Using molecular dynamics we examine the binding of fullerenes and nanotubes to MscL and demonstrate that both are stable within the MscL pore. We predict that fullerenes will attenuate the flow of ions through MscL by reducing the pore volume available to water and ions, but nanotubes will prevent pore closure resulting in a permanently open pore. Moreover, we confirm experimentally that it is possible to attenuate the flow of ions through MscL using a C60-γ cyclodextrin complex.

  11. NNSF Deployment within MSC Pool Technology%MSC Pool技术中NNSF的部署方式

    Institute of Scientific and Technical Information of China (English)

    龙滔滔

    2008-01-01

    本文首先介绍了MSC Pool的技术原理与组网优势,然后对MSC Pool技术中NNSF的两种部署方式做了重点阐述,说明了由MGW代理实现NNSF的信令组网方式,并且介绍了一种比较可行的组网实现方案.

  12. The large mechanosensitive channel MscL determines bacterial susceptibility to the bacteriocin sublancin 168.

    Science.gov (United States)

    Kouwen, Thijs R H M; Trip, Erik N; Denham, Emma L; Sibbald, Mark J J B; Dubois, Jean-Yves F; van Dijl, Jan Maarten

    2009-11-01

    Bacillus subtilis strain 168 produces the extremely stable and broad-spectrum lantibiotic sublancin 168. Known sublancin 168-susceptible organisms include important pathogens, such as Staphylococcus aureus. Nevertheless, since its discovery, the mode of action of sublancin 168 has remained elusive. The present studies were, therefore, aimed at the identification of cellular determinants for bacterial susceptibility toward sublancin 168. Growth inhibition and competition assays on plates and in liquid cultures revealed that sublancin 168-mediated growth inhibition of susceptible B. subtilis and S. aureus cells is affected by the NaCl concentration in the growth medium. Added NaCl did not influence the production, activity, or stability of sublancin 168 but, instead, lowered the susceptibility of sensitive cells toward this lantibiotic. Importantly, the susceptibility of B. subtilis and S. aureus cells toward sublancin 168 was shown to depend on the presence of the large mechanosensitive channel of conductance MscL. In contrast, MscL was not involved in susceptibility toward the bacteriocin nisin or Pep5. Taken together, our unprecedented results demonstrate that MscL is a critical and specific determinant in bacterial sublancin 168 susceptibility that may serve either as a direct target for this lantibiotic or as a gate of entry to the cytoplasm. PMID:19738010

  13. Nanotechnology convergence and modeling paradigm of sustainable energy system using polymer electrolyte membrane fuel cell as a benchmark example

    International Nuclear Information System (INIS)

    Developments in nanotechnology have led to innovative progress and converging technologies in engineering and science. These demand novel methodologies that enable efficient communications from the nanoscale all the way to decision-making criteria for actual production systems. In this paper, we discuss the convergence of nanotechnology and novel multi-scale modeling paradigms by using the fuel cell system as a benchmark example. This approach includes complex multi-phenomena at different time and length scales along with the introduction of an optimization framework for application-driven nanotechnology research trends. The modeling paradigm introduced here covers the novel holistic integration from atomistic/molecular phenomena to meso/continuum scales. System optimization is also discussed with respect to the reduced order parameters for a coarse-graining procedure in multi-scale model integration as well as system design. The development of a hierarchical multi-scale paradigm consolidates the theoretical analysis and enables large-scale decision-making of process level design, based on first-principles, and therefore promotes the convergence of nanotechnology to sustainable energy technologies.

  14. Nanotechnology convergence and modeling paradigm of sustainable energy system using polymer electrolyte membrane fuel cell as a benchmark example

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Pil Seung; So, Dae Sup; Biegler, Lorenz T.; Jhon, Myung S., E-mail: mj3a@andrew.cmu.edu [Carnegie Mellon University, Department of Chemical Engineering (United States)

    2012-08-15

    Developments in nanotechnology have led to innovative progress and converging technologies in engineering and science. These demand novel methodologies that enable efficient communications from the nanoscale all the way to decision-making criteria for actual production systems. In this paper, we discuss the convergence of nanotechnology and novel multi-scale modeling paradigms by using the fuel cell system as a benchmark example. This approach includes complex multi-phenomena at different time and length scales along with the introduction of an optimization framework for application-driven nanotechnology research trends. The modeling paradigm introduced here covers the novel holistic integration from atomistic/molecular phenomena to meso/continuum scales. System optimization is also discussed with respect to the reduced order parameters for a coarse-graining procedure in multi-scale model integration as well as system design. The development of a hierarchical multi-scale paradigm consolidates the theoretical analysis and enables large-scale decision-making of process level design, based on first-principles, and therefore promotes the convergence of nanotechnology to sustainable energy technologies.

  15. Rationale and design of the first randomized, double-blind, placebo-controlled trial of intramyocardial injection of autologous bone-marrow derived Mesenchymal Stromal Cells in chronic ischemic Heart Failure (MSC-HF Trial)

    DEFF Research Database (Denmark)

    Mathiasen, Anders Bruun; Jørgensen, Erik; Qayyum, Abbas Ali;

    2012-01-01

    Stem cell therapy is an emerging treatment modality in cardiovascular disease. The best cell type and delivery method in different cardiovascular diseases remain to be determined.......Stem cell therapy is an emerging treatment modality in cardiovascular disease. The best cell type and delivery method in different cardiovascular diseases remain to be determined....

  16. Adaptation of MSC/NASTRAN to a supercomputer

    Energy Technology Data Exchange (ETDEWEB)

    Gloudeman, J.F.; Hodge, J.C.

    1982-01-01

    MSC/NASTRAN is a large-scale general purpose digital computer program which solves a wider variety of engineering analysis problems by the finite element method. The program capabilities include static and dynamic structural analysis (linear and nonlinear), heat transfer, acoustics, electromagnetism and other types of field problems. It is used worldwide by large and small companies in such diverse fields as automotive, aerospace, civil engineering, shipbuilding, offshore oil, industrial equipment, chemical engineering, biomedical research, optics and government research. The paper presents the significant aspects of the adaptation of MSC/NASTRAN to the Cray-1. First, the general architecture and predominant functional use of MSC/NASTRAN are discussed to help explain the imperatives and the challenges of this undertaking. The key characteristics of the Cray-1 which influenced the decision to undertake this effort are then reviewed to help identify performance targets. An overview of the MSC/NASTRAN adaptation effort is then given to help define the scope of the project. Finally, some measures of MSC/NASTRAN's operational performance on the Cray-1 are given, along with a few guidelines to help avoid improper interpretation. 17 references.

  17. YidC is required for the assembly of the MscL homopentameric pore

    NARCIS (Netherlands)

    Pop, Ovidiu I.; Soprova, Zora; Koningstein, Gregory; Scheffers, Dirk-Jan; Ulsen, Peter van; Wickström, David; Gier, Jan-Willem de; Luirink, Joen

    2009-01-01

    The mechanosensitive channel with large conductance (MscL) of Escherichia coli is formed by a homopentameric assembly of MscL proteins. Here, we describe MscL biogenesis as determined using in vivo approaches. Evidence is presented that MscL is targeted to the inner membrane via the signal recogniti

  18. An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome

    Science.gov (United States)

    Wu, Yi-Hsuan; Taggart, Janet; Song, Pamela Xiyao; MacDiarmid, Colin; Eide, David J.

    2016-01-01

    The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold) in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5’ end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, β-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5’ UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5’ UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5’ UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome. PMID:27657924

  19. THE EFFECTS OF CULTURE ON KNOWLEDGE MANAGEMENT PRACTICE: A QUALITATIVE CASE STUDY OF MSC STATUS COMPANIES

    Directory of Open Access Journals (Sweden)

    Charmaine Ryan

    2006-01-01

    Full Text Available Knowledge is recognised as being an important asset in organisations these days. Despite this, many organisations are not doing enough to effectively manage this important asset for its competitive advantage. In response to this, knowledge management which is defined as a process that effectively creates, captures, shares and uses organisation-wide knowledge to improve the organisation’s performance was conceived and has since gained widespread acceptance the world over. Despite its widespread acceptance, little is known about the current levels of knowledge management within the Malaysian context, in particular amongst the Multimedia Super Corridor (MSC status companies in Malaysia. Furthermore, the extent to which cultural factors impact upon knowledge management practice in these companies is not known. This study investigated the various cultural factors (collaboration, mutual trust, leadership and incentives/rewards using a multiple case study approach operating within a critical realism research paradigm and found that these factors have impact on the level of knowledge management practice. The study also established that cultural factors do play an important role in facilitating knowledge management practice in these MSC status companies in Malaysia. It was found that collaboration, mutual trust, leadership, kiasu-ism and incentives/rewards have significant impact on the level of knowledge management practice. In view of the findings of this study, it is suggested that the relevant authorities pay adequate attention on these cultural factors to ensure that the knowledge management initiatives undertaken by Malaysian companies are effectively deployed.

  20. MSC POOL工程实施方案研究

    Institute of Scientific and Technical Information of China (English)

    龙滔滔

    2012-01-01

    文章首先介绍MSC POOL技术的原理及优点,然后详细分析了在新建或改造MSC POOL过程中需要注意的问题,包括:池区规划的原则、需要规划的数据、四种POOL内组网方案的比较以及信令组网方式的选择,并总结了NRI与TMSI及系统容量的关系,为整个MSC POOL网络的工程实施提供了经验依据.

  1. Osteogenic Differentiation of MSC through Calcium Signaling Activation: Transcriptomics and Functional Analysis.

    Directory of Open Access Journals (Sweden)

    Federica Viti

    Full Text Available The culture of progenitor mesenchymal stem cells (MSC onto osteoconductive materials to induce a proper osteogenic differentiation and mineralized matrix regeneration represents a promising and widely diffused experimental approach for tissue-engineering (TE applications in orthopaedics. Among modern biomaterials, calcium phosphates represent the best bone substitutes, due to their chemical features emulating the mineral phase of bone tissue. Although many studies on stem cells differentiation mechanisms have been performed involving calcium-based scaffolds, results often focus on highlighting production of in vitro bone matrix markers and in vivo tissue ingrowth, while information related to the biomolecular mechanisms involved in the early cellular calcium-mediated differentiation is not well elucidated yet. Genetic programs for osteogenesis have been just partially deciphered, and the description of the different molecules and pathways operative in these differentiations is far from complete, as well as the activity of calcium in this process. The present work aims to shed light on the involvement of extracellular calcium in MSC differentiation: a better understanding of the early stage osteogenic differentiation program of MSC seeded on calcium-based biomaterials is required in order to develop optimal strategies to promote osteogenesis through the use of new generation osteoconductive scaffolds. A wide spectrum of analysis has been performed on time-dependent series: gene expression profiles are obtained from samples (MSC seeded on calcium-based scaffolds, together with related microRNAs expression and in vivo functional validation. On this basis, and relying on literature knowledge, hypotheses are made on the biomolecular players activated by the biomaterial calcium-phosphate component. Interestingly, a key role of miR-138 was highlighted, whose inhibition markedly increases osteogenic differentiation in vitro and enhance ectopic bone

  2. Osteogenic Differentiation of MSC through Calcium Signaling Activation: Transcriptomics and Functional Analysis.

    Science.gov (United States)

    Viti, Federica; Landini, Martina; Mezzelani, Alessandra; Petecchia, Loredana; Milanesi, Luciano; Scaglione, Silvia

    2016-01-01

    The culture of progenitor mesenchymal stem cells (MSC) onto osteoconductive materials to induce a proper osteogenic differentiation and mineralized matrix regeneration represents a promising and widely diffused experimental approach for tissue-engineering (TE) applications in orthopaedics. Among modern biomaterials, calcium phosphates represent the best bone substitutes, due to their chemical features emulating the mineral phase of bone tissue. Although many studies on stem cells differentiation mechanisms have been performed involving calcium-based scaffolds, results often focus on highlighting production of in vitro bone matrix markers and in vivo tissue ingrowth, while information related to the biomolecular mechanisms involved in the early cellular calcium-mediated differentiation is not well elucidated yet. Genetic programs for osteogenesis have been just partially deciphered, and the description of the different molecules and pathways operative in these differentiations is far from complete, as well as the activity of calcium in this process. The present work aims to shed light on the involvement of extracellular calcium in MSC differentiation: a better understanding of the early stage osteogenic differentiation program of MSC seeded on calcium-based biomaterials is required in order to develop optimal strategies to promote osteogenesis through the use of new generation osteoconductive scaffolds. A wide spectrum of analysis has been performed on time-dependent series: gene expression profiles are obtained from samples (MSC seeded on calcium-based scaffolds), together with related microRNAs expression and in vivo functional validation. On this basis, and relying on literature knowledge, hypotheses are made on the biomolecular players activated by the biomaterial calcium-phosphate component. Interestingly, a key role of miR-138 was highlighted, whose inhibition markedly increases osteogenic differentiation in vitro and enhance ectopic bone formation in vivo

  3. MSC.Patran中的单位制转换%Units' Transition in Software of MSC.Patran

    Institute of Scientific and Technical Information of China (English)

    袁晓金; 段志梅

    2011-01-01

    以CAE为基础的虚拟产品开发(VPD)是实现创新设计的最主要技术保障.目前,在国际上被公认的最优秀的、应用最广泛的前后处理软件首推MSC公司的Patran软件.MSC.Patran是一个集成的并行框架式有限元前后处理及分析仿真系统.进行有限元分析计算必然涉及到单位制的转换问题,否则会因单位制产生错误.介绍了运用MSC.Patran软件时,正确进行单位制的转换的方法.%VPD on the basis of CAE is the best important technology guarantee of actual innovation designs. Now, MSC. Patran is recognized as the optimal and broad software of fore-and-aft disposal in the intemational. MSC. Patran is the compositive and side-by-side frame type system,which is used in the fore-and-aft disposal, analysis and simulation. There for units' transition is necessary in the FEA,otherwise,the system goes wrong. This paper introduces the means of unit system transition,handling MSC Patran software.

  4. Reversibility of cellular aging by reprogramming through an embryonic-like state : a new paradigm for human cell rejuvenation

    Directory of Open Access Journals (Sweden)

    Jean-Marc Lemaitre

    2014-01-01

    Full Text Available Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs provides a unique opportunity to derive patient-specific stem cells with potential application in autologous tissue replacement therapies and without the ethical concerns of Embryonic Stem Cells (hESC. However, this strategy still suffers from several hurdles that need to be overcome before clinical applications. Among them, cellular senescence, which contributes to aging and restricted longevity, has been described as a barrier to the derivation of iPSCs. This suggests that aging might be an important limitation for therapeutic purposes for elderly individuals. Senescence is characterized by an irreversible cell cycle arrest in response to various forms of stress, including activation of oncogenes, shortened telomeres, DNA damage, oxidative stress, and mitochondrial dysfunction. To overcome this barrier, we developed an optimized 6-factor-based reprogramming protocol that is able to cause efficient reversing of cellular senescence and reprogramming into iPSCs. We demonstrated that iPSCs derived from senescent and centenarian fibroblasts have reset telomere size, gene expression profiles, oxidative stress, and mitochondrial metabolism, and are indistinguishable from hESC. Finally, we demonstrate that re-differentiation led to rejuvenated cells with a reset cellular physiology, defining a new paradigm for human cell rejuvenation. We discuss the molecular mechanisms involved in cell reprogramming of senescent cells

  5. MSC Pool组网规划研究及问题分析

    Institute of Scientific and Technical Information of China (English)

    黄嘉

    2007-01-01

    简要介绍了MSC Pool的技术原理,对目前MSC Pool技术应用存在的问题进行了分析,并针对引入MSC Pool带来的影响进行了探讨,重点讨论了 MSC Pool组网的要点和原则.并给出了MSC Pool组网规划的相关建议.

  6. Mutations in a Conserved Domain of E. coli MscS to the Most Conserved Superfamily Residue Leads to Kinetic Changes.

    Directory of Open Access Journals (Sweden)

    Hannah R Malcolm

    Full Text Available In Escherichia coli (E. coli the mechanosensitive channel of small conductance, MscS, gates in response to membrane tension created from acute external hypoosmotic shock, thus rescuing the bacterium from cell lysis. E. coli MscS is the most well studied member of the MscS superfamily of channels, whose members are found throughout the bacterial and plant kingdoms. Homology to the pore lining helix and upper vestibule domain of E. coli MscS is required for inclusion into the superfamily. Although highly conserved, in the second half of the pore lining helix (TM3B, E. coli MscS has five residues significantly different from other members of the superfamily. In superfamilies such as this, it remains unclear why variations within such a homologous region occur: is it tolerance of alternate residues, or does it define functional variance within the superfamily? Point mutations (S114I/T, L118F, A120S, L123F, F127E/K/T and patch clamp electrophysiology were used to study the effect of changing these residues in E. coli MscS on sensitivity and gating. The data indicate that variation at these locations do not consistently lead to wildtype channel phenotypes, nor do they define large changes in mechanosensation, but often appear to effect changes in the E. coli MscS channel gating kinetics.

  7. Paradigm Shift

    OpenAIRE

    Besancenot, Damien; Dogguy, Habib

    2011-01-01

    This paper analyses the consequences of young researchers' scientifc choice on the dynamics of sciences. We develop a simple two state mean field game model to analyze the competition between two paradigms based on Kuhn's theory of scientifc revolutions. At the beginning of their career, young researchers choose the paradigm in which they want to work according to social and personal motivations. Despite the possibility of multiple equilibria the model exhibits at least one stable solution in...

  8. Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering.

    Science.gov (United States)

    Steinmetz, Neven J; Aisenbrey, Elizabeth A; Westbrook, Kristofer K; Qi, H Jerry; Bryant, Stephanie J

    2015-07-01

    A bioinspired multi-layer hydrogel was developed for the encapsulation of human mesenchymal stem cells (hMSCs) as a platform for osteochondral tissue engineering. The spatial presentation of biochemical cues, via incorporation of extracellular matrix analogs, and mechanical cues, via both hydrogel crosslink density and externally applied mechanical loads, were characterized in each layer. A simple sequential photopolymerization method was employed to form stable poly(ethylene glycol)-based hydrogels with a soft cartilage-like layer of chondroitin sulfate and low RGD concentrations, a stiff bone-like layer with high RGD concentrations, and an intermediate interfacial layer. Under a compressive load, the variation in hydrogel stiffness within each layer produced high strains in the soft cartilage-like layer, low strains in the stiff bone-like layer, and moderate strains in the interfacial layer. When hMSC-laden hydrogels were cultured statically in osteochondral differentiation media, the local biochemical and matrix stiffness cues were not sufficient to spatially guide hMSC differentiation after 21 days. However dynamic mechanical stimulation led to differentially high expression of collagens with collagen II in the cartilage-like layer, collagen X in the interfacial layer and collagen I in the bone-like layer and mineral deposits localized to the bone layer. Overall, these findings point to external mechanical stimulation as a potent regulator of hMSC differentiation toward osteochondral cellular phenotypes.

  9. M.Sc. in Civil and Structural Engineering

    DEFF Research Database (Denmark)

    The following pages contain a list of project ideas proposed by the scientific staff at the Department of Civil Engineering, Aalborg University, and a number of companies. Most of the project ideas in this catalogue may form the basis for long and short master projects as well as regular 3rd...... semester projects at the M.Sc. programme in Civil and Structural Engineering....

  10. Fit for purpose? Evaluation of an MSc. in Medical Physics.

    LENUS (Irish Health Repository)

    van der Putten, W J

    2014-05-01

    The National University of Ireland in Galway established a Master in Science (MSc.) program in medical physics in 2002. The course was designed to be 90 ECTS(1) credits and of one calendar year duration. From the outset the MSc. was designed to be part of an overall medical physics training program. MSc. programs are now widely used as part of the training and education of medical physicists. There is however paucity of data on the effectiveness of such courses and the purpose of the study reported here is to provide information on one particular MSc. course in medical physics. This is relevant to medical physicists who are involved in the development and running of medical physics training programs. The study used as methodology the Kirkpatrick levels of professional training. It was conducted through an online survey, both from students who graduated from the course and from students who were in the process of completing the course. The survey proved to be an effective way to determine attributes of modules such as learning outcomes, knowledge imparted, quality of teaching materials and others. The survey proved to be remarkably able to demonstrate interventions in the individual course modules. Although the course was shown to be effective in the imparting of the knowledge required to become a qualified medical physicist several areas for improvement were identified. These are mainly in the areas of increased practical experience and in course delivery.

  11. M.Sc. in Civil and Structural Engineering

    DEFF Research Database (Denmark)

    This catalogue contains a list of project ideas proposed by the scientific staff at the Department of Civil Engineering, Aalborg University, and a number of companies. Most of the project ideas in this catalogue may form the basis for long and short candidate projects as well as regular 3rd...... semester projects at the M.Sc. programme in Civil and Structural Engineering....

  12. M.Sc. in Civil and Structural Engineering

    DEFF Research Database (Denmark)

    The catalogue contain a list of project ideas proposed by the scientific staff at the Department of Civil Engineering, Aalborg University, and a number of companies. Most of the project ideas in this catalogue may form the basis for long and short candidate projects as well as regular 3rd semester...... projects at the M.Sc. programme in Civil and Structural Engineering....

  13. M.Sc. in Civil and Structural Engineering

    DEFF Research Database (Denmark)

    Clausen, Johan

    The report contain a list of project ideas proposed by the scientific staff at the Department of Civil Engineering, Aalborg University, and a number of companies. Most of the project ideas in this catalogue may form the basis for long and short candidate projects as well as regular 3rd semester...... projects at the M.Sc. programme in Civil and Structural Engineering....

  14. MSc degree in color technology for the automotive sector

    Science.gov (United States)

    Martinez-Verdu, F.; Perales, E.; Chorro, E.; Viqueira, V.; Gilabert, E.

    2014-07-01

    Nowadays, the measurement and management of color quality of the gonio-apparent materials is complex, but highly demanded in many industrial sectors, as automotive, cosmetics, plastics for consumer electronics, printing inks, architectural coatings, etc. It is necessary to control complex instrumentation and to do visual assessments of texture and color differences to get, for instance, a visual harmony in car bodies; and a profound knowledge of physics and chemistry of special-effect pigments for their optical formulation to obtain attractive visual effects in coatings, plastics, etc, combining among them and with solid pigments. From University of Alicante, for the academic year 2013-14, we are organizing the first MSc degree in Color Technology for the Automotive Sector, with a design of contents embracing CIE colorimetry and visual perception, included the AUDI2000 color difference formula, instrumentation and color management software, fundamentals of coatings and plastics in the automotive sector, and, optical formulation of pigments. The MSc syllabus, with 60 ECTS, is designed to be taught in two semesters: from September to February with on classroom theoretical and practical activities, and, from March to June at virtual level, with internships of training in some companies. Therefore, the MSc Thesis would be the performance report during the internship in companies or research institutions. Some multinational companies, both as car makers and coatings and plastics providers, from European and non-European countries have already shown their support and interest in welcoming students for specific training, even some job offers when the first MSc edition finishes.

  15. The Application of MSC POOL Technology in Mobile Communication%MSC POOL技术在移动通信中的应用

    Institute of Scientific and Technical Information of China (English)

    昂松鹤

    2014-01-01

    该文通过对MSC Pool技术介绍与优势的分析,阐明MSC Pool在软交换组网中的应用的重要性,分析了MSC POOL技术的关键点以及未来发展趋势,说明了MSC pool的实现方式、优缺点等问题。并对未来网络的展望。%This paper clarifies the importance of the use of MSC Pool in softswitch network through the introduction of MSC Pool and the analysis of its advantage. The paper also analyses the key points of MSC POOL and predicts its trend, which de-scribes its realization methods as well as its benefits and limits. At the end of this paper it looks ahead to the future of network.

  16. The first systematic analysis of 3D rapid prototyped poly(ε-caprolactone) scaffolds manufactured through BioCell printing: the effect of pore size and geometry on compressive mechanical behaviour and in vitro hMSC viability

    International Nuclear Information System (INIS)

    Novel additive manufacturing processes are increasingly recognized as ideal techniques to produce 3D biodegradable structures with optimal pore size and spatial distribution, providing an adequate mechanical support for tissue regeneration while shaping in-growing tissues. With regard to the mechanical and biological performances of 3D scaffolds, pore size and geometry play a crucial role. In this study, a novel integrated automated system for the production and in vitro culture of 3D constructs, known as BioCell Printing, was used only to manufacture poly(ε-caprolactone) scaffolds for tissue engineering; the influence of pore size and shape on their mechanical and biological performances was investigated. Imposing a single lay-down pattern of 0°/90° and varying the filament distance, it was possible to produce scaffolds with square interconnected pores with channel sizes falling in the range of 245–433 µm, porosity 49–57% and a constant road width. Three different lay-down patterns were also adopted (0°/90°, 0°/60/120° and 0°/45°/90°/135°), thus resulting in scaffolds with quadrangular, triangular and complex internal geometries, respectively. Mechanical compression tests revealed a decrease of scaffold stiffness with the increasing porosity and number of deposition angles (from 0°/90° to 0°/45°/90°/135°). Results from biological analysis, carried out using human mesenchymal stem cells, suggest a strong influence of pore size and geometry on cell viability. On the other hand, after 21 days of in vitro static culture, it was not possible to detect any significant variation in terms of cell morphology promoted by scaffold topology. As a first systematic analysis, the obtained results clearly demonstrate the potential of the BioCell Printing process to produce 3D scaffolds with reproducible well organized architectures and tailored mechanical properties. (paper)

  17. Safety paradigm: genetic evaluation of therapeutic grade human embryonic stem cells

    OpenAIRE

    Stephenson, Emma; Ogilvie, Caroline Mackie; Patel, Heema; Cornwell, Glenda; Jacquet, Laureen; Kadeva, Neli; Braude, Peter; Ilic, Dusko

    2010-01-01

    The use of stem cells for regenerative medicine has captured the imagination of the public, with media attention contributing to rising expectations of clinical benefits. Human embryonic stem cells (hESCs) are the best model for capital investment in stem cell therapy and there is a clear need for their robust genetic characterization before scaling-up cell expansion for that purpose. We have to be certain that the genome of the starting material is stable and normal, but the limited resoluti...

  18. MSc Agriculture students working with ex-campus stakeholders

    DEFF Research Database (Denmark)

    Langer, Vibeke; Lund, Mogens; Bendevis, Mira Arpe

    2014-01-01

    both on BSc and MSc level. For many students this results in concerns whether their knowledge, skills and competencies are sufficient when confronted with reality in a job, i.e. in a lack of professional confidence. Therefore when revising the program we focused on competences in contextualizing......In the MSc program in Agriculture at University of Copenhagen we experience that both domestic and international students increasingly enter the programme without a contextual background of “agriculture” and with solid, but fragmented disciplinary and applied knowledge acquired in other courses...... in collaboration with stakeholders. Students are physically on the partner enterprise four times, altogether three weeks, and use Kolb’s learning cycle as a guiding reference through a structured work process. Deliverables from the course are a scientific group report, a group partner document, a group learning...

  19. Shifting paradigms? Reflections on regenerative medicine, embryonic stem cells and pharmaceuticals

    OpenAIRE

    Wainwright, SP; Michael, M.; Williams, C

    2008-01-01

    Will human embryonic stem (hES) cells lead to a revolutionary new regenerative medicine? We begin to answer this question by drawing on interviews with scientists and clinicians from leading labs and clinics in the UK and the USA, exploring their views on the bench-bedside interface in the fields of hES cells, neuroscience and diabetes. We employ Bourdieu's concepts of field, habitus and capital in order to understand stem cell science and cell transplantation. We also build on research on th...

  20. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm.

    Science.gov (United States)

    Hirahara, Kiyoshi; Nakayama, Toshinori

    2016-04-01

    CD4(+)T cells are crucial for directing appropriate immune responses during host defense and for the pathogenesis of inflammatory diseases. In addition to the classical biphasic model of differentiation of T-helper 1 (Th1) and Th2 cells, unexpected increases in the numbers of CD4(+)T-cell subsets, including Th17, Th9, T follicular-helper (Tfh) and T-regulatory (Treg) cells, have been recognized. In the present review, we focus on how these various T-helper cell subsets contribute to the pathogenesis of immune-mediated inflammatory diseases. In particular, we focus on multiple sclerosis, psoriasis and asthma as typical model diseases in which multiple T-helper cell subsets have recently been suggested to play a role. We will also discuss various unique sub-populations of T-helper cells that have been identified. First, we will introduce the heterogeneous T-helper cell subsets, which are classified by their simultaneous expression of multiple key transcription factors. We will also introduce different kinds of memory-type Th2 cells, which are involved in the pathogenesis of chronic type-2 immune-related diseases. Finally, we will discuss the molecular mechanisms underlying the generation of the plasticity and heterogeneity of T-helper cell subsets. The latest progress in the study of T-helper cell subsets has forced us to reconsider the etiology of immune-mediated inflammatory diseases beyond the model based on the Th1/Th2 balance. To this end, we propose another model--the pathogenic T-helper population disease-induction model--as a possible mechanism for the induction and/or persistence of immune-mediated inflammatory diseases. PMID:26874355

  1. Using PAFEC as a preprocessor for MSC/NASTRAN

    Energy Technology Data Exchange (ETDEWEB)

    Gray, W.H.; Baudry, T.V.

    1983-01-01

    Programs for Automatic Finite Element Calculations (PAFEC) is a general-purpose, three-dimensional, linear and nonlinear finite element program. PAFEC's features include free-format input using engineering keywords, powerful mesh-generating facilities, sophisticated database management procedures, and extensive data validation checks. Presented here is a description of a software interface that permits PAFEC to be used as a preprocessor for MSC/NASTRAN. This user-friendly software, called PAFMSC, frees the stress analyst from the laborious and error-prone procedure of creating and debugging a rigid-format MSC/NASTRAN bulk data deck. By interactively creating and debugging a finite element model with PAFEC, thus taking full advantage of the free-format, engineering-keyword-oriented data structure of PAFEC, the stress analyst can drastically reduce the amount of time spent during model generation. The PAFMSC software will automatically convert a PAFEC data structure into an MSC/NASTRAN bulk data deck. The capabilities and limitations of the PAFMSC software are fully discussed in the following report.

  2. Lactococcus lactis Uses MscL as Its Principal Mechanosensitive Channel

    NARCIS (Netherlands)

    Folgering, Joost H.A.; Moe, Paul C.; Schuurman-Wolters, Gea K.; Blount, Paul; Poolman, Bert

    2005-01-01

    The functions of the mechanosensitive channels from Lactococcus lactis were determined by biochemical, physiological, and electrophysiological methods. Patchclamp studies showed that the genes yncB and mscL encode MscS and MscL-like channels, respectively, when expressed in Escherichia coli or if th

  3. Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy

    OpenAIRE

    Hipp, Jason; Atala, Anthony

    2004-01-01

    Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs which is worsening yearly due to the aging population. Scientists in the field of tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Both therapeutic cloning (nucleus from a donor cell...

  4. The T helper type 17/regulatory T cell paradigm in pregnancy.

    Science.gov (United States)

    Figueiredo, Ana Sofia; Schumacher, Anne

    2016-05-01

    T helper type 17 (Th17) and regulatory T (Treg) cells are active players in the establishment of tolerance and defence. These attributes of the immune system enmesh to guarantee the right level of protection. The healthy immune system, on the one hand, recognizes and eliminates dangerous non-self pathogens and, on the other hand, protects the healthy self. However, there are circumstances where this fine balance is disrupted. In fact, in situations such as in pregnancy, the foreign fetal antigens challenge the maternal immune system and Treg cells will dominate Th17 cells to guarantee fetal survival. In other situations such as autoimmunity, where the Th17 responses are often overwhelming, the immune system shifts towards an inflammatory profile and attacks the healthy tissue from the self. Interestingly, autoimmune patients have meliorating symptoms during pregnancy. This connects with the antagonist role of Th17 and Treg cells, and their specific profiles during these two immune challenging situations. In this review, we put into perspective the Th17/Treg ratio during pregnancy and autoimmunity, as well as in pregnant women with autoimmune conditions. We further review existing systems biology approaches that study specific mechanisms of these immune cells using mathematical modelling and we point out possible future directions of investigation. Understanding what maintains or disrupts the balance between these two opponent yet reciprocal cells in healthy physiological settings, sheds light into the development of innovative pharmacological approaches to fight pregnancy loss and autoimmunity.

  5. New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo.

    Science.gov (United States)

    Palombo, Marco; Ligneul, Clémence; Najac, Chloé; Le Douce, Juliette; Flament, Julien; Escartin, Carole; Hantraye, Philippe; Brouillet, Emmanuel; Bonvento, Gilles; Valette, Julien

    2016-06-14

    The brain is one of the most complex organs, and tools are lacking to assess its cellular morphology in vivo. Here we combine original diffusion-weighted magnetic resonance (MR) spectroscopy acquisition and novel modeling strategies to explore the possibility of quantifying brain cell morphology noninvasively. First, the diffusion of cell-specific metabolites is measured at ultra-long diffusion times in the rodent and primate brain in vivo to observe how cell long-range morphology constrains metabolite diffusion. Massive simulations of particles diffusing in synthetic cells parameterized by morphometric statistics are then iterated to fit experimental data. This method yields synthetic cells (tentatively neurons and astrocytes) that exhibit striking qualitative and quantitative similarities with histology (e.g., using Sholl analysis). With our approach, we measure major interspecies difference regarding astrocytes, whereas dendritic organization appears better conserved throughout species. This work suggests that the time dependence of metabolite diffusion coefficient allows distinguishing and quantitatively characterizing brain cell morphologies noninvasively. PMID:27226303

  6. Safety paradigm: genetic evaluation of therapeutic grade human embryonic stem cells.

    Science.gov (United States)

    Stephenson, Emma; Ogilvie, Caroline Mackie; Patel, Heema; Cornwell, Glenda; Jacquet, Laureen; Kadeva, Neli; Braude, Peter; Ilic, Dusko

    2010-12-01

    The use of stem cells for regenerative medicine has captured the imagination of the public, with media attention contributing to rising expectations of clinical benefits. Human embryonic stem cells (hESCs) are the best model for capital investment in stem cell therapy and there is a clear need for their robust genetic characterization before scaling-up cell expansion for that purpose. We have to be certain that the genome of the starting material is stable and normal, but the limited resolution of conventional karyotyping is unable to give us such assurance. Advanced molecular cytogenetic technologies such as array comparative genomic hybridization for identifying chromosomal imbalances, and single nucleotide polymorphism analysis for identifying ethnic background and loss of heterozygosity should be introduced as obligatory diagnostic tests for each newly derived hESC line before it is deposited in national stem cell banks. If this new quality standard becomes a requirement, as we are proposing here, it would facilitate and accelerate the banking process, since end-users would be able to select the most appropriate line for their particular application, thus improving efficiency and streamlining the route to manufacturing therapeutics. The pharmaceutical industry, which may use hESC-derived cells for drug screening, should not ignore their genomic profile as this may risk misinterpretation of results and significant waste of resources. PMID:20826474

  7. New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo

    Science.gov (United States)

    Palombo, Marco; Ligneul, Clémence; Najac, Chloé; Le Douce, Juliette; Flament, Julien; Escartin, Carole; Hantraye, Philippe; Brouillet, Emmanuel; Bonvento, Gilles; Valette, Julien

    2016-01-01

    The brain is one of the most complex organs, and tools are lacking to assess its cellular morphology in vivo. Here we combine original diffusion-weighted magnetic resonance (MR) spectroscopy acquisition and novel modeling strategies to explore the possibility of quantifying brain cell morphology noninvasively. First, the diffusion of cell-specific metabolites is measured at ultra-long diffusion times in the rodent and primate brain in vivo to observe how cell long-range morphology constrains metabolite diffusion. Massive simulations of particles diffusing in synthetic cells parameterized by morphometric statistics are then iterated to fit experimental data. This method yields synthetic cells (tentatively neurons and astrocytes) that exhibit striking qualitative and quantitative similarities with histology (e.g., using Sholl analysis). With our approach, we measure major interspecies difference regarding astrocytes, whereas dendritic organization appears better conserved throughout species. This work suggests that the time dependence of metabolite diffusion coefficient allows distinguishing and quantitatively characterizing brain cell morphologies noninvasively. PMID:27226303

  8. Fluctuating paradigm

    OpenAIRE

    Simmons, L. W.; Tomkins, J. L.; Kotiaho, J. S.; Hunt, J.

    1999-01-01

    A prominent paradigm in evolutionary biology over the last ten years has been the role of fluctuating asymmetry in sexual selection. Fluctuating asymmetry in bilaterally paired traits, and in particular sexual traits, has been proposed to be a reliable indicator of individual quality and the focus of selection through sexual competition and attractiveness. We surveyed the literature on fluctuating asymmetry and sexual selection and found a marked chronological decline in the proportion of stu...

  9. Influence of electrospun fiber mesh size on hMSC oxygen metabolism in 3D collagen matrices: experimental and theoretical evidences.

    Science.gov (United States)

    Guaccio, Angela; Guarino, Vincenzo; Perez, Marco A Alvarez-; Cirillo, Valentina; Netti, Paolo A; Ambrosio, Luigi

    2011-08-01

    The traditional paradigm of tissue engineering of regenerating in vitro tissue or organs, through the combination of an artificial matrix and a cellular population has progressively changed direction. The most recent concept is the realization of a fully functional biohybrid, where both, the artificial and the biotic phase, concur in the formation of the novel organic matter. In this direction, interest is growing in approaches taking advantage of the control at micro- and nano-scale of cell material interaction based on the realization of elementary tassels of cells and materials which constitute the beginning point for the expansion of 3D more complex structures. Since a spontaneous assembly of all these components is expected, however, it becomes more fundamental than ever to define the features influencing cellular behavior, either they were material functional properties, or material architecture. In this work, it has been investigated the direct effect of electrospun fiber sizes on oxygen metabolism of h-MSC cells, when any other culture parameter was kept constant. To this aim, thin PCL electrospun membranes, with micro- and nano-scale texturing, were layered between two collagen slices up to create a sandwich structure (µC-PCL-C and nC-PCL-C). Cells were seeded on membranes, and the oxygen consumption was determined by a phosphorescence quenching technique. Results indicate a strong effect of the architecture of scaffolds on cell metabolism, also revealed by the increasing of HIF1-α gene expression in nC-PCL-C. These findings offer new insights into the role of materials in specific cell activities, also implying the existence of very interesting criteria for the control of tissue growth through the tuning of scaffold architecture.

  10. Application of MSC POOL Technology in the Mobile Softswitch Network%MSC POOL技术在移动软交换组网中的应用

    Institute of Scientific and Technical Information of China (English)

    韩东红

    2014-01-01

    The application of MSC Pool in mobile softswitch network is very important. Its technology is the future development trend of softswitch. This article illustrates the application of MSC POOL and its advantages and disadvantages.%MSC POOL在移动软交换组网应用中非常重要,它的技术是未来软交换发展的趋势。本文说明MSC POOL的应用及优缺点等。

  11. Change of paradigm: CD8+ T cells as important helper for CD4+ T cells during asthma and autoimmune encephalomyelitis

    OpenAIRE

    Huber, Magdalena; Lohoff, Michael

    2015-01-01

    Summary The activation of naive CD4+ and CD8+ T cells in response to antigen and their subsequent proliferation and differentiation into effectors are important features of a cell-mediated immune response. CD4+ T cells (also known as T helper cells, Th) differentiate into several subpopulations including Th1, Th2, Th9, Th17, Tfh and Treg cells, characterized by specific cytokine profiles and effector functions. However, recent evidence indicates that CD8+ T cells (termed cytotoxic T lymphocyt...

  12. Transport across the cell-membrane dictates nanoparticle fate and toxicity: a new paradigm in nanotoxicology

    Science.gov (United States)

    Guarnieri, Daniela; Sabella, Stefania; Muscetti, Ornella; Belli, Valentina; Malvindi, Maria Ada; Fusco, Sabato; de Luca, Elisa; Pompa, Pier Paolo; Netti, Paolo A.

    2014-08-01

    The toxicity of metallic nanoparticles (MNPs) has been fully ascertained, but the mechanisms underlying their cytotoxicity remain still largely unclear. Here we demonstrate that the cytotoxicity of MNPs is strictly reliant on the pathway of cellular internalization. In particular, if otherwise toxic gold, silver, and iron oxide NPs are forced through the cell membrane bypassing any form of active mechanism (e.g., endocytosis), no significant cytotoxic effect is registered. Pneumatically driven NPs across the cell membrane show a different distribution within the cytosol compared to NPs entering the cell by active endocytosis. Specifically, they exhibit free random Brownian motions within the cytosol and do not accumulate in lysosomes. Results suggest that intracellular accumulation of metallic nanoparticles into endo-lysosomal compartments is the leading cause of nanotoxicity, due to consequent nanoparticle degradation and in situ release of metal ions.The toxicity of metallic nanoparticles (MNPs) has been fully ascertained, but the mechanisms underlying their cytotoxicity remain still largely unclear. Here we demonstrate that the cytotoxicity of MNPs is strictly reliant on the pathway of cellular internalization. In particular, if otherwise toxic gold, silver, and iron oxide NPs are forced through the cell membrane bypassing any form of active mechanism (e.g., endocytosis), no significant cytotoxic effect is registered. Pneumatically driven NPs across the cell membrane show a different distribution within the cytosol compared to NPs entering the cell by active endocytosis. Specifically, they exhibit free random Brownian motions within the cytosol and do not accumulate in lysosomes. Results suggest that intracellular accumulation of metallic nanoparticles into endo-lysosomal compartments is the leading cause of nanotoxicity, due to consequent nanoparticle degradation and in situ release of metal ions. Electronic supplementary information (ESI) available. See DOI

  13. Paternal age and telomere length in twins: the germ stem cell selection paradigm.

    Science.gov (United States)

    Hjelmborg, Jacob B; Dalgård, Christine; Mangino, Massimo; Spector, Tim D; Halekoh, Ulrich; Möller, Sören; Kimura, Masayuki; Horvath, Kent; Kark, Jeremy D; Christensen, Kaare; Kyvik, Kirsten O; Aviv, Abraham

    2015-08-01

    Telomere length, a highly heritable trait, is longer in offspring of older fathers. This perplexing feature has been attributed to the longer telomeres in sperm of older men and it might be an 'epigenetic' mechanism through which paternal age plays a role in telomere length regulation in humans. Based on two independent (discovery and replication) twin studies, comprising 889 twin pairs, we show an increase in the resemblance of leukocyte telomere length between dizygotic twins of older fathers, which is not seen in monozygotic twins. This phenomenon might result from a paternal age-dependent germ stem cell selection process, whereby the selected stem cells have longer telomeres, are more homogenous with respect to telomere length, and share resistance to aging.

  14. "String theory" of c-kit(pos) cardiac cells: a new paradigm regarding the nature of these cells that may reconcile apparently discrepant results.

    Science.gov (United States)

    Keith, Matthew C L; Bolli, Roberto

    2015-03-27

    Although numerous preclinical investigations have consistently demonstrated salubrious effects of c-kit(pos) cardiac cells administered after myocardial infarction, the mechanism of action remains highly controversial. We and others have found little or no evidence that these cells differentiate into mature functional cardiomyocytes, suggesting paracrine effects. In this review, we propose a new paradigm predicated on a comprehensive analysis of the literature, including studies of cardiac development; we have (facetiously) dubbed this conceptual construct "string theory" of c-kit(pos) cardiac cells because it reconciles multifarious and sometimes apparently discrepant results. There is strong evidence that, during development, the c-kit receptor is expressed in different pools of cardiac progenitors (some capable of robust cardiomyogenesis and others with little or no contribution to myocytes). Accordingly, c-kit positivity, in itself, does not define the embryonic origins, lineage capabilities, or differentiation capacities of specific cardiac progenitors. C-kit(pos) cells derived from the first heart field exhibit cardiomyogenic potential during development, but these cells are likely depleted shortly before or after birth. The residual c-kit(pos) cells found in the adult heart are probably of proepicardial origin, possess a mesenchymal phenotype (resembling bone marrow mesenchymal stem/stromal cells), and are capable of contributing significantly only to nonmyocytic lineages (fibroblasts, smooth muscle cells, and endothelial cells). If these 2 populations (first heart field and proepicardium) express different levels of c-kit, the cardiomyogenic potential of first heart field progenitors might be reconciled with recent results of c-kit(pos) cell lineage tracing studies. The concept that c-kit expression in the adult heart identifies epicardium-derived, noncardiomyogenic precursors with a mesenchymal phenotype helps to explain the beneficial effects of c

  15. "String theory" of c-kit(pos) cardiac cells: a new paradigm regarding the nature of these cells that may reconcile apparently discrepant results.

    Science.gov (United States)

    Keith, Matthew C L; Bolli, Roberto

    2015-03-27

    Although numerous preclinical investigations have consistently demonstrated salubrious effects of c-kit(pos) cardiac cells administered after myocardial infarction, the mechanism of action remains highly controversial. We and others have found little or no evidence that these cells differentiate into mature functional cardiomyocytes, suggesting paracrine effects. In this review, we propose a new paradigm predicated on a comprehensive analysis of the literature, including studies of cardiac development; we have (facetiously) dubbed this conceptual construct "string theory" of c-kit(pos) cardiac cells because it reconciles multifarious and sometimes apparently discrepant results. There is strong evidence that, during development, the c-kit receptor is expressed in different pools of cardiac progenitors (some capable of robust cardiomyogenesis and others with little or no contribution to myocytes). Accordingly, c-kit positivity, in itself, does not define the embryonic origins, lineage capabilities, or differentiation capacities of specific cardiac progenitors. C-kit(pos) cells derived from the first heart field exhibit cardiomyogenic potential during development, but these cells are likely depleted shortly before or after birth. The residual c-kit(pos) cells found in the adult heart are probably of proepicardial origin, possess a mesenchymal phenotype (resembling bone marrow mesenchymal stem/stromal cells), and are capable of contributing significantly only to nonmyocytic lineages (fibroblasts, smooth muscle cells, and endothelial cells). If these 2 populations (first heart field and proepicardium) express different levels of c-kit, the cardiomyogenic potential of first heart field progenitors might be reconciled with recent results of c-kit(pos) cell lineage tracing studies. The concept that c-kit expression in the adult heart identifies epicardium-derived, noncardiomyogenic precursors with a mesenchymal phenotype helps to explain the beneficial effects of c

  16. Strategy Escalation: An emerging paradigm for safe clinical development of T cell gene therapies

    Directory of Open Access Journals (Sweden)

    Junghans Richard

    2010-06-01

    Full Text Available Abstract Gene therapy techniques are being applied to modify T cells with chimeric antigen receptors (CARs for therapeutic ends. The versatility of this platform has spawned multiple options for their application with new permutations in strategies continually being invented, a testimony to the creative energies of many investigators. The field is rapidly expanding with immense potential for impact against diverse cancers. But this rapid expansion, like the Big Bang, comes with a somewhat chaotic evolution of its therapeutic universe that can also be dangerous, as seen by recently publicized deaths. Time-honored methods for new drug testing embodied in Dose Escalation that were suitable for traditional inert agents are now inadequate for these novel "living drugs". In the following, I propose an approach to escalating risk for patient exposures with these new immuno-gene therapy agents, termed Strategy Escalation, that accounts for the molecular and biological features of the modified cells and the methods of their administration. This proposal is offered not as a prescriptive but as a discussion framework that investigators may wish to consider in configuring their intended clinical applications.

  17. A New Paradigm in Cardiac Regeneration: The Mesenchymal Stem Cell Secretome

    Directory of Open Access Journals (Sweden)

    Clara Gallina

    2015-01-01

    Full Text Available The potentialities to apply mesenchymal stem cells (MSCs in regenerative medicine have been extensively studied over the last decades. In the cardiovascular disease (CVD field, MSCs-based therapy is the subject of great expectations. Its therapeutic potential has been already shown in several preclinical models and both the safety and efficacy of MSCs-based therapy are being evaluated in humans. It is now clear that the predominant mechanism by which MSCs participate in heart tissue repair is through a paracrine activity. Via the production of a multitude of trophic factors endowed with different properties, MSCs can reduce tissue injury, protect tissue from further adverse effects, and enhance tissue repair. The present review discusses the current understanding of the MSCs secretome as a therapy for treatment of CVD. We provide insights into the possible employment of the MSCs secretome and their released extracellular vesicles as novel approaches for cardiac regeneration that would have certain advantages over injection of living cells.

  18. A mechanistic paradigm for broad-spectrum antivirals that target virus-cell fusion.

    Directory of Open Access Journals (Sweden)

    Frederic Vigant

    Full Text Available LJ001 is a lipophilic thiazolidine derivative that inhibits the entry of numerous enveloped viruses at non-cytotoxic concentrations (IC50 ≤ 0.5 µM, and was posited to exploit the physiological difference between static viral membranes and biogenic cellular membranes. We now report on the molecular mechanism that results in LJ001's specific inhibition of virus-cell fusion. The antiviral activity of LJ001 was light-dependent, required the presence of molecular oxygen, and was reversed by singlet oxygen ((1O2 quenchers, qualifying LJ001 as a type II photosensitizer. Unsaturated phospholipids were the main target modified by LJ001-generated (1O2. Hydroxylated fatty acid species were detected in model and viral membranes treated with LJ001, but not its inactive molecular analog, LJ025. (1O2-mediated allylic hydroxylation of unsaturated phospholipids leads to a trans-isomerization of the double bond and concurrent formation of a hydroxyl group in the middle of the hydrophobic lipid bilayer. LJ001-induced (1O2-mediated lipid oxidation negatively impacts on the biophysical properties of viral membranes (membrane curvature and fluidity critical for productive virus-cell membrane fusion. LJ001 did not mediate any apparent damage on biogenic cellular membranes, likely due to multiple endogenous cytoprotection mechanisms against phospholipid hydroperoxides. Based on our understanding of LJ001's mechanism of action, we designed a new class of membrane-intercalating photosensitizers to overcome LJ001's limitations for use as an in vivo antiviral agent. Structure activity relationship (SAR studies led to a novel class of compounds (oxazolidine-2,4-dithiones with (1 100-fold improved in vitro potency (IC50<10 nM, (2 red-shifted absorption spectra (for better tissue penetration, (3 increased quantum yield (efficiency of (1O2 generation, and (4 10-100-fold improved bioavailability. Candidate compounds in our new series moderately but significantly (p≤0

  19. Sensitivity and optimization of composite structures using MSC/NASTRAN

    Science.gov (United States)

    Nagendra, Gopal K.; Fleury, Claude

    1987-01-01

    Design sensitivity analysis for composites will soon be available in MSC/NASTRAN. The design variables for composites can be lamina thicknesses, orientation angles, material properties or a combination of all three. With the increasing use of composites in aerospace and automotive industries, this general capability can be used in its own right for carrying out sensitivity analysis of complicated real-life structures. As part of a research effort, the sensitivity analysis was coupled with a general purpose optimizer. This preliminary version of the optimizer is capable of dealing with minimum weight structural design with a rather general design variable linking capability at the element level or system level. Only sizing type of design variables (i.e., lamina thicknesses) can be handled by the optimizer. Test cases were run and validated by comparison with independent finite element packages. The linking of design sensitivity capability for composites in MSC/NASTRAN with an optimizer would give designers a powerful automated tool to carry out practical opitmization design of real-life complicated composite structures.

  20. Sarcomas as a mise en abyme of mesenchymal stem cells: exploiting interrelationships for cell mediated anticancer therapy

    DEFF Research Database (Denmark)

    Burns, Jorge S; Safwat, Akmal; Grisendi, Giulia;

    2012-01-01

    Mise en abyme meaning "placed into abyss or infinite recurrence" is an apt paradigm for the relentless growth of sarcoma cells. Its alternative meaning, "self-reflexive embedding" fits the central role attributed to cancer stem cells (CSCs). Diversely sourced and defined, mesenchymal stem cells...... (MSCs) may be the cells of sarcoma origin, evolve a CSC phenotype and/or contribute to tumor growth through inherent qualities for homing, neovascularization, paracrine cross-feeding, microvesicle secretion, cell fusion, entosis and immune modulation. Exploiting these qualities, MSC expressing modified...

  1. Comprehensive transcriptomic and proteomic characterization of human mesenchymal stem cells reveals source specific cellular markers.

    Science.gov (United States)

    Billing, Anja M; Ben Hamidane, Hisham; Dib, Shaima S; Cotton, Richard J; Bhagwat, Aditya M; Kumar, Pankaj; Hayat, Shahina; Yousri, Noha A; Goswami, Neha; Suhre, Karsten; Rafii, Arash; Graumann, Johannes

    2016-01-01

    Mesenchymal stem cells (MSC) are multipotent cells with great potential in therapy, reflected by more than 500 MSC-based clinical trials registered with the NIH. MSC are derived from multiple tissues but require invasive harvesting and imply donor-to-donor variability. Embryonic stem cell-derived MSC (ESC-MSC) may provide an alternative, but how similar they are to ex vivo MSC is unknown. Here we performed an in depth characterization of human ESC-MSC, comparing them to human bone marrow-derived MSC (BM-MSC) as well as human embryonic stem cells (hESC) by transcriptomics (RNA-seq) and quantitative proteomics (nanoLC-MS/MS using SILAC). Data integration highlighted and validated a central role of vesicle-mediated transport and exosomes in MSC biology and also demonstrated, through enrichment analysis, their versatility and broad application potential. Particular emphasis was placed on comparing profiles between ESC-MSC and BM-MSC and assessing their equivalency. Data presented here shows that differences between ESC-MSC and BM-MSC are similar in magnitude to those reported for MSC of different origin and the former may thus represent an alternative source for therapeutic applications. Finally, we report an unprecedented coverage of MSC CD markers, as well as membrane associated proteins which may benefit immunofluorescence-based applications and contribute to a refined molecular description of MSC. PMID:26857143

  2. 基于MSC POOL实现SERVER容灾的方案研究

    Institute of Scientific and Technical Information of China (English)

    徐萍

    2014-01-01

    本文简要介绍了MSC POOL的演进背景、MSC POOL的概念、容灾,并以新疆移动为例,着重从容灾实现方案的组网、数据准备、实施验证等三方面介绍了基于MSC POOL实现SERVER容灾的方案研究。

  3. Research on Load Transfer Method and Application of MSC Pool%MSC Pool负荷迁移机制及应用研究

    Institute of Scientific and Technical Information of China (English)

    黄华生

    2011-01-01

    针对常规MSC Pool负荷迁移后存在的MSC Pool中各MSC间负荷仍不均衡的情况,创立了基于话务模型的数据预测和多次迭代算法的迁移流程,实现了MSC Pool内的负荷均衡,并通过网管程序实现了负荷不均衡自动监测和负荷自动调整.

  4. M.Sc. in Civil and Structural Engineering

    DEFF Research Database (Denmark)

    Clausen, Johan Christian

    The following pages contain a list of project ideas proposed by the scientific staff at the Department of Civil Engineering, Aalborg University, and a number of companies. Most of the project ideas in this catalogue may form the basis for long and short master projects as well as regular 3rd...... semester projects at the M.Sc. programme in Civil and Structural Engineering. Each project description provides a brief overview of the purpose as well as the main activities. Further, a weighting between theoretical analysis, experimental work and computer modelling has been proposed. Usually...... page. Furthermore, other ideas for projects may be discussed with a potential supervisor. Many private engineering companies have a homepage on which they state that they would like to collaborate with students on a master project....

  5. Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes.

    Science.gov (United States)

    Jossen, Valentin; Schirmer, Cedric; Mostafa Sindi, Dolman; Eibl, Regine; Kraume, Matthias; Pörtner, Ralf; Eibl, Dieter

    2016-01-01

    The potential of human mesenchymal stem cells (hMSCs) for allogeneic cell therapies has created a large amount of interest. However, this presupposes the availability of efficient scale-up procedures. Promising results have been reported for stirred bioreactors that operate with microcarriers. Recent publications focusing on microcarrier-based stirred bioreactors have demonstrated the successful use of Computational Fluid Dynamics (CFD) and suspension criteria (N S1u , N S1) for rapidly scaling up hMSC expansions from mL- to pilot scale. Nevertheless, one obstacle may be the formation of large microcarrier-cell-aggregates, which may result in mass transfer limitations and inhomogeneous distributions of stem cells in the culture broth. The dependence of microcarrier-cell-aggregate formation on impeller speed and shear stress levels was investigated for human adipose derived stromal/stem cells (hASCs) at the spinner scale by recording the Sauter mean diameter (d 32) versus time. Cultivation at the suspension criteria provided d 32 values between 0.2 and 0.7 mm, the highest cell densities (1.25 × 10(6) cells mL(-1) hASCs), and the highest expansion factors (117.0 ± 4.7 on day 7), while maintaining the expression of specific surface markers. Furthermore, suitability of the suspension criterion N S1u was investigated for scaling up microcarrier-based processes in wave-mixed bioreactors for the first time. PMID:26981131

  6. Therapeutic effects of hMAPC and hMSC transplantation after stroke in mice.

    Directory of Open Access Journals (Sweden)

    Silvia Mora-Lee

    Full Text Available Stroke represents an attractive target for stem cell therapy. Although different types of cells have been employed in animal models, a direct comparison between cell sources has not been performed. The aim of our study was to assess the effect of human multipotent adult progenitor cells (hMAPCs and human mesenchymal stem cells (hMSCs on endogenous neurogenesis, angiogenesis and inflammation following stroke. BALB/Ca-RAG 2(-/- γC(-/- mice subjected to FeCl(3 thrombosis mediated stroke were intracranially injected with 2 × 10(5 hMAPCs or hMSCs 2 days after stroke and followed for up to 28 days. We could not detect long-term engraftment of either cell population. However, in comparison with PBS-treated animals, hMSC and hMAPC grafted animals demonstrated significantly decreased loss of brain tissue. This was associated with increased angiogenesis, diminished inflammation and a glial-scar inhibitory effect. Moreover, enhanced proliferation of cells in the subventricular zone (SVZ and survival of newly generated neuroblasts was observed. Interestingly, these neuroprotective effects were more pronounced in the group of animals treated with hMAPCs in comparison with hMSCs. Our results establish cell therapy with hMAPCs and hMSCs as a promising strategy for the treatment of stroke.

  7. Towards an understanding of the structural and functional properties of MscL, a mechanosensitive channel in bacteria

    Science.gov (United States)

    Blount, P.; Sukharev, S. I.; Moe, P. C.; Nagle, S. K.; Kung, C.

    1996-01-01

    Whether it be to sense a touch, arterial pressure, or an osmotic gradient across a cell membrane, essentially all living organisms require the capability of detecting mechanical force. Electrophysiological evidence has suggested that mechanosensitive ion channels play a major role in many systems where mechanical force is detected. But, despite their biological importance, determination of the most basic structural and functional features of mechanosensitive channels has only recently become possible. A gene called mscL, which was isolated from Escherichia coli, was the first gene shown to encode a mechanosensitive channel activity. This channel directly responds to tension in the membrane; no other proteins are required. MscL appears to be a homohexamer of a 136 amino acid polypeptide that is highly alpha helical, contains two transmembrane domains, and has both the amino and carboxyl termini in the cytoplasm. The study of the MscL protein remains, to date, one of the most viable options for understanding the structural and functional characteristics of a mechanosensitive channel.

  8. The ‘devils triangle’ of MSC certification: Balancing credibility, accessibility and continuous improvement

    NARCIS (Netherlands)

    Bush, S.R.; Toonen, H.M.; Oosterveer, P.J.M.; Mol, A.P.J.

    2013-01-01

    The Marine Stewardship Council (MSC) has continued to strengthen its position in the market based on its credibility as a transparent, accountable and science-based third party certification scheme. However, the consolidation of MSC's credibility risks being undermined by the poor representation of

  9. 基于lu_flex的MSC Pool技术分析

    Institute of Scientific and Technical Information of China (English)

    杨波; 樊自甫; 万晓榆

    2008-01-01

    MSC池(MSCin Pool)是由3GPP规范定义的,能优化整个移动网络的组网。本文简要介绍了MSC Pool技术的基本原理及其组网特点,分析了MSC Pool所用到的关键技术(NRI路由机制和负荷分担),重点讨论了核心网D接口信令的流量,根据MSC Pool的技术特点,提出了组网规划的前提条件和规划时需要注意的问题,最后总结了MSC Pool技术的特点,在结论部分给出了MSC Pool可能存在的安全隐患。

  10. Didaktiske paradigmer og refleksion

    DEFF Research Database (Denmark)

    Christensen, Torben Spanget

    2014-01-01

    this article. A possible utilitarian didactical paradigm, already indicated by Krogh as a historical paradigm prominent in our time, is also discussed. It is suggested that reflection could be seen as a normative response to the utilitarian paradigm, and not as a paradigm in its own right. It is concluded...... that reflection must be understood as an overarching cultural phenomenon and a very important qualification of all Nielsen’s paradigms, and also a possible utilitarian paradigm, because it has the potential to add dynamic elements to the more or less static didactic paradigms. Thus the semiotic analysis may...

  11. CNN a paradigm for complexity

    CERN Document Server

    Chua, Leon O

    1998-01-01

    Revolutionary and original, this treatise presents a new paradigm of EMERGENCE and COMPLEXITY, with applications drawn from numerous disciplines, including artificial life, biology, chemistry, computation, physics, image processing, information science, etc.CNN is an acronym for Cellular Neural Networks when used in the context of brain science, or Cellular Nonlinear Networks, when used in the context of emergence and complexity. A CNN is modeled by cells and interactions: cells are defined as dynamical systems and interactions are defined via coupling laws. The CNN paradigm is a universal Tur

  12. LTE网络部署CSFB语音时MSC POOL解决方案研究%Research on MSC POOL Solution to CSFB Voice Deployed in LTE Network

    Institute of Scientific and Technical Information of China (English)

    张红霞

    2014-01-01

    LTE部署初期,运营商通过CSFB技术为LTE用户提供语音业务。现网2G/3G端局采用MSC POOL组网的情况下,部署CSFB功能后引入了一些新问题。基于此,通过调整组网和配置、MSC和MME流程优化等方法来解决,既完成了CSFB功能又体现了MSC POOL组网的优势。%In the early stage of LTE deployment, telecom operator provides voice service to LTE subscribers using CSFB(Circuit Switched Fallback) technology. However, with MSC POOL already applied in current 2G/3G networks, some new problems arise when CSFB technology is introduced. In view of this situations, they are can be solved by adjusting networking and configuration, as well as optimizing MSC and MME flows. Thus, the advantages of both CSFB function and MSC POOL networking are simultaneously implemented.

  13. 包头联通核心网MSC POOL规划案例

    Institute of Scientific and Technical Information of China (English)

    宇文广

    2014-01-01

    通过对MSC POOL原理简要介绍,根据MSC POOL的实施目标及原则,以包头联通网络为例,将包头联通的网络现状作为基础,阐述CS域中MSS设备组POOL的具体实施方案.根据该方案的具体描述可以指导包头联通MSC POOL的建设.

  14. Curriculum (Study Programme) for the M.Sc., Medialogy, at Aalborg University in Copenhagen

    DEFF Research Database (Denmark)

    Serafin, Stefania; Nordahl, Rolf; Lavatino, Salvatore

    2004-01-01

    Defining and describing the education, M.Sc., Medialogy. The curriculum (Study Programme) describes semesters, themes, projectunits, courses and contents of the eduation. offered at Aalborg University in Copenhagen....

  15. Paradigms of polyamory.

    Science.gov (United States)

    Zambrano, M

    1999-01-01

    SUMMARY The paradigm theory of Thomas Kuhn is used as a framework to discuss alternative ways of intimacy. The author discusses the implications of structuring actual lesbian relationships by a paradigm of monogamy among Latin-American women. The author proposes that creating alternative paradigms of multiple relationships would be useful for many lesbians as models for alternative life patterns.

  16. Positioning Theory in Paradigms

    Institute of Scientific and Technical Information of China (English)

    FU Xiao-qiu

    2015-01-01

    This article discusses the importance of theory and paradigm to a researcher. It starts from introducing and analyzing the definition of the two terms, by using the theories in the field of intercultural communication as examples. To a good researcher, he needs not only clarifying the paradigm his research is positioned, but also integrating the theories in his paradigm.

  17. Defending the future: An MSc module in End User Computing Risk Management

    OpenAIRE

    Thorne, Simon

    2010-01-01

    This paper describes the rationale, curriculum and subject matter of a new MSc module being taught on an MSc Finance and Information Management course at the University of Wales Institute in Cardiff. Academic research on spreadsheet risks now has some penetration in academic literature and there is a growing body of knowledge on the subjects of spreadsheet error, human factors, spreadsheet engineering, "best practice", spreadsheet risk management and various techniques used to mitigate spread...

  18. Interdisciplinary MSc and Doctoral Education in Climate System Science at the University of Hamburg

    Science.gov (United States)

    Dilly, Oliver; Stammer, Detlef; Pfeiffer, Eva-Maria

    2010-05-01

    Modern education in climate system sciences is based on a number of disciplines such as meteorology, geophysics, oceanography, geosciences and also economics and social sciences. Facts across these disciplines are required to address the faced key issues related to climate change effectively. Climate experts need to have profound knowledge that can only be achieved in interdisciplinary MSc and PhD programs. In Europe, graduate students who completed a BSc degree are typically proceeding with MSc programs to increase knowledge and qualification. Afterwards, the participation in a doctoral program may follow. Many doctoral programs include courses supporting disciplinary methodological and scientific background in particular. Those courses derive either from advanced MSc programs or specific trainings. Typically, interdisciplinary exchange is difficult to achieve at any stage of disciplinary graduate programs. Recent developments showed the need to educate climate experts in interdisciplinary MSc programs in climate system sciences for both researchers and professionals outside the university. The University of Hamburg offers an interdisciplinary 2-yr MSc program in Integrated System Sciences with 120 ECTS (30 compulsory, 90 eligible) in English language. If the MSc student decides to proceed with a PhD thesis, he/she may not necessarily complete the MSc program but may start to work on a specific and disciplinary doctoral thesis for 3 years. Each doctoral student is guided by an advisory panel (AP) which meets at least bi-annually. The AP consists of a Principal Advisor, a Co-Advisor and a Chair of the panel who come from neighboring disciplines. The structured doctoral program with only 12 CPs includes interdisciplinary compulsory courses and tailor-made eligible expert courses. Summer schools and soft skill courses add to both MSc and doctoral programs. Accordingly, the new graduate school concepts in climate system sciences at the University of Hamburg supports

  19. Stem cell therapy independent of stemness

    OpenAIRE

    Lee, Techung

    2012-01-01

    Mesenchymal stem cell (MSC) therapy is entering a new era shifting the focus from initial feasibility study to optimization of therapeutic efficacy. However, how MSC therapy facilitates tissue regeneration remains incompletely characterized. Consistent with the emerging notion that secretion of multiple growth factors/cytokines (trophic factors) by MSC provides the underlying tissue regenerative mechanism, the recent study by Bai et al demonstrated a critical therapeutic role of MSC-derived h...

  20. Mechanosensitive channels of Escherichia coli: the MscL gene, protein, and activities

    Science.gov (United States)

    Sukharev, S. I.; Blount, P.; Martinac, B.; Kung, C.

    1997-01-01

    Although mechanosensory responses are ubiquitous and diverse, the molecular bases of mechanosensation in most cases remain mysterious MscL, a mechanosensitive channel of large conductance of Escherichia coli and its bacterial homologues are the first and currently only channel molecules shown to directly sense mechanical stretch of the membrane. In response to the tension conveyed via the lipid bilayer, MscL increases its open probability by several orders of magnitude. In the present review we describe the identification, cloning, and first sets of biophysical and structural data on this simplest mechanosensory molecule. We discovered a 2.5-ns mechanosensitive conductance in giant E. coli spheroplasts. Using chromatographies to enrich the target and patch clamp to assay the channel activity in liposome-reconstituted fractions, we identified the MscL protein and cloned the mscL gene. MscL comprises 136 amino acid residues (15 kDa), with two highly hydrophobic regions, and resides in the inner membrane of the bacterium. PhoA-fusion experiments indicate that the protein spans the membrane twice with both termini in the cytoplasm. Spectroscopic techniques show that it is highly helical. Expression of MscL tandems and covalent cross-linking suggest that the active channel complex is a homo-hexamer. We have identified several residues, which when deleted or substituted, affect channel kinetics or mechanosensitivity. Although unique when discovered, highly conserved MscL homologues in both gram-negative and gram-positive bacteria have been found, suggesting their ubiquitous importance among bacteria.

  1. Human Allogeneic Bone Marrow and Adipose Tissue Derived Mesenchymal Stromal Cells Induce CD8+ Cytotoxic T Cell Reactivity

    OpenAIRE

    Roemeling-van Rhijn, Marieke; Reinders, Marlies E.; Franquesa, Marcella; Engela, Anja U; Korevaar, Sander S; Roelofs, Helene; Genever, Paul G; IJzermans, Jan NM; Betjes, Michiel GH; Baan, Carla C; Weimar, Willem; Hoogduijn, Martin J.

    2013-01-01

    Introduction For clinical applications, Mesenchymal Stromal Cells (MSC) can be isolated from bone marrow and adipose tissue of autologous or allogeneic origin. Allogeneic cell usage has advantages but may harbor the risk of sensitization against foreign HLA. Therefore, we evaluated whether bone marrow and adipose tissue-derived MSC are capable of inducing HLA-specific alloreactivity. Methods MSC were isolated from healthy human Bone Marrow (BM-MSC) and adipose tissue (ASC) donors. Peripheral ...

  2. Changing paradigms in cranio-facial regeneration: current and new strategies for the activation of endogenous stem cells

    Directory of Open Access Journals (Sweden)

    Luigi eMele

    2016-02-01

    Full Text Available Craniofacial area represent a unique district of human body characterized by a very high complexity of tissues, innervation and vascularization, and being deputed to many fundamental function such as eating, speech, expression of emotions, delivery of sensations such as taste, sight and earing. For this reasons, tissue loss in this area following trauma or for example oncologic resection, have a tremendous impact on patients’ quality of life. In the last 20 years regenerative medicine has emerged as one of the most promising approach to solve problem related to trauma, tissue loss, organ failure etc. One of the most powerful tools to be used for tissue regeneration is represented by stem cells, which have been successfully implanted in different tissue/organs with exciting results. Nevertheless both autologous and allogeneic stem cell transplantation raise many practical and ethical concerns that make this approach very difficult to apply in clinical practice. For this reason different cell free approaches have been developed aiming to the mobilization, recruitment and activation of endogenous stem cells into the injury site avoiding exogenous cells implant but instead stimulating patients’ own stem cells to repair the lesion. To this aim many strategies have been used including functionalized bioscaffold, controlled release of stem cell chemoattractants, growth factors, BMPs, Platelet–Rich-Plasma and other new strategies such as ultrasound wave and laser are just being proposed. Here we review all the current and new strategies used for activation and mobilization of endogenous stem cells in the regeneration of craniofacial tissue.

  3. Changing Paradigms in Cranio-Facial Regeneration: Current and New Strategies for the Activation of Endogenous Stem Cells

    Science.gov (United States)

    Mele, Luigi; Vitiello, Pietro Paolo; Tirino, Virginia; Paino, Francesca; De Rosa, Alfredo; Liccardo, Davide; Papaccio, Gianpaolo; Desiderio, Vincenzo

    2016-01-01

    Craniofacial area represent a unique district of human body characterized by a very high complexity of tissues, innervation and vascularization, and being deputed to many fundamental function such as eating, speech, expression of emotions, delivery of sensations such as taste, sight, and earing. For this reasons, tissue loss in this area following trauma or for example oncologic resection, have a tremendous impact on patients' quality of life. In the last 20 years regenerative medicine has emerged as one of the most promising approach to solve problem related to trauma, tissue loss, organ failure etc. One of the most powerful tools to be used for tissue regeneration is represented by stem cells, which have been successfully implanted in different tissue/organs with exciting results. Nevertheless, both autologous and allogeneic stem cell transplantation raise many practical and ethical concerns that make this approach very difficult to apply in clinical practice. For this reason different cell free approaches have been developed aiming to the mobilization, recruitment, and activation of endogenous stem cells into the injury site avoiding exogenous cells implant but instead stimulating patients' own stem cells to repair the lesion. To this aim many strategies have been used including functionalized bioscaffold, controlled release of stem cell chemoattractants, growth factors, BMPs, Platelet–Rich-Plasma, and other new strategies such as ultrasound wave and laser are just being proposed. Here we review all the current and new strategies used for activation and mobilization of endogenous stem cells in the regeneration of craniofacial tissue. PMID:26941656

  4. Changing Paradigms in Cranio-Facial Regeneration: Current and New Strategies for the Activation of Endogenous Stem Cells.

    Science.gov (United States)

    Mele, Luigi; Vitiello, Pietro Paolo; Tirino, Virginia; Paino, Francesca; De Rosa, Alfredo; Liccardo, Davide; Papaccio, Gianpaolo; Desiderio, Vincenzo

    2016-01-01

    Craniofacial area represent a unique district of human body characterized by a very high complexity of tissues, innervation and vascularization, and being deputed to many fundamental function such as eating, speech, expression of emotions, delivery of sensations such as taste, sight, and earing. For this reasons, tissue loss in this area following trauma or for example oncologic resection, have a tremendous impact on patients' quality of life. In the last 20 years regenerative medicine has emerged as one of the most promising approach to solve problem related to trauma, tissue loss, organ failure etc. One of the most powerful tools to be used for tissue regeneration is represented by stem cells, which have been successfully implanted in different tissue/organs with exciting results. Nevertheless, both autologous and allogeneic stem cell transplantation raise many practical and ethical concerns that make this approach very difficult to apply in clinical practice. For this reason different cell free approaches have been developed aiming to the mobilization, recruitment, and activation of endogenous stem cells into the injury site avoiding exogenous cells implant but instead stimulating patients' own stem cells to repair the lesion. To this aim many strategies have been used including functionalized bioscaffold, controlled release of stem cell chemoattractants, growth factors, BMPs, Platelet-Rich-Plasma, and other new strategies such as ultrasound wave and laser are just being proposed. Here we review all the current and new strategies used for activation and mobilization of endogenous stem cells in the regeneration of craniofacial tissue. PMID:26941656

  5. Improving the Design of a MscL-Based Triggered Nanovalve

    Directory of Open Access Journals (Sweden)

    Paul Blount

    2013-03-01

    Full Text Available The mechanosensitive channel of large conductance, MscL, has been proposed as a triggered nanovalve to be used in drug release and other nanodevices. It is a small homopentameric bacterial protein that has the largest gated pore known: greater than 30 Å. Large molecules, even small proteins can be released through MscL. Although MscL normally gates in response to membrane tension, early studies found that hydrophilic or charged residue substitutions near the constriction of the channel leads to pore opening. Researchers have successfully changed the modality of MscL to open to stimuli such as light by chemically modifying a single residue, G22, within the MscL pore. Here, by utilizing in vivo, liposome efflux, and patch clamp assays we compared modification of G22 with that of another neighboring residue, G26, and demonstrate that modifying G26 may be a better choice for triggered nanovalves used for triggered vesicular release of compounds.

  6. Chimeras Reveal a Single Lipid-Interface Residue that Controls MscL Channel Kinetics as well as Mechanosensitivity

    Directory of Open Access Journals (Sweden)

    Li-Min Yang

    2013-02-01

    Full Text Available MscL, the highly conserved bacterial mechanosensitive channel of large conductance, serves as an osmotic “emergency release valve,” is among the best-studied mechanosensors, and is a paradigm of how a channel senses and responds to membrane tension. Although all homologs tested thus far encode channel activity, many show functional differences. We tested Escherichia coli and Staphylococcus aureus chimeras and found that the periplasmic region of the protein, particularly E. coli I49 and the equivalent S. aureus F47 at the periplasmic lipid-aqueous interface of the first transmembrane domain, drastically influences both the open dwell time and the threshold of channel opening. One mutant shows a severe hysteresis, confirming the importance of this residue in determining the energy barriers for channel gating. We propose that this site acts similarly to a spring for a clasp knife, adjusting the resistance for obtaining and stabilizing an open or closed channel structure.

  7. Effects of high glucose on mesenchymal stem cell proliferation and differentiation

    International Nuclear Information System (INIS)

    High glucose (HG) concentrations impair cellular functions and induce apoptosis. Exposition of mesenchymal stem cells (MSC) to HG was reported to reduce colony forming activity and induce premature senescence. We characterized the effects of HG on human MSC in vitro using telomerase-immortalized MSC (hMSC-TERT) and primary MSC (hMSC). HG (25 mM) enhanced hMSC-TERT proliferation in long-term studies in contrast to hMSC where proliferation was unchanged. Thioredoxin-interacting protein, which is involved in apoptosis regulation, was stimulated by glucose in hMSC-TERT. However, apoptosis was not influenced by HG in both cell types. MSC treatment with HG favored osteogenic differentiation. MSC are resistant to HG toxicity, depending on the stemness of MSC. Proliferation and osteogenic differentiation are stimulated by HG. Effects of HG on the transient amplifying compartment of MSC may differ from those in mature cells. Further research is needed to unravel the molecular mechanisms of HG resistance of MSC

  8. Targeting P38 Pathway Regulates Bony Formation via MSC Recruitment during Mandibular Distraction Osteogenesis in Rats

    Science.gov (United States)

    Yang, Zi-hui; Wu, Bao-lei; Ye, Chen; Jia, Sen; Yang, Xin-jie; Hou, Rui; Lei, De-lin; Wang, Lei

    2016-01-01

    Distraction osteogenesis (DO) is a widely used self-tissue engineering. However, complications and discomfort due to the long treatment period are still the bottleneck of DO. Novel strategies to accelerate bone formation in DO are still needed. P38 is capable of regulating the osteogenic differentiation of both mesenchymal stem cells (MSCs) and osteoblasts, which are crucial to bone regeneration. However, it is not clear whether targeting p38 could regulate bony formation in DO. The purpose of the current work was to investigate the effects of local application of either p38 agonist anisomycin or p38 inhibitor SB203580 in a rat model of DO. 30 adult rats were randomly divided into 3 groups: (A) rats injected with DMSO served as the control group; (B) rats injected with p38 agonist anisomycin; (C) rats injected with p38 inhibitor SB203580. All the rats were subjected to mandibular distraction and the injection was performed daily during this period. The distracted mandibles were harvested on days 15 and 30 after surgery and subjected to the following analysis. Micro-computed tomography and histological evaluation results showed that local application of p38 agonist anisomycin increased new bone formation in DO, whereas p38 inhibitor SB203580 decreased it. Immunohistochemical analysis suggested that anisomycin promoted MSC recruitment in the distraction gap. In conclusion, this study demonstrated that local application of p38 agonist anisomycin can increase new bone formation during DO. This study may lead to a novel cell-based strategy for the improvement of bone regeneration. PMID:27766028

  9. M-Learning: A New Paradigm of Learning Mathematics in Malaysia

    OpenAIRE

    Saipunidzam Mahamad; Mohammad Noor Ibrahim; Shakirah Mohd Taib

    2010-01-01

    M-Learning is a new learning paradigm of the new social structure with mobile and wireless technologies.Smart school is one of the four flagship applications for Multimedia Super Corridor (MSC) under Malaysian government initiative to improve education standard in the country. With the advances of mobile devices technologies, mobile learning could help the government in realizing the initiative. This paper discusses the prospect of implementing mobile learning for primary school students. It ...

  10. Defending the future: An MSc module in End User Computing Risk Management

    CERN Document Server

    Thorne, Simon

    2010-01-01

    This paper describes the rationale, curriculum and subject matter of a new MSc module being taught on an MSc Finance and Information Management course at the University of Wales Institute in Cardiff. Academic research on spreadsheet risks now has some penetration in academic literature and there is a growing body of knowledge on the subjects of spreadsheet error, human factors, spreadsheet engineering, "best practice", spreadsheet risk management and various techniques used to mitigate spreadsheet errors. This new MSc module in End User Computing Risk Management is an attempt to pull all of this research and practitioner experience together to arm the next generation of finance spreadsheet champions with the relevant knowledge, techniques and critical perspective on an emerging discipline.

  11. Effect of Intrinsic Noise on the Phenotype of Cell Populations Featuring Solution Multiplicity: An Artificial lac Operon Network Paradigm.

    Directory of Open Access Journals (Sweden)

    Ioannis G Aviziotis

    Full Text Available Heterogeneity in cell populations originates from two fundamentally different sources: the uneven distribution of intracellular content during cell division, and the stochastic fluctuations of regulatory molecules existing in small amounts. Discrete stochastic models can incorporate both sources of cell heterogeneity with sufficient accuracy in the description of an isogenic cell population; however, they lack efficiency when a systems level analysis is required, due to substantial computational requirements. In this work, we study the effect of cell heterogeneity in the behaviour of isogenic cell populations carrying the genetic network of lac operon, which exhibits solution multiplicity over a wide range of extracellular conditions. For such systems, the strategy of performing solely direct temporal solutions is a prohibitive task, since a large ensemble of initial states needs to be tested in order to drive the system--through long time simulations--to possible co-existing steady state solutions. We implement a multiscale computational framework, the so-called "equation-free" methodology, which enables the performance of numerical tasks, such as the computation of coarse steady state solutions and coarse bifurcation analysis. Dynamically stable and unstable solutions are computed and the effect of intrinsic noise on the range of bistability is efficiently investigated. The results are compared with the homogeneous model, which neglects all sources of heterogeneity, with the deterministic cell population balance model, as well as with a stochastic model neglecting the heterogeneity originating from intrinsic noise effects. We show that when the effect of intrinsic source of heterogeneity is intensified, the bistability range shifts towards higher extracellular inducer concentration values.

  12. An Integrative Paradigm

    Science.gov (United States)

    Hammack, Phillip L.

    2005-01-01

    Through the application of life course theory to the study of sexual orientation, this paper specifies a new paradigm for research on human sexual orientation that seeks to reconcile divisions among biological, social science, and humanistic paradigms. Recognizing the historical, social, and cultural relativity of human development, this paradigm…

  13. MSC POOL相邻池区切换自动均衡实现

    Institute of Scientific and Technical Information of China (English)

    陈鑫

    2014-01-01

    本文针对MSC POOL大规模组网部署后出现的相邻池区间跨POOL切换不均衡导致用户分布不均匀、话务不均衡问题,介绍了如何实现跨POOL切换的自动均衡、可控、可调,对MSC POOL多池区组网规划优化有一定参考应用价值。

  14. ANALYSIS WITH MSC ADAMS OF A 5-FINGER AND 3-PHALANX /FINGER UNDER-ACTUATEDMECHANICAL HAND

    Directory of Open Access Journals (Sweden)

    Gheorghe POPESCU

    2013-05-01

    Full Text Available This paper studies the analysis with MSC ADAMS of a 5-fingered and 3-phalanx/finger underactuatedmechanical hand, designed by the author to work on industrial robots. Moreover, in order to increasegrasping safety in the automated handling process, the author has fitted each finger with a locking sequence inthe final phase of grasping. Thus, the mechanism of mechanical hand is considered to be a mechanical systemand is treated like a set of rigid bodies connected by mechanical linkages and elastic elements. To model andsimulate this mechanism with MSC ADAMS programme, the author covered the following stages: constructionof the model, testing-simulation, validation, finishing, parameterization, and optimization

  15. Reimplementing the Mathematical Subject Classification (MSC) as a Linked Open Dataset

    CERN Document Server

    Lange, Christoph; Dimou, Anastasia; Bratsas, Charalampos; Corneli, Joseph; Sperber, Wolfram; Kohlhase, Michael; Antoniou, Ioannis

    2012-01-01

    The Mathematics Subject Classification (MSC) is a widely used scheme for classifying documents in mathematics by subject. Its traditional, idiosyncratic conceptualization and representation makes the scheme hard to maintain and requires custom implementations of search, query and annotation support. This limits uptake e.g. in semantic web technologies in general and the creation and exploration of connections between mathematics and related domains (e.g. science) in particular. This paper presents the new official implementation of the MSC2010 as a Linked Open Dataset, building on SKOS (Simple Knowledge Organization System). We provide a brief overview of the dataset's structure, its available implementations, and first applications.

  16. Supervising M.Sc. Students working in the 100 Gigabit Ethernet field using OPNET Modeler

    DEFF Research Database (Denmark)

    Ruepp, Sarah Renée; Berger, Michael Stübert; Wessing, Henrik

    2010-01-01

    This paper deals with supervision methods for M.Sc. students who are using OPNET Modeler for their thesis work within the field of 100 Gigabit Ethernet. We detail how we use OPNET Modeler in our M.Sc. projects at the Technical University of Denmark. In particular, we discuss on how we teach...... students to learn OPNET independently and in a short timeframe, and we outline what students find challenging and rewarding by using OPNET Modeler. Furthermore, we show some cases on how OPNET was applied in specific projects within the field of 100 Gigabit Ethernet....

  17. Education of MSc and PhD Students in Fluid Power and Mechatronics at DTU

    DEFF Research Database (Denmark)

    Conrad, Finn

    1996-01-01

    The paper deals with education of MSc and PhD students in engineering areas fluid power and mechatronics at the Technical Univ of Denmark, DTU, Lyngby. The new education structure and programs for MSc and PhD students adapted to the change and development of technologies. Focus is on two of twenty...... engineering profilies:(1) Engineeing Design and Product Development and (2)Control Engineering which give possibilitie for specialisation in fluid power and mechatronics design and productdevelopment. Synthesis, design and self-learning competency have a high priority taking the importance of training...

  18. Further Developments on Optimum Structural Design Using MSC/Nastran and Sequential Quadratic Programming

    DEFF Research Database (Denmark)

    Holzleitner, Ludwig

    1996-01-01

    This work is closely connected to the paper: K.G. MAHMOUD, H.W. ENGL and HOLZLEITNER: "OPTIMUM STRUCTURAL DESIGN USING MSC/NASTRAN AND SEQUENTIAL QUADRATIC PROGRAMMING", Computers & Structures, Vol. 52, No. 3, pp. 437-447, (1994). In contrast to that paper, where thickness optimization is described...... analysis and gradient calculation are used, together with sequential quadratic programming with an active set strategy for optimization. The optimization and sensitivity analysis modules are efficiently coupled with MSC/NASTRAN using DMAP (direct matrix abstraction program) statements. To demonstrate...

  19. Heparin-induced conformational changes of fibronectin within the extracellular matrix promote hMSC osteogenic differentiation.

    Science.gov (United States)

    Li, Bojun; Lin, Zhe; Mitsi, Maria; Zhang, Yang; Vogel, Viola

    2015-01-01

    An increasing body of evidence suggests important roles of extracellular matrix (ECM) in regulating stem cell fate. This knowledge can be exploited in tissue engineering applications for the design of ECM scaffolds appropriate to direct stem cell differentiation. By probing the conformation of fibronectin (Fn) using fluorescence resonance energy transfer (FRET), we show here that heparin treatment of the fibroblast-derived ECM scaffolds resulted in more extended conformations of fibrillar Fn in ECM. Since heparin is a highly negatively charged molecule while fibronectin contains segments of positively charged modules, including FnIII13, electrostatic interactions between Fn and heparin might interfere with residual quaternary structure in relaxed fibronectin fibers thereby opening up buried sites. The conformation of modules FnIII12-14 in particular, which contain one of the heparin binding sites as well as binding sites for many growth factors, may be activated by heparin, resulting in alterations in growth factor binding to Fn. Indeed, upregulated osteogenic differentiation was observed when hMSCs were seeded on ECM scaffolds that had been treated with heparin and were subsequently chemically fixed. In contrast, either rigidifying relaxed fibers by fixation alone, or heparin treatment without fixation had no effect. We hypothesize that fibronectin's conformations within the ECM are activated by heparin such as to coordinate with other factors to upregulate hMSC osteogenic differentiation. Thus, the conformational changes of fibronectin within the ECM could serve as a 'converter' to tune hMSC differentiation in extracellular matrices. This knowledge could also be exploited to promote osteogenic stem cell differentiation on biomedical surfaces. PMID:26214191

  20. 肿瘤干细胞理论的演变%Evolution of Cancer Stem Cell Paradigm

    Institute of Scientific and Technical Information of China (English)

    张雁

    2012-01-01

    肿瘤干细胞(CSC)是存存于肿瘤组织或肿瘤细胞群中具有干细胞特性的亚群.CSC具有自我更新和分化能力,可以分化为特性各异的细胞.CSC因其强大的起始肿瘤能力和抵抗治疗的特性而成为关注的焦点.肿瘤干细胞理论从起初的单向等级分化模式,发展到现在的随机和等级分化交互模式,较好地解释了肿瘤在形态和功能方面的多样性,是研究肿瘤的发生和发展的理想模型.本文通过对近年来在肿瘤干细胞研究领域的部分卓越成就的解析,阐述了肿瘤干细胞在分化模式、微环境调控和动态变化等方面的特性.%Cancer stem cells (CSC) are a subset of cancer cells that share the characteristics of self-renewal capacity and multipotency with stem cells. CSC produces daughter cells with differential nature and thus contributes to tumor. The presence of CSC is associated with tumor initiation and therapy-resistance. The hierarchical and stochastic CSC model can explain the phenotypic and functional heterogeneity in various types of cancer. In this paper, recent excellent observations in CSC, including cell-lineage, regulation of microenvironment and dynamic equilibrium between CSC and non-CSC are reviewed.

  1. Microvesicles from brain-extract—treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke

    Science.gov (United States)

    Lee, Ji Yong; Kim, Eiru; Choi, Seong-Mi; Kim, Dong-Wook; Kim, Kwang Pyo; Lee, Insuk; Kim, Han-Soo

    2016-01-01

    Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract—treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract—treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury. PMID:27609711

  2. Paracrine Mechanisms of Mesenchymal Stem Cells in Tissue Repair.

    Science.gov (United States)

    Gnecchi, Massimiliano; Danieli, Patrizia; Malpasso, Giuseppe; Ciuffreda, Maria Chiara

    2016-01-01

    Tissue regeneration from transplanted mesenchymal stromal cells (MSC) either through transdifferentiation or cell fusion was originally proposed as the principal mechanism underlying their therapeutic action. However, several studies have now shown that both these mechanisms are very inefficient. The low MSC engraftment rate documented in injured areas also refutes the hypothesis that MSC repair tissue damage by replacing cell loss with newly differentiated cells. Indeed, despite evidence of preferential homing of MSC to the site of myocardial ischemia, exogenously administered MSC show poor survival and do not persist in the infarcted area. Therefore, it has been proposed that the functional benefits observed after MSC transplantation in experimental models of tissue injury might be related to the secretion of soluble factors acting in a paracrine fashion. This hypothesis is supported by pre-clinical studies demonstrating equal or even improved organ function upon infusion of MSC-derived conditioned medium (MSC-CM) compared with MSC transplantation. Identifying key MSC-secreted factors and their functional role seems a reasonable approach for a rational design of nextgeneration MSC-based therapeutics. Here, we summarize the major findings regarding both different MSC-mediated paracrine actions and the identification of paracrine mediators. PMID:27236669

  3. Current view of mesenchymal stem cells biology (brief review

    Directory of Open Access Journals (Sweden)

    Maslova O. A.

    2012-06-01

    Full Text Available Although mesenchymal stem cells (MSC are in a focus of attention, some aspects of their biology are still unclear. This paper is a review of current research on MSC biology. The use of MSC in regenerative medicine is also briefly discussed.

  4. Post-thaw non-cultured and post-thaw cultured equine cord blood mesenchymal stromal cells equally suppress lymphocyte proliferation in vitro.

    Directory of Open Access Journals (Sweden)

    Lynn B Williams

    Full Text Available Multipotent mesenchymal stromal cells (MSC are receiving increased attention for their non-progenitor immunomodulatory potential. Cryopreservation is commonly used for long-term storage of MSC. Post-thaw MSC proliferation is associated with a lag-phase in vitro. How this lag-phase affect MSC immunomodulatory properties is unknown. We hypothesized that in vitro there is no difference in lymphocyte suppression potential between quick-thawed cryopreserved equine cord blood (CB MSC immediately included in mixed lymphocyte reaction (MLR and same MSC allowed post-thaw culture time prior to inclusion in MLR. Cryopreserved CB-MSC from five unrelated foals were compared using two-way MLR. For each of the five unrelated MSC cultures, paired MLR assays of MSC allowed five days of post-thaw culture and MSC included in MLR assay immediately post-thawing were evaluated. We report no difference in the suppression of lymphocyte proliferation by CB-MSC that had undergone post-thaw culture and MSC not cultured post-thaw (p<0.0001. Also, there was no inter-donor variability between the lymphocyte suppressive properties of MSC harvested from the five different donors (p = 0.13. These findings suggest that cryopreserved CB-MSC may have clinical utility immediately upon thawing. One implication hereof is the possibility of using cryopreserved CB-MSC at third party locations without the need for cell culture equipment or competencies.

  5. Comparison of composite rotor blade models: A coupled-beam analysis and an MSC/NASTRAN finite-element model

    Science.gov (United States)

    Hodges, Robert V.; Nixon, Mark W.; Rehfield, Lawrence W.

    1987-01-01

    A methodology was developed for the structural analysis of composite rotor blades. This coupled-beam analysis is relatively simple to use compared with alternative analysis techniques. The beam analysis was developed for thin-wall single-cell rotor structures and includes the effects of elastic coupling. This paper demonstrates the effectiveness of the new composite-beam analysis method through comparison of its results with those of an established baseline analysis technique. The baseline analysis is an MSC/NASTRAN finite-element model built up from anisotropic shell elements. Deformations are compared for three linear static load cases of centrifugal force at design rotor speed, applied torque, and lift for an ideal rotor in hover. A D-spar designed to twist under axial loading is the subject of the analysis. Results indicate the coupled-beam analysis is well within engineering accuracy.

  6. Cerebral transplantation of encapsulated mesenchymal stem cells improves cellular pathology after experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Heile, Anna M B; Wallrapp, Christine; Klinge, Petra M;

    2009-01-01

    PURPOSE: "Naked" human mesenchymal stem cells (MSC) are neuro-protective in experimental brain injury (TBI). In a controlled cortical impact (CCI) rat model, we investigated whether encapsulated MSC (eMSC) act similarly, and whether efficacy is augmented using cells transfected to produce the neu...

  7. Studies on sensitivity to tension and gating pathway of MscL by molecular dynamic simulation

    Institute of Scientific and Technical Information of China (English)

    Jun-Yu Xie; Guang-Hong Ding

    2013-01-01

    Mechanosensitive (MS) ion channels play an important role in various physiological processes.Although the determination of the structure of mechanosensitive channel of large conductance (MscL) makes the simulation study possible,it has not so far been possible to directly simulate the gating mechanism of MscL in atomic detail.In this article,MscL has been studied via molecular dynamic (MD)simulations to gain a detailed description of the sensitivity to lateral tension and the gating pathway.MscL undergoes conformational rearrangement in sustaining lateral tension,and the open state is obtained when 2.0 MPa lateral tension is directly applied on the pure protein.During the opening process,Loop region responds to tension first,and the mechanical sensitivity is followed by S1 domain.Transmembrane (TM) bundle is the key position for channel opening,and the motion of TM1 helices finally realizes the significant expansion of the constricted gating pore.C-terminus domain presents expansion later during the TM opening.In our study,return of the whole protein to the initial closed state is achieved only in the early opening stage.During the relaxation from the open state,the TM helices are the most mobile domain,which is different from the opening process.

  8. Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations

    NARCIS (Netherlands)

    Deplazes, Evelyne; Louhivuori, Martti; Jayatilaka, Dylan; Marrink, Siewert J.; Corry, Ben; Elofsson, Arne

    2012-01-01

    The mechanosensitive channel of large conductance (MscL) has become a model system in which to understand mechanosensation, a process involved in osmoregulation and many other physiological functions. While a high resolution closed state structure is available, details of the open structure and the

  9. New MSc programme in Sustainable Energy at Risø DTU

    DEFF Research Database (Denmark)

    Ryde, M.

    2007-01-01

    In September 2008, the fi rst batch of students will start a new MSc programme which is based at Risø DTU. It is a two-year study programme, so the students will be well into their studies when the UN’s climate conference is held in Copenhagen in 2009...

  10. Competencies of BSc and MSc programmes in electrical engineering and student portfolios

    NARCIS (Netherlands)

    Mouthaan, Ton J.; Brink, R.W.; Vos, H.

    2002-01-01

    General goals of a BSc and MSc in electrical engineering are formulated, leading to a 'mission' statement clarifying the rationale behind the programmes in relation to the needs of society. These goals are made operational in terms of competencies that engineers educated through our programmes are r

  11. Paradigms for machine learning

    Science.gov (United States)

    Schlimmer, Jeffrey C.; Langley, Pat

    1991-01-01

    Five paradigms are described for machine learning: connectionist (neural network) methods, genetic algorithms and classifier systems, empirical methods for inducing rules and decision trees, analytic learning methods, and case-based approaches. Some dimensions are considered along with these paradigms vary in their approach to learning, and the basic methods are reviewed that are used within each framework, together with open research issues. It is argued that the similarities among the paradigms are more important than their differences, and that future work should attempt to bridge the existing boundaries. Finally, some recent developments in the field of machine learning are discussed, and their impact on both research and applications is examined.

  12. Hepatoma SK Hep-1 cells exhibit characteristics of oncogenic mesenchymal stem cells with highly metastatic capacity.

    Directory of Open Access Journals (Sweden)

    Jong Ryeol Eun

    Full Text Available BACKGROUND: SK Hep-1 cells (SK cells derived from a patient with liver adenocarcinoma have been considered a human hepatoma cell line with mesenchymal origin characteristics, however, SK cells do not express liver genes and exhibit liver function, thus, we hypothesized whether mesenchymal cells might contribute to human liver primary cancers. Here, we characterized SK cells and its tumourigenicity. METHODS AND PRINCIPAL FINDINGS: We found that classical mesenchymal stem cell (MSC markers were presented on SK cells, but endothelial marker CD31, hematopoietic markers CD34 and CD45 were negative. SK cells are capable of differentiate into adipocytes and osteoblasts as adipose-derived MSC (Ad-MSC and bone marrow-derived MSC (BM-MSC do. Importantly, a single SK cell exhibited a substantial tumourigenicity and metastatic capacity in immunodefficient mice. Metastasis not only occurred in circulating organs such as lung, liver, and kidneys, but also in muscle, outer abdomen, and skin. SK cells presented greater in vitro invasive capacity than those of Ad-MSC and BM-MSC. The xenograft cells from subcutaneous and metastatic tumors exhibited a similar tumourigenicity and metastatic capacity, and showed the same relatively homogenous population with MSC characteristics when compared to parental SK cells. SK cells could unlimitedly expand in vitro without losing MSC characteristics, its tumuorigenicity and metastatic capacity, indicating that SK cells are oncogenic MSC with enhanced self-renewal capacity. We believe that this is the first report that human MSC appear to be transformed into cancer stem cells (CSC, and that their derivatives also function as CSCs. CONCLUSION: Our findings demonstrate that SK cells represent a transformation mechanism of normal MSC into an enhanced self-renewal CSC with metastasis capacity, SK cells and their xenografts represent a same relative homogeneity of CSC with substantial metastatic capacity. Thus, it represents a

  13. Simulation of Air Suspension and Full-vehicle with MSC Adams/Car%基于MSC Adams/Car的空气悬架及整车仿真

    Institute of Scientific and Technical Information of China (English)

    王登峰; 郎锡泽; 马天飞

    2006-01-01

    利用MSC Adams/Car软件建立载货汽车后空气悬架系统多体动力学模型,仿真计算了悬架垂直刚度特性,证明模型的正确性. 建立Adams/Car的整车模型,进行稳态回转试验的仿真分析. 将仿真结果与道路试验结果进行比较,验证虚拟样机模型的正确性.

  14. Characterization of Human Mesenchymal Stem Cells from Ewing Sarcoma Patients. Pathogenetic Implications

    Science.gov (United States)

    Amaral, Ana Teresa; Manara, Maria Cristina; Berghuis, Dagmar; Ordóñez, José Luis; Biscuola, Michele; Lopez-García, Maria Angeles; Osuna, Daniel; Lucarelli, Enrico; Alviano, Francesco; Lankester, Arjan; Scotlandi, Katia; de Álava, Enrique

    2014-01-01

    Background Ewing Sarcoma (EWS) is a mesenchymal-derived tumor that generally arises in bone and soft tissue. Intensive research regarding the pathogenesis of EWS has been insufficient to pinpoint the early events of Ewing sarcomagenesis. However, the Mesenchymal Stem Cell (MSC) is currently accepted as the most probable cell of origin. Materials and Methods In an initial study regarding a deep characterization of MSC obtained specifically from EWS patients (MSC-P), we compared them with MSC derived from healthy donors (MSC-HD) and EWS cell lines. We evaluated the presence of the EWS-FLI1 gene fusion and EWSR1 gene rearrangements in MSC-P. The presence of the EWS transcript was confirmed by q-RT-PCR. In order to determine early events possibly involved in malignant transformation, we used a multiparameter quantitative strategy that included both MSC immunophenotypic negative/positive markers, and EWS intrinsic phenotypical features. Markers CD105, CD90, CD34 and CD45 were confirmed in EWS samples. Results We determined that MSC-P lack the most prevalent gene fusion, EWSR1-FLI1 as well as EWSR1 gene rearrangements. Our study also revealed that MSC-P are more alike to MSC-HD than to EWS cells. Nonetheless, we also observed that EWS cells had a few overlapping features with MSC. As a relevant example, also MSC showed CD99 expression, hallmark of EWS diagnosis. However, we observed that, in contrast to EWS cells, MSC were not sensitive to the inhibition of CD99. Conclusions In conclusion, our results suggest that MSC from EWS patients behave like MSC-HD and are phenotypically different from EWS cells, thus raising important questions regarding MSC role in sarcomagenesis. PMID:24498265

  15. The MOND paradigm

    OpenAIRE

    Milgrom, Mordehai

    2008-01-01

    I review briefly different aspects of the MOND paradigm, with emphasis on phenomenology, epitomized here by many MOND laws of galactic motion--analogous to Kepler's laws of planetary motion. I then comment on the possible roots of MOND in cosmology, possibly the deepest and most far reaching aspect of MOND. This is followed by a succinct account of existing underlying theories. I also reflect on the implications of MOND's successes for the dark matter (DM) paradigm: MOND predictions imply tha...

  16. Development (Paradigm) Failures

    OpenAIRE

    Hodler, Roland

    2011-01-01

    Over time the international development community has advocated various development paradigms, but countries following these paradigms have often performed poorly. I provide an explanation for this poor performance. In my model the political leader of a developing country chooses a policy and whether to implement it in an honest or corrupt manner. These choices affect domestic production and aid inflows. Production is high when productive capacity is high, and when the policy is appropriate i...

  17. Photo-irradiation paradigm: Mapping a remarkable facile technique used for advanced drug, gene and cell delivery.

    Science.gov (United States)

    Shaker, Mohamed A; Younes, Husam M

    2015-11-10

    Undoubtedly, the progression of photo-irradiation technique has provided a smart engineering tool for the state-of-the-art biomaterials that guide the biomedical and therapeutic domains for promoting the modern pharmaceutical industry. Many investigators had exploited such a potential technique to create/ameliorate numerous pharmaceutical carriers. These carriers show promising applications that vary from small drug to therapeutic protein delivery and from gene to living cell encapsulation design. Harmony between the properties of precisely engineered precursors and the formed network structure broadens the investigator's intellect for both brilliant creations and effective applications. As well, controlling photo-curing at the formulation level, through manipulating the absorption of light stimuli, photoinitiator system and photo-responsive precursor, facilitates the exploration of novel distinctive biomaterials. Discussion of utilizing different photo-curing procedures in designing/formulation of different pharmaceutical carriers is the main emphasis of this review. In addition, recent applications of these intelligent techniques in targeted, controlled, and sustained drug delivery with understanding of photo-irradiation concept and mechanism are illustrated.

  18. Spot14/Spot14R expression may be involved in MSC adipogenic differentiation in patients with adolescent idiopathic scoliosis

    Science.gov (United States)

    WANG, QIFEI; YANG, JUNLIN; LIN, XIANG; HUANG, ZIFANG; XIE, CHAOFAN; FAN, HENGWEI

    2016-01-01

    The aim of the present study was to evaluate the different expression levels of thyroid hormone responsive (THRSP; Spot14)/S14 related, Mig12 (S14R) during bone marrow mesenchymal stem cell (BM-MSC) adipogenesis in adolescent idiopathic scoliosis (AIS) patients. MSCs were retrospectively isolated from AIS patients and controls, and adipogenic differentiation was induced. Total RNA was extracted for Affymetrix 3′-IVT expression profiling microarrays and compared with the results from healthy controls. The results were confirmed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) validation and the protein expression levels of Spot14 and its paralogous gene S14R by western blotting and immunohistochemistry. A total of 300 significantly altered mRNAs were detected (111 upregulated and 189 downregulated) and confirmed by RT-qPCR. The mRNA expression levels of seven genes, including Spot14, were altered by >2-fold in AIS patients. Spot14/S14R was selected for further investigation. The results of the western blotting demonstrated that mRNA and protein expression levels of Spot14/S14R were significantly higher in AIS patients than the controls (P<0.05). Immunohistochemistry demonstrated Spot14 was expressed in 85% (17/20 cases) in adipose tissue samples from AIS patients and 23.1% (3/13 cases) of adipose tissue samples from controls. The positive ratio of Spot14 in adipose tissue samples from AIS was significantly higher than the controls (P<0.001). The results of the present study indicated that Spot14/S14R were differently expressed in MSC adipogenesis in AIS patients, and they may be important in the abnormal adipogenic differentiation in AIS. PMID:27082501

  19. Mesenchymal stem cells directly interact with breast cancer cells and promote tumor cell growth in vitro and in vivo.

    Science.gov (United States)

    Mandel, Katharina; Yang, Yuanyuan; Schambach, Axel; Glage, Silke; Otte, Anna; Hass, Ralf

    2013-12-01

    Cellular interactions were investigated between human mesenchymal stem cells (MSC) and human breast cancer cells. Co-culture of the two cell populations was associated with an MSC-mediated growth stimulation of MDA-MB-231 breast cancer cells. A continuous expansion of tumor cell colonies was progressively surrounded by MSC(GFP) displaying elongated cell bodies. Moreover, some MSC(GFP) and MDA-MB-231(cherry) cells spontaneously generated hybrid/chimeric cell populations, demonstrating a dual (green fluorescent protein+cherry) fluorescence. During a co-culture of 5-6 days, MSC also induced expression of the GPI-anchored CD90 molecule in breast cancer cells, which could not be observed in a transwell assay, suggesting the requirement of direct cellular interactions. Indeed, MSC-mediated CD90 induction in the breast cancer cells could be partially blocked by a gap junction inhibitor and by inhibition of the notch signaling pathway, respectively. Similar findings were observed in vivo by which a subcutaneous injection of a co-culture of primary MSC with MDA-MB-231(GFP) cells into NOD/scid mice exhibited an about 10-fold increased tumor size and enhanced metastatic capacity as compared with the MDA-MB-231(GFP) mono-culture. Flow cytometric evaluation of the co-culture tumors revealed more than 90% of breast cancer cells with about 3% of CD90-positive cells, also suggesting an MSC-mediated in vivo induction of CD90 in MDA-MB-231 cells. Furthermore, immunohistochemical analysis demonstrated an elevated neovascularization and viability in the MSC/MDA-MB-231(GFP)-derived tumors. Together, these data suggested an MSC-mediated growth stimulation of breast cancer cells in vitro and in vivo by which the altered MSC morphology and the appearance of hybrid/chimeric cells and breast cancer-expressing CD90(+) cells indicate mutual cellular alterations.

  20. Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion

    Directory of Open Access Journals (Sweden)

    Elke eEggenhofer

    2012-09-01

    Full Text Available Mesenchymal stem cells (MSC are under investigation as a therapy for a variety of disorders. Although animal models show long term regenerative and immunomodulatory effects of MSC, the fate of MSC after infusion remains to be elucidated. In the present study the localization and viability of MSC was examined by isolation and re-culture of intravenously infused MSC. C57BL/6 MSC (500,000 constitutively expressing DsRed-fluorescent protein and radioactively labeled with Cr-51 were infused via the tail vein in wild type C57BL/6 mice. After 5min, 1h, 24h or 72h, mice were sacrificed and blood, lungs, liver, spleen, kidneys and bone marrow removed. One hour after MSC infusion the majority of Cr-51 was found in the lungs, whereas after 24h Cr-51 was mainly found in the liver. Tissue cultures demonstrated that viable donor MSC were present in the lungs up to 24h after infusion, after which they disappeared. No viable MSC were found in the other organs examined at any time. The induction of ischemia-reperfusion injury in the liver did not trigger the migration of viable MSC to the liver. These results demonstrate that MSC are short-lived after i.v. infusion and that viable MSC do not pass the lungs. Cell debris may be transported to the liver. Long term immunomodulatory and regenerative effects of infused MSC must therefore be mediated via other cell types.

  1. MSc Dissertation

    DEFF Research Database (Denmark)

    Roued-Cunliffe, Henriette

    2008-01-01

    Heritage Portals are in this dissertation defined as deep portals which can give access to external resource contents. This dissertation has developed such a portal which accesses the Swedish SMR, FMIS and the ARK system developed by L – P : Archaeology through web services. The development...... of the web Service for the ARK system was done as a part of this project combined with the creating of a WFS web-mapping service serving the spatial part of the dataset collected as a part of the Sintana project. The textual part of this dataset has been incorporated into an ARK system in the same way...... that the Portus project dataset was. Both these projects are available through the ARK web service. The portal accessed the FMIS and ARK web service and re-maps the XML output to Midas standard formatted XML and combined them. This allows the portal to do a cross-search of the two datasets and return the data...

  2. The Application of MSC Pool Technology in Soft Switch Equipment Disaster Recovery%MSC Pool技术在软交换设备容灾中的应用

    Institute of Scientific and Technical Information of China (English)

    刘扬

    2008-01-01

    重点对MSC Pool技术进行了介绍,并对该技术应用在软交换设备容灾时的优势和可能出现的问题进行了分析,提出了在现网中软交换设备采用MSC Pool组网问题的解决思路并对MSC Pool方式组网建设的应用前景进行了展望.

  3. The Marine Stewardship Council (MSC) and the Making of a Market for ‘Sustainable Fish’

    DEFF Research Database (Denmark)

    Ponte, Stefano

    2012-01-01

    Market-based instruments of fishery governance have been promoted in the past two decades on the basis of two widespread expectations: that complying with sustainability standards will lead to environmental benefits; and that certifications will not discriminate against specific social groups...... the market for ‘sustainable fish’, but success has been accompanied by serious challenges. The MSC has so far failed to convincingly show that its certification system has positive environmental impacts, and it has marginalized Southern fisheries, especially in low-income countries. As an institutional...... solution to the global fishery crisis, the MSC seems to be better tuned to the creation of a market for ‘sustainable fish’ rather than ‘sustainable fisheries’....

  4. The finite element analysis program MSC Marc/Mentat a first introduction

    CERN Document Server

    Öchsner, Andreas

    2016-01-01

    Based on simple examples, this book offers a short introduction to the general-purpose finite element program MSC Marc, a specialized program for non-linear problems (implicit solver) distributed by the MSC Software Corporation, which is commonly used in academia and industry. Today the documentation of all finite element programs includes a variety of step-by-step examples of differing complexity, and in addition, all software companies offer professional workshops on different topics. As such, rather than competing with these, the book focuses on providing simple examples, often single-element problems, which can easily be related to the theory that is discussed in finite element lectures. This makes it an ideal companion book to classical introductory courses on the finite element method.

  5. Aspiration, but not injection, decreases cultured equine mesenchymal stromal cell viability

    OpenAIRE

    Williams, Lynn B.; Russell, Keith A.; Koenig, Judith B.; Thomas G. Koch

    2016-01-01

    Background Recently, equine multipotent mesenchymal stromal cells (MSC) have received significant attention as therapy for various conditions due to their proposed regenerative and immune-modulating capacity. MSC are commonly administered to the patient through a hypodermic needle. Currently, little information is available on the effect of such injection has on equine MSC immediate and delayed viability. We hypothesize that viability of equine MSC is not correlated with needle diameter durin...

  6. Finite element modeling of composite piezoelectric structures with MSC/NASTRAN

    Science.gov (United States)

    Freed, Brian D.; Babuska, Vit

    1997-06-01

    Techniques for modeling structures containing piezoelectric ceramics with MSC/NASTRAN are presented. Unlike other finite element programs such as ANSYS and ABAQUS, MSC/NASTRAN offers no piezoelectric coupled-field elements with which to model smart structures directly. Rather, the analogy between piezoelectric strain and thermally induced strain, which allows temperature change to model piezoelectric voltage actuation, must be used. The application and limitations of this method are discussed. To overcome some of the limitations in modeling piezoelectric effects with the thermal analogy, one and two dimensional finite elements which include piezoelectric coupling were developed and integrated into MSC/NASTRAN as dummy elements. The dummy elements offer an alternative method for modeling piezoelectric structural members. As actuators, the elements support charge and voltage actuation in both static and dynamic analyses. When used as sensors, both strain and strain rate outputs are supported. The elements can be used for modal, transient, and frequency response solutions and facilitate combined thermal and piezoelectric loading.

  7. PDX1- and NGN3-mediated in vitro reprogramming of human bone marrow-derived mesenchymal stromal cells into pancreatic endocrine lineages

    DEFF Research Database (Denmark)

    Limbert, Catarina; Päth, Günter; Ebert, Regina;

    2011-01-01

    Reprogramming of multipotent adult bone marrow (BM)-derived mesenchymal stromal/stem cells (MSC) (BM-MSC) represents one of several strategies for cell-based therapy of diabetes. However, reprogramming primary BM-MSC into pancreatic endocrine lineages has not yet been consistently demonstrated....

  8. 探讨MSC Pool技术在移动软交换网络的研究和应用

    Institute of Scientific and Technical Information of China (English)

    丁中华

    2014-01-01

    MSC Pool技术在移动软交换网络中起到了十分重要的作用,本文对MSC Pool技术的概念和工作原理做了介绍,并分析了MSC Pool技术的要点,以及组建MSC Pool的前提条件。

  9. Immunomodulation by Mesenchymal Stem Cells in Veterinary Species

    OpenAIRE

    Carrade, Danielle D.; Borjesson, Dori L.

    2013-01-01

    Mesenchymal stem cells (MSC) are adult-derived multipotent stem cells that have been derived from almost every tissue. They are classically defined as spindle-shaped, plastic-adherent cells capable of adipogenic, chondrogenic, and osteogenic differentiation. This capacity for trilineage differentiation has been the foundation for research into the use of MSC to regenerate damaged tissues. Recent studies have shown that MSC interact with cells of the immune system and modulate their function. ...

  10. A molecular classification of human mesenchymal stromal cells

    OpenAIRE

    Rohart, Florian; Mason, Elizabeth A.; Matigian, Nicholas; Mosbergen, Rowland; Korn, Othmar; Chen, Tyrone; Butcher, Suzanne; Patel, Jatin; Atkinson, Kerry; Khosrotehrani, Kiarash; Fisk, Nicholas M.; Lê Cao, Kim-Anh; Wells, Christine A

    2016-01-01

    Mesenchymal stromal cells (MSC) are widely used for the study of mesenchymal tissue repair, and increasingly adopted for cell therapy, despite the lack of consensus on the identity of these cells. In part this is due to the lack of specificity of MSC markers. Distinguishing MSC from other stromal cells such as fibroblasts is particularly difficult using standard analysis of surface proteins, and there is an urgent need for improved classification approaches. Transcriptome profiling is commonl...

  11. Allo-reactivity of mesenchymal stem cells in rhesus macaques is dose and haplotype dependent and limits durable cell engraftment in vivo.

    Directory of Open Access Journals (Sweden)

    Iryna A Isakova

    Full Text Available The emerging paradigm that MSCs are immune privileged has fostered the use of "off-the-shelf" allogeneic MSC-based therapies in human clinical trials. However, this approach ignores studies in experimental animals wherein transplantation of MSCs across MHC boundaries elicits measurable allo-immune responses. To determine if MSCs are hypo-immunogeneic, we characterized the immune response in rhesus macaques following intracranial administration of allogeneic vs. autologous MSCs. This analysis revealed unambiguous evidence of productive allo-recognition based on expansion of NK, B and T cell subsets in peripheral blood and detection of allo-specific antibodies in animals administered allogeneic but not autologous MSCs. Moreover, the degree of MHC class I and II mismatch between the MSC donor and recipient significantly influenced the magnitude and nature of the allo-immune response. Consistent with these findings, real-time PCR analysis of brain tissue from female recipients administered varying doses of male, allogeneic MSCs revealed a significant inverse correlation between MSC engraftment levels and cell dose. Changes in post-transplant neutrophil and lymphocyte counts also correlated with dose and were predictive of overall MSC engraftment levels. However, secondary antigen challenge failed to elicit a measurable immune response in allogeneic recipients. Finally, extensive behavior testing of animals revealed no main effect of cell dose on motor skills, social development, or temperament. Collectively, these data indicate that allogeneic MSCs are weakly immunogenic when transplanted across MHC boundaries in rhesus macaques and this negatively impacts durable engraftment levels. Therefore the use of unrelated donor MSCs should be carefully evaluated in human patients.

  12. Application Progress of MSC-stents Complex in Bone Repair%间充质干细胞-支架复合体运用于骨修复的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘印

    2013-01-01

    Bone defect is a common complication after fracture, and how to effectively repair it is the hot topic in the current medical study. The clinical application of bone tissue engineering technology is gradually rising,and MSC-stents complex can effectively combine their advantages,which is beneficial to the treatment of bone defect. Here is to summarize the MSC-stents requirements, such as cell number, microenvironment simulation and related growth factor function etc. ,to provide a reference basis for further studies.%骨缺损是骨折后的常见并发症,如何有效地进行骨修复是当前医学研究的热点.骨组织工程技术在临床上应用逐渐兴起,间充质干细胞(MSC)-支架复合体可有效结合干细胞与支架的骨修复优势,利于骨缺损的治疗.该文总结分析有关MSC-支架复合体条件需求,如细胞数量,微环境模拟,相关生长因子作用等,为今后的深入研究提供参考.

  13. Research on MSC Pool Tecnology and the Solution of Called Recovery for Huawei Enterprise%MSC Pool技术与华为被叫恢复方案

    Institute of Scientific and Technical Information of China (English)

    马欢

    2010-01-01

    MSC Pool是3G核心网建设中最受关注的技术之一,其理论优势在移动现网中有充分表现.使用该技术可满足网络容灾的需要,解决移动网络中的"潮汐效应",减少局间切换及局问位置更新.华为被叫快速恢复方案采用SCCP信令点负荷分担方式实现对PRN信令的备份处理,可用于解决MSC容灾故障.

  14. Mesenchymal stromal cells protect against caspase 3-mediated apoptosis of CD19(+) peripheral B cells through contact-dependent upregulation of VEGF.

    Science.gov (United States)

    Healy, Marc E; Bergin, Ronan; Mahon, Bernard P; English, Karen

    2015-10-15

    The immune suppressive and anti-inflammatory capabilities of bone marrow-derived mesenchymal stromal cells (MSCs) represent an innovative new tool in regenerative medicine and immune regulation. The potent immune suppressive ability of MSC over T cells, dendritic cells, and natural killer cells has been extensively characterized, however, the effect of MSC on B cell function has not yet been clarified. In this study, the direct effect of MSC on peripheral blood B cell function is defined and the mechanism utilized by MSC in enhancing B cell survival in vitro identified. Human MSC supported the activation, proliferation, and survival of purified CD19(+) B cells through a cell contact-dependent mechanism. These effects were not mediated through B cell activating factor or notch signaling. However, cell contact between MSC and B cells resulted in increased production of vascular endothelial growth factor (VEGF) by MSC facilitating AKT phosphorylation within the B cell and inhibiting caspase 3-mediated apoptosis. Blocking studies demonstrated that this cell contact-dependent effect was not dependent on signaling through CXCR4-CXCL12 or through the epidermal growth factor receptor (EGFR). These results suggest that direct cell contact between MSC and B cells supports B cell viability and function, suggesting that MSC may not represent a suitable therapy for B cell-mediated disease. PMID:26076727

  15. Hypoxic culture conditions for Mesenchymal Stromal/Stem Cells from Wharton's jelly: a critical parameter to consider in a therapeutic context.

    Science.gov (United States)

    Reppel, Loic; Margossian, Talar; Yaghi, Layale; Moreau, Philippe; Mercier, Nathalie; Leger, Leonore; Hupont, Sebastien; Stoltz, Jean-Francois; Bensoussan, Daniele; Huselstein, Celine

    2014-01-01

    Mesenchymal Stromal/Stem Cells from human Wharton's jelly (WJ-MSC) are an abundant and interesting source of stem cells for applications in cell and tissue engineering. Their fetal origin confers specific characteristics compared to Mesenchymal Stromal/Stem Cells isolated from human bone marrow (BM-MSC). The aim of this work was to optimize WJ-MSC culture conditions for their subsequent clinical use. We focused on the influence of oxygen concentration during monolayer expansion on several parameters to characterize MSC. Our work distinguished WJ-MSC from BM-MSC in terms of proliferation, telomerase activity and adipogenic differentiation. We also showed that hypoxia had a beneficial effect on proliferation potential, clonogenic capacity and to a lesser extent, on HLA-G expression of WJ-MSC during their expansion. Moreover, we reported for the first time an increase in chondrogenic differentiation when WJ-MSC were expanded under hypoxia. In an allogeneic therapeutic context, production of clinical batches requires generating high numbers of MSC whilst maintaining the cells' properties. Considering our results, hypoxia will be an important parameter to take into account. In addition, the clinical use of WJ-MSC would provide significant numbers of cells with maintenance of their proliferation and differentiation potential, particularly their chondrogenic potential. Due to their chondrogenic differentiation potential, WJ-MSC promise to be an interesting source of MSC for cell therapy or tissue engineering for cartilage repair and/or regeneration.

  16. Paradigms and pragmatic constructivism

    DEFF Research Database (Denmark)

    Nørreklit, Hanne; Nørreklit, Lennart; Mitchell, Falconer

    2010-01-01

    to the analysis of the comment on their past paper. Findings - In addressing each of the issues in turn the authors clarify their analysis. Originality/value - The paper provides an argument for the development of a paradigm for accounting practice derived from the use of pragmatic constructivism....

  17. Paradigms in object recognition

    International Nuclear Information System (INIS)

    A broad range of approaches has been proposed and applied for the complex and rather difficult task of object recognition that involves the determination of object characteristics and object classification into one of many a priori object types. Our paper revises briefly the three main different paradigms in pattern recognition, namely Bayesian statistics, neural networks, and expert systems. (author)

  18. MSC POOL Technology Risk Analysis of Migration Patterns of Different Users%MSC POOL技术中不同用户迁移方式风险分析

    Institute of Scientific and Technical Information of China (English)

    陈巍

    2011-01-01

    该文介绍了MSC POOL的解决方案与技术优势,然后针对MSC POOL中用户迁移的两种方案做了重点阐述,并对不同方案进行风险分析,分析出对不同组网方式下对现网用户的影响.

  19. Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation.

    Science.gov (United States)

    Yang, Zijiang; Concannon, John; Ng, Kelvin S; Seyb, Kathleen; Mortensen, Luke J; Ranganath, Sudhir; Gu, Fangqi; Levy, Oren; Tong, Zhixiang; Martyn, Keir; Zhao, Weian; Lin, Charles P; Glicksman, Marcie A; Karp, Jeffrey M

    2016-07-26

    Pre-treatment or priming of mesenchymal stem cells (MSC) prior to transplantation can significantly augment the immunosuppressive effect of MSC-based therapies. In this study, we screened a library of 1402 FDA-approved bioactive compounds to prime MSC. We identified tetrandrine as a potential hit that activates the secretion of prostaglandin E2 (PGE2), a potent immunosuppressive agent, by MSC. Tetrandrine increased MSC PGE2 secretion through the NF-κB/COX-2 signaling pathway. When co-cultured with mouse macrophages (RAW264.7), tetrandrine-primed MSC attenuated the level of TNF-α secreted by RAW264.7. Furthermore, systemic transplantation of primed MSC into a mouse ear skin inflammation model significantly reduced the level of TNF-α in the inflamed ear, compared to unprimed cells. Screening of small molecules to pre-condition cells prior to transplantation represents a promising strategy to boost the therapeutic potential of cell therapy.

  20. Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion

    NARCIS (Netherlands)

    E. Eggenhofer (Elke); V. Benseler (Volker); H.K. Kroemer (Heyo); F. Popp (Felix); E.K. Geissler (Edward); H.J. Schlitt (Hans); C.C. Baan (Carla); M.H. Dahlke (Marc); M.J. Hoogduijn (Martin)

    2012-01-01

    textabstractMesenchymal stem cells (MSC) are under investigation as a therapy for a variety of disorders. Although animal models show long term regenerative and immunomodulatory effects of MSC, the fate of MSC after infusion remains to be elucidated. In the present study the localization and viabili

  1. The Nature of Paradigms and Paradigm Shifts in Music Education

    Science.gov (United States)

    Panaiotidi, Elvira

    2005-01-01

    In this paper, the author attempts to extend the paradigm approach into the philosophy of music education and to build upon this basis a model for structuring music education discourse. The author begins with an examination of Peter Abbs' account of paradigms and paradigm shifts in arts education. Then she turns to Kuhn's conception and to his…

  2. Research Paradigm of Displaced Aggression

    OpenAIRE

    Tanno, Syota

    2013-01-01

    A review of research paradigm of displaced aggression is presented. The author arranged the Japanese wording of displaced aggression, summarized the historical transition of research on displaced aggression, and reviewed research paradigm of displaced aggression.

  3. Applications of Recombinant DNA Technology in Gastrointestinal Medicine and Hepatology: Basic Paradigms of Molecular Cell Biology. Part C: Protein Synthesis and Post-Translational Processing in Eukaryotic Cells

    Directory of Open Access Journals (Sweden)

    Gary E Wild

    2000-01-01

    Full Text Available The translation of mRNA constitutes the first step in the synthesis of a functional protein. The polypeptide chain is subsequently folded into the appropriate three-dimensional configuration and undergoes a variety of processing steps before being converted into its active form. These processing steps are intimately related to the cellular events that occur in the endoplasmic reticulum and Golgi compartments, and determine the sorting and transport of different proteins to their appropriate destinations within the cell. While the regulation of gene expression occurs primarily at the level of transcription, the expression of many genes can also be controlled at the level of translation. Most proteins can be regulated in response to extracellular signals. In addition, intracellular protein levels can be controlled by differential rates of protein degradation. Thus, the regulation of both the amounts and activities of intracellular proteins ultimately determines all aspects of cell behaviour.

  4. Yoga, Sundhed og Paradigme

    OpenAIRE

    Andersen, Anna Bjerning Berg; Nielsen, Anna Sabine; Zunda, Daniella

    2014-01-01

    Our focal point and core concepts in this paper are science, health and yoga. Our main concern is to shed light on the understanding of these three concepts and how it varies, depending on the scientific approach these concepts are dealt with. The problem statement of this paper is thereby: How is it possible to argue, based on Kuhn's paradigm theory, that yoga/ayurveda and medical science represent fundamentally different views on health, yoga and science? We choose two scientific ap...

  5. Plasmid-based genetic modification of human bone marrow-derived stromal cells: analysis of cell survival and transgene expression after transplantation in rat spinal cord

    Directory of Open Access Journals (Sweden)

    Van Tendeloo Viggo FI

    2007-12-01

    Full Text Available Abstract Background Bone marrow-derived stromal cells (MSC are attractive targets for ex vivo cell and gene therapy. In this context, we investigated the feasibility of a plasmid-based strategy for genetic modification of human (hMSC with enhanced green fluorescent protein (EGFP and neurotrophin (NT3. Three genetically modified hMSC lines (EGFP, NT3, NT3-EGFP were established and used to study cell survival and transgene expression following transplantation in rat spinal cord. Results First, we demonstrate long-term survival of transplanted hMSC-EGFP cells in rat spinal cord under, but not without, appropriate immune suppression. Next, we examined the stability of EGFP or NT3 transgene expression following transplantation of hMSC-EGFP, hMSC-NT3 and hMSC-NT3-EGFP in rat spinal cord. While in vivo EGFP mRNA and protein expression by transplanted hMSC-EGFP cells was readily detectable at different time points post-transplantation, in vivo NT3 mRNA expression by hMSC-NT3 cells and in vivo EGFP protein expression by hMSC-NT3-EGFP cells was, respectively, undetectable or declined rapidly between day 1 and 7 post-transplantation. Further investigation revealed that the observed in vivo decline of EGFP protein expression by hMSC-NT3-EGFP cells: (i was associated with a decrease in transgenic NT3-EGFP mRNA expression as suggested following laser capture micro-dissection analysis of hMSC-NT3-EGFP cell transplants at day 1 and day 7 post-transplantation, (ii did not occur when hMSC-NT3-EGFP cells were transplanted subcutaneously, and (iii was reversed upon re-establishment of hMSC-NT3-EGFP cell cultures at 2 weeks post-transplantation. Finally, because we observed a slowly progressing tumour growth following transplantation of all our hMSC cell transplants, we here demonstrate that omitting immune suppressive therapy is sufficient to prevent further tumour growth and to eradicate malignant xenogeneic cell transplants. Conclusion In this study, we

  6. A Conversation with David Bates, MD, MSc, Chairman of the American Medical Informatics Association

    OpenAIRE

    Raymond, Brian

    2008-01-01

    A world-renowned physician-researcher, David Bates, MD, MSc, is Chief of the Division of General Medicine at the Brigham and Women's Hospital in Boston, MA, and a Professor at Harvard Medical School and the Harvard School of Public Health, where he is codirector of the Program in Clinical Effectiveness. He is the Medical Director of Clinical and Quality Analysis, Information Systems at Partners HealthCare System, Inc. He is also the former Chair of the National Alliance for Primary Care Infor...

  7. DYNAMIC ANALYSIS OF A CRIMPING DEVICE WITH MULTIPLE CAMS USING MSC ADAMS II

    Directory of Open Access Journals (Sweden)

    Gheorghe Popescu

    2012-05-01

    Full Text Available Through the present paper, the author presents the results of the dynamic analysis with MSC ADAMS of the mechanism with a crimping device with 12 tightening cams, designed and used in the technological process of assembly of the indigenous electrical detonators. In this sense, the mechanism with multiple cams is considered a mechanical system and is treated as an assembly of rigid bodies connected by mechanical connections and elastic elements. For shaping and simulation of the mechanism with multiple cams using ADAMS program, the author got through the following stages: construction of the pattern, its testing and simulation, validation, finishing, parametrization, optimization of the pattern.

  8. A Modal Analysis of the Violin Using MSC/NASTRAN and PATRAN

    OpenAIRE

    Knott, George Anthony

    1987-01-01

    The MSC/NASTRAN finite element computer program and a Cray XMP computer were used to study the modal characteristics of a violin with the Stradivari shape . The violin geometry was modeled using an arcs of circles scheme with PATRAN, a finite element graphics pre/postprocessor program. The violin was modeled in-vacu and with free boundry conditions. Belly, back, sound post, bassbar, neck, bridge, tail-piece, strings, rib linings, end and corner blocks are the components of the model. Mode sha...

  9. Umbilical cord fibroblasts: Could they be considered as mesenchymal stem cells?

    Institute of Scientific and Technical Information of China (English)

    Mustapha; Zeddou; Biserka; Relic; Michel; G; Malaise

    2014-01-01

    In cell therapy protocols, many tissues were proposed as a source of mesenchymal stem cells(MSC) isolation. So far, bone marrow(BM) has been presented as the main source of MSC despite the invasive isolation pro-cedure related to this source. During the last years, the umbilical cord(UC) matrix was cited in different studies as a reliable source from which long term ex vivo prolif-erating fibroblasts were isolated but with contradictory data about their immunophenotype, gene expression profile, and differentiation potential. Hence, an inter-esting question emerged: Are cells isolated from cord matrix(UC-MSC) different from other MSCs? In this re-view, we will summarize different studies that isolated and characterized UC-MSC. Considering BM-MSC as gold standard, we will discuss if UC-MSC fulfill different criteria that define MSC, and what remain to be done in this issue.

  10. Novel application of stem cell-derived factors for periodontal regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Inukai, Takeharu, E-mail: t-inukai@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Katagiri, Wataru, E-mail: w-kat@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Yoshimi, Ryoko, E-mail: lianzi@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Osugi, Masashi, E-mail: masashi@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Kawai, Takamasa, E-mail: takamasa@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Hibi, Hideharu, E-mail: hibihi@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan); Ueda, Minoru, E-mail: mueda@med.nagoya-u.ac.jp [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine (Japan)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer Mesenchymal stem cells (MSCs) secrete a variety of cytokines. Black-Right-Pointing-Pointer Cytokines were detected in conditioned medium from cultured MSCs (MSC-CM). Black-Right-Pointing-Pointer MSC-CM enhanced activation of dog MSCs and periodontal ligament cells. Black-Right-Pointing-Pointer MSC-CM significantly promoted alveolar bone and cementum regeneration. Black-Right-Pointing-Pointer Multiple cytokines contained in MSC-CM promote periodontal regeneration. -- Abstract: The effect of conditioned medium from cultured mesenchymal stem cells (MSC-CM) on periodontal regeneration was evaluated. In vitro, MSC-CM stimulated migration and proliferation of dog MSCs (dMSCs) and dog periodontal ligament cells (dPDLCs). Cytokines such as insulin-like growth factor, vascular endothelial growth factor, transforming growth factor-{beta}1, and hepatocyte growth factor were detected in MSC-CM. In vivo, one-wall critical-size, intrabony periodontal defects were surgically created in the mandible of dogs. Dogs with these defects were divided into three groups that received MSC-CM, PBS, or no implants. Absorbable atelo-collagen sponges (TERUPLUG Registered-Sign ) were used as a scaffold material. Based on radiographic and histological observation 4 weeks after transplantation, the defect sites in the MSC-CM group displayed significantly greater alveolar bone and cementum regeneration than the other groups. These findings suggest that MSC-CM enhanced periodontal regeneration due to multiple cytokines contained in MSC-CM.

  11. Novel application of stem cell-derived factors for periodontal regeneration

    International Nuclear Information System (INIS)

    Highlights: ► Mesenchymal stem cells (MSCs) secrete a variety of cytokines. ► Cytokines were detected in conditioned medium from cultured MSCs (MSC-CM). ► MSC-CM enhanced activation of dog MSCs and periodontal ligament cells. ► MSC-CM significantly promoted alveolar bone and cementum regeneration. ► Multiple cytokines contained in MSC-CM promote periodontal regeneration. -- Abstract: The effect of conditioned medium from cultured mesenchymal stem cells (MSC-CM) on periodontal regeneration was evaluated. In vitro, MSC-CM stimulated migration and proliferation of dog MSCs (dMSCs) and dog periodontal ligament cells (dPDLCs). Cytokines such as insulin-like growth factor, vascular endothelial growth factor, transforming growth factor-β1, and hepatocyte growth factor were detected in MSC-CM. In vivo, one-wall critical-size, intrabony periodontal defects were surgically created in the mandible of dogs. Dogs with these defects were divided into three groups that received MSC-CM, PBS, or no implants. Absorbable atelo-collagen sponges (TERUPLUG®) were used as a scaffold material. Based on radiographic and histological observation 4 weeks after transplantation, the defect sites in the MSC-CM group displayed significantly greater alveolar bone and cementum regeneration than the other groups. These findings suggest that MSC-CM enhanced periodontal regeneration due to multiple cytokines contained in MSC-CM.

  12. Parameters in three-dimensional osteospheroids of telomerized human mesenchymal (stromal) stem cells grown on osteoconductive scaffolds that predict in vivo bone-forming potential

    DEFF Research Database (Denmark)

    Burns, Jorge S; Hansen, Pernille Lund; Larsen, Kenneth H;

    2010-01-01

    Osteoblastic differentiation of human mesenchymal stem cells (hMSC) in monolayer culture is artefactual, lacking an organized bone-like matrix. We present a highly reproducible microwell protocol generating three-dimensional ex vivo multicellular aggregates of telomerized hMSC (hMSC-telomerase re...

  13. Impact of bacteria and bacterial components on osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Fiedler, Tomas, E-mail: tomas.fiedler@med.uni-rostock.de [Institute for Medical Microbiology, Virology, and Hygiene, Rostock University Medical Center, Schillingallee 70, D-18057 Rostock (Germany); Salamon, Achim; Adam, Stefanie; Herzmann, Nicole [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Taubenheim, Jan [Institute for Medical Microbiology, Virology, and Hygiene, Rostock University Medical Center, Schillingallee 70, D-18057 Rostock (Germany); Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Peters, Kirsten [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany)

    2013-11-01

    Adult mesenchymal stem cells (MSC) are present in several tissues, e.g. bone marrow, heart muscle, brain and subcutaneous adipose tissue. In invasive infections MSC get in contact with bacteria and bacterial components. Not much is known about how bacterial pathogens interact with MSC and how contact to bacteria influences MSC viability and differentiation potential. In this study we investigated the impact of three different wound infection relevant bacteria, Escherichia coli, Staphylococcus aureus, and Streptococcus pyogenes, and the cell wall components lipopolysaccharide (LPS; Gram-negative bacteria) and lipoteichoic acid (LTA; Gram-positive bacteria) on viability, proliferation, and osteogenic as well as adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (adMSC). We show that all three tested species were able to attach to and internalize into adMSC. The heat-inactivated Gram-negative E. coli as well as LPS were able to induce proliferation and osteogenic differentiation but reduce adipogenic differentiation of adMSC. Conspicuously, the heat-inactivated Gram-positive species showed the same effects on proliferation and adipogenic differentiation, while its cell wall component LTA exhibited no significant impact on adMSC. Therefore, our data demonstrate that osteogenic and adipogenic differentiation of adMSC is influenced in an oppositional fashion by bacterial antigens and that MSC-governed regeneration is not necessarily reduced under infectious conditions. - Highlights: • Staphylococcus aureus, Streptococcus pyogenes and Escherichia coli bind to and internalize into adMSC. • Heat-inactivated cells of these bacterial species trigger proliferation of adMSC. • Heat-inactivated E. coli and LPS induce osteogenic differentiation of adMSC. • Heat-inactivated E. coli and LPS reduce adipogenic differentiation of adMSC. • LTA does not influence adipogenic or osteogenic differentiation of adMSC.

  14. Paradigm, science and society

    Directory of Open Access Journals (Sweden)

    N.T. van der Merwe

    1975-03-01

    Full Text Available The subject of my contribution to the Taljaard Festschrift is focused on a cardinal aspect of the contemporary discussion in the area of theory of science, namely the relationship between science and society', and in this connection especially the role ascribed by certain scholars to paradigms in the practice of science. Because of its bridge function, the first task will be a global getting acquainted with some characteristic accents in contemporary theory of science. If this is successful, it can hopefully open up avenues for a view of the relationship of the remaining two components of the above mentioned subject.

  15. SUSTAINABLE DEVELOPMENT PARADIGM - SYNOPSIS

    Directory of Open Access Journals (Sweden)

    Constantinescu Andreea

    2014-07-01

    Full Text Available Even if sustainable development is a concept that gained quite recently its scientific prestige, through contribution of researchers its content has upgraded to a high degree of conceptual luggage and, through contribution from governance representatives, has gained an impressive good-practice background. Allowing the use of different methodological premises and conceptual tools, sustainable development paradigm is equipped with all the elements that would allow the opening of new horizons of knowledge. Based on the facility which can operate the concept of sustainable development, the European Union aims to develop both a more competitive economy based on environmental protection as well as a new governance of economic policy. This on one hand demonstrates the sustainable development ability to irradiate creativity towards the establishment of interdisciplinary bridges and on the other hand explains the growing interest of researchers interested in the problem of analyzing in detail this fruitful concept. Launched first as a theoretical framework to serve justify actions responsible for weighting economic growth, the concept of Sustainable Development has quickly become a topic of ethical debate circumscribed to the area of perfectibility of human nature to the necessity registry. In this regard, the philosophical content of this paradigm could not remain outside researchers concerns, who want to provide both policy makers and the general public a wide range of evidence to demonstrate the viability of this paradigm. Academia waits until maximization of the contribution of governance to achieve sustainable economic development, which consists in conjunction of this upward path with the momentum given by public policy sync, perfectly adapted for globalization era and all crises to come. However, because this concept based its structure and composition on three pillars, equally important economy, society and environment any attempt to strengthen

  16. Challenging the Innovation Paradigm

    CERN Document Server

    Sveiby, Karl Erik; Segercrantz, Beata

    2012-01-01

    Innovation is almost always seen as a "good thing". Challenging the Innovation Paradigm is a critical analysis of the innovation frenzy and contemporary innovation research. The one-sided focus on desirable effects of innovation misses many opportunities to reduce the undesirable consequences. Authors in this book show how systemic effects outside the innovating firms reduce the net benefits of innovation for individual employees, customers, as well as for society as a whole - also the innovators' own organizations. This book analyzes the dominant discourses that construct and recons

  17. Human Adipose Tissue-Derived Mesenchymal Stem Cells Abrogate Plasmablast Formation and Induce Regulatory B Cells Independently of T Helper Cells

    NARCIS (Netherlands)

    Franquesa, M.; Mensah, F. K.; Huizinga, R.; Strini, T.; Boon, L.; Lombardo, E.; DelaRosa, O.; Laman, J. D.; Grinyo, J. M.; Weimar, W.; Betjes, M. G. H.; Baan, C. C.; Hoogduijn, M. J.

    2015-01-01

    Mesenchymal or stromal stem cells (MSC) interact with cells of the immune system in multiple ways. Modulation of the immune system by MSC is believed to be a therapeutic option for autoimmune disease and transplant rejection. In recent years, B cells have moved into the focus of the attention as tar

  18. Testing the Paracrine Properties of Human Mesenchymal Stem Cells Using Conditioned Medium.

    Science.gov (United States)

    Danieli, Patrizia; Malpasso, Giuseppe; Ciuffreda, Maria Chiara; Gnecchi, Massimiliano

    2016-01-01

    Mesenchymal stem cells (MSC) produce and secrete a great variety of cytokines and chemokines that play beneficial paracrine actions when MSC are used for tissue repair. The conditioned medium (CM) derived from MSC can be used both in vitro and in vivo to test specific paracrine effects or to screen putative paracrine/autocrine mediators by proteomics.In this chapter, we describe a straightforward method to prepare MSC-derived CM. Furthermore, we summarize some in vitro assays useful for testing the cytoprotective, angiogenic, and regenerative activity of CM. These assays are very helpful when studying the role of MSC in cardiac repair and regeneration. PMID:27236688

  19. Placenta Mesenchymal Stem Cell Derived Exosomes Confer Plasticity on Fibroblasts.

    Science.gov (United States)

    Tooi, Masayuki; Komaki, Motohiro; Morioka, Chikako; Honda, Izumi; Iwasaki, Kengo; Yokoyama, Naoki; Ayame, Hirohito; Izumi, Yuichi; Morita, Ikuo

    2016-07-01

    Mesenchymal stem cell (MSC)-conditioned medium (MSC-CM) has been reported to enhance wound healing. Exosomes contain nucleic acids, proteins, and lipids, and function as an intercellular communication vehicle for mediating some paracrine effects. However, the function of MSC-derived exosomes (MSC-exo) remains elusive. In this study, we isolated human placenta MSC (PlaMSC)-derived exosomes (PlaMSC-exo) and examined their function in vitro. PlaMSCs were isolated from human term placenta using enzymatic digestion. PlaMSC-exo were prepared from the conditioned medium of PlaMSC (PlaMSC-CM) by ultracentrifugation. The expression of stemness-related genes, such as OCT4 and NANOG, in normal adult human dermal fibroblasts (NHDF) after incubation with PlaMSC-exo was measured by real-time reverse transcriptase PCR analysis (real-time PCR). The effect of PlaMSC-exo on OCT4 transcription activity was assessed using Oct4-EGFP reporter mice-derived dermal fibroblasts. The stimulating effects of PlaMSC-exo on osteoblastic and adipocyte-differentiation of NHDF were evaluated by alkaline phosphatase (ALP), and Alizarin red S- and oil red O-staining, respectively. The expression of osteoblast- and adipocyte-related genes was also assessed by real-time PCR. The treatment of NHDF with PlaMSC-exo significantly upregulated OCT4 and NANOG mRNA expression. PlaMSC-exo also enhanced OCT4 transcription. The NHDF treated with PlaMSC-exo exhibited osteoblastic and adipocyte-differentiation in osteogenic and adipogenic induction media. PlaMSC-exo increase the expression of OCT4 and NANOG mRNA in fibroblasts. As a result, PlaMSC-exo influence the differentiation competence of fibroblasts to both osteoblastic and adipocyte-differentiation. It shows a new feature of MSCs and the possibility of clinical application of MSC-exo. J. Cell. Biochem. 117: 1658-1670, 2016. © 2015 Wiley Periodicals, Inc. PMID:26640165

  20. Marketing! Where is Paradigm?

    Directory of Open Access Journals (Sweden)

    Deosir Flávio Lobo de Castro Júnior

    2015-09-01

    Full Text Available The quantitative- qualitative debate is not a new discussion. The aim of this study therefore is to check through the concept of paradigm, new perspectives to understand the academic research in marketing, developments of marketing thinking and methodologies used in the studies of quality of service. Without pretending to exhaust the subject and present a final conclusion, studies that point to the need and importance of qualitative research, as it helps the researcher to better understand the complex nature of the social world in which we live are presented. According to Santana and Gomes (2007, after examining the discussion of Hegel and Kant, reason and conclude that epistemology itself are historical buildings and evolve from contradictions. This article is divided into five moments. The first part presents besides introducing the constitution of the goals of this theoretical essay. The second part presents a brief discussion of the concept of paradigm and marketing. The third part presents a historical retrospective of marketing and its evolution from its schools from studies of Miranda and Arruda (2004. The fourth part presents the methodology of the studies on quality of services and finally the fifth part presents the final considerations.

  1. A New Paradigm: Manganese Superoxide Dismutase Influences the Production of H2O2 in Cells and Thereby Their Biological State

    OpenAIRE

    Buettner, Garry R.; Ng, Chin F.; WANG Min; Rodgers, V. G. J.; Schafer, Freya Q.

    2006-01-01

    The principal source of hydrogen peroxide in mitochondria is thought to be from the dismutation of superoxide via the enzyme manganese superoxide dismutase (MnSOD). However, the nature of the effect of SOD on the cellular production of H2O2 is not widely appreciated. The current paradigm is that the presence of SOD results in a lower level of H2O2 because it would prevent the non-enzymatic reactions of superoxide that form H2O2. The goal of this work was to: a) demonstrate that SOD can increa...

  2. Mesenchymal Stem Cell-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Ameliorate Diabetic Polyneuropathy in Mice

    Directory of Open Access Journals (Sweden)

    Tatsuhito Himeno

    2013-01-01

    Full Text Available Background. Although pathological involvements of diabetic polyneuropathy (DPN have been reported, no dependable treatment of DPN has been achieved. Recent studies have shown that mesenchymal stem cells (MSCs ameliorate DPN. Here we demonstrate a differentiation of induced pluripotent stem cells (iPSCs into MSC-like cells and investigate the therapeutic potential of the MSC-like cell transplantation on DPN. Research Design and Methods. For induction into MSC-like cells, GFP-expressing iPSCs were cultured with retinoic acid, followed by adherent culture for 4 months. The MSC-like cells, characterized with flow cytometry and RT-PCR analyses, were transplanted into muscles of streptozotocin-diabetic mice. Three weeks after the transplantation, neurophysiological functions were evaluated. Results. The MSC-like cells expressed MSC markers and angiogenic/neurotrophic factors. The transplanted cells resided in hindlimb muscles and peripheral nerves, and some transplanted cells expressed S100β in the nerves. Impairments of current perception thresholds, nerve conduction velocities, and plantar skin blood flow in the diabetic mice were ameliorated in limbs with the transplanted cells. The capillary number-to-muscle fiber ratios were increased in transplanted hindlimbs of diabetic mice. Conclusions. These results suggest that MSC-like cell transplantation might have therapeutic effects on DPN through secreting angiogenic/neurotrophic factors and differentiation to Schwann cell-like cells.

  3. Instant stem cell therapy: Characterization and concentration of human mesenchymal stem cells in vitro

    OpenAIRE

    Kasten, P; I Beyen; Egermann, M.; AJ Suda; AA Moghaddam; Zimmermann, G; R Luginbühl

    2008-01-01

    In regenerative medicine, there is an approach to avoid expansion of the mesenchymal stem cell (MSC) before implantation. The aim of this study was to compare methods for instant MSC therapy by use of a portable, automatic and closed system centrifuge that allows for the concentration of MSCs. The main outcome measures were the amount of MSCs per millilitre of bone marrow (BM), clusters of differentiation (CD), proliferation and differentiation capacities of the MSC. A volume reduction protoc...

  4. Human mesenchymal stem cells: from basic biology to clinical applications

    DEFF Research Database (Denmark)

    Abdallah, B M; Kassem, M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are bein...

  5. Adult Stromal (Skeletal, Mesenchymal) Stem Cells: Advances Towards Clinical Applications

    DEFF Research Database (Denmark)

    Kermani, Abbas Jafari; Harkness, Linda; Zaher, Walid;

    2014-01-01

    Mesenchymal Stem Cells (MSC) are non-hematopoietic adult stromal cells that reside in a perivascular niche in close association with pericytes and endothelial cells and possess self-renewal and multi-lineage differentiation capacity. The origin, unique properties, and therapeutic benefits of MSC ...

  6. Proteomics reveals multiple routes to the osteogenic phenotype in mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Yener Bülent

    2007-10-01

    Full Text Available Abstract Background Recently, we demonstrated that human mesenchymal stem cells (hMSC stimulated with dexamethazone undergo gene focusing during osteogenic differentiation (Stem Cells Dev 14(6: 1608–20, 2005. Here, we examine the protein expression profiles of three additional populations of hMSC stimulated to undergo osteogenic differentiation via either contact with pro-osteogenic extracellular matrix (ECM proteins (collagen I, vitronectin, or laminin-5 or osteogenic media supplements (OS media. Specifically, we annotate these four protein expression profiles, as well as profiles from naïve hMSC and differentiated human osteoblasts (hOST, with known gene ontologies and analyze them as a tensor with modes for the expressed proteins, gene ontologies, and stimulants. Results Direct component analysis in the gene ontology space identifies three components that account for 90% of the variance between hMSC, osteoblasts, and the four stimulated hMSC populations. The directed component maps the differentiation stages of the stimulated stem cell populations along the differentiation axis created by the difference in the expression profiles of hMSC and hOST. Surprisingly, hMSC treated with ECM proteins lie closer to osteoblasts than do hMSC treated with OS media. Additionally, the second component demonstrates that proteomic profiles of collagen I- and vitronectin-stimulated hMSC are distinct from those of OS-stimulated cells. A three-mode tensor analysis reveals additional focus proteins critical for characterizing the phenotypic variations between naïve hMSC, partially differentiated hMSC, and hOST. Conclusion The differences between the proteomic profiles of OS-stimulated hMSC and ECM-hMSC characterize different transitional phenotypes en route to becoming osteoblasts. This conclusion is arrived at via a three-mode tensor analysis validated using hMSC plated on laminin-5.

  7. The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels.

    Science.gov (United States)

    Bavi, Navid; Cortes, D Marien; Cox, Charles D; Rohde, Paul R; Liu, Weihong; Deitmer, Joachim W; Bavi, Omid; Strop, Pavel; Hill, Adam P; Rees, Douglas; Corry, Ben; Perozo, Eduardo; Martinac, Boris

    2016-01-01

    The bacterial mechanosensitive channel MscL gates in response to membrane tension as a result of mechanical force transmitted directly to the channel from the lipid bilayer. MscL represents an excellent model system to study the basic biophysical principles of mechanosensory transduction. However, understanding of the essential structural components that transduce bilayer tension into channel gating remains incomplete. Here using multiple experimental and computational approaches, we demonstrate that the amphipathic N-terminal helix of MscL acts as a crucial structural element during tension-induced gating, both stabilizing the closed state and coupling the channel to the membrane. We propose that this may also represent a common principle in the gating cycle of unrelated mechanosensitive ion channels, allowing the coupling of channel conformation to membrane dynamics. PMID:27329693

  8. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Demuth, Christina; Safwat, Akmal;

    2016-01-01

    growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8......) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI....... However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin....

  9. Structural investigation of MscL gating using experimental data and coarse grained MD simulations.

    Directory of Open Access Journals (Sweden)

    Evelyne Deplazes

    Full Text Available The mechanosensitive channel of large conductance (MscL has become a model system in which to understand mechanosensation, a process involved in osmoregulation and many other physiological functions. While a high resolution closed state structure is available, details of the open structure and the gating mechanism remain unknown. In this study we combine coarse grained simulations with restraints from EPR and FRET experiments to study the structural changes involved in gating with much greater level of conformational sampling than has previously been possible. We generated a set of plausible open pore structures that agree well with existing open pore structures and gating models. Most interestingly, we found that membrane thinning induces a kink in the upper part of TM1 that causes an outward motion of the periplasmic loop away from the pore centre. This previously unobserved structural change might present a new mechanism of tension sensing and might be related to a functional role in osmoregulation.

  10. The Peter Pan paradigm

    Directory of Open Access Journals (Sweden)

    Larson Janet E

    2008-01-01

    Full Text Available Abstract Genetic and environmental agents that disrupt organogenesis are numerous and well described. Less well established, however, is the role of delay in the developmental processes that yield functionally immature tissues at birth. Evidence is mounting that organs do not continue to develop postnatally in the context of these organogenesis insults, condemning the patient to utilize under-developed tissues for adult processes. These poorly differentiated organs may appear histologically normal at birth but with age may deteriorate revealing progressive or adult-onset pathology. The genetic and molecular underpinning of the proposed paradigm reveals the need for a comprehensive systems biology approach to evaluate the role of maternal-fetal environment on organogenesis. You may delay, but time will not Benjamin Franklin USA Founding Father

  11. Canine and Equine Mesenchymal Stem Cells Grown in Serum Free Media Have Altered Immunophenotype

    OpenAIRE

    Clark, Kaitlin C.; Kol, Amir; Shahbenderian, Salpi; Granick, Jennifer L.; Walker, Naomi J.; Borjesson, Dori L.

    2015-01-01

    Mesenchymal stem cell (MSC) therapy is being increasingly used to treat dogs and horses with naturally-occurring diseases. However these animals also serve as critical large animal models for ongoing translation of cell therapy products to the human market. MSC manufacture for clinical use mandates improvement in cell culture systems to meet demands for higher MSC numbers and removal of xeno-proteins (i.e. fetal bovine serum, FBS). While serum-free media (SFM) is commercially available, its a...

  12. Paradigms for parasite conservation.

    Science.gov (United States)

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  13. Paradigms for parasite conservation.

    Science.gov (United States)

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  14. Differentiation of Bone Marrow: Derived Mesenchymal Stem Cells into Hepatocyte-like Cells.

    Science.gov (United States)

    Al Ghrbawy, Nesrien M; Afify, Reham Abdel Aleem Mohamed; Dyaa, Nehal; El Sayed, Asmaa A

    2016-09-01

    Cirrhosis is the end-stage liver fibrosis, whereby normal liver architecture is disrupted by fibrotic bands, parenchymal nodules and vascular distortion. Portal hypertension and hepatocyte dysfunction are the end results and give rise to major systemic complications and premature death. Mesenchymal stem cells (MSC) have the capacity of self-renew and to give rise to cells of various lineages, so MSC can be isolated from bone marrow (BM) and induced to differentiate into hepatocyte-like cells. MSC were induced to differentiate into hepatocyte-like cells by hepatotic growth factor (HGF) and fibroblast growth factor-4 (FGF-4). Differentiated cells were examined for the expression of hepatocyte-specific markers and hepatocyte functions. MSC were isolated. Flow cytometry analysis showed that they expressed the MSC-specific markers, reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that MSC expressed the hepatocyte-specific marker cytokeratin 18 (CK-18) following hepatocyte induction. This study demonstrates that BM-derived-MSC can differentiate into functional hepatocyte-like cells following the induction of HGF and FGF-4. MSC can serve as a favorable cell source for tissue engineering in the treatment of liver disease. PMID:27429519

  15. Induction of miR-146a by multiple myeloma cells in mesenchymal stromal cells stimulates their pro-tumoral activity.

    Science.gov (United States)

    De Veirman, Kim; Wang, Jinheng; Xu, Song; Leleu, Xavier; Himpe, Eddy; Maes, Ken; De Bruyne, Elke; Van Valckenborgh, Els; Vanderkerken, Karin; Menu, Eline; Van Riet, Ivan

    2016-07-10

    Mutual communication between multiple myeloma (MM) cells and mesenchymal stromal cells (MSC) plays a pivotal role in supporting MM progression. In MM, MSC exhibit a different genomic profile and dysregulated cytokine secretion compared to normal MSC, however the mechanisms involved in these changes are not fully understood. Here, we examined the miRNA changes in human MSC after culture with conditioned medium of MM cells and found 19 dysregulated miRNAs, including upregulated miR-146a. Moreover, exosomes derived from MM cells contained miR-146a and could be transferred into MSC. After overexpressing miR-146a in MSC, secretion of several cytokines and chemokines including CXCL1, IL6, IL-8, IP-10, MCP-1, and CCL-5 was elevated, resulting in the enhancement of MM cell viability and migration. DAPT, an inhibitor of the endogenous Notch pathway, was able to abrogate the miR-146a-induced increase of cytokines in MSC, suggesting the involvement of the Notch pathway. Taken together, our results demonstrate a positive feedback loop between MM cells and MSC: MM cells promote the increase of miR146a in MSC which leads to more cytokine secretion, which in turn favors MM cell growth and migration. PMID:27102001

  16. Cause of Errors Associated with Application of Drucker-Prager Yield Criterion in MSC/NASTRAN Program%MSC/NASTRAN程序中Drucker-Prager屈服准则引起误差的原因探讨

    Institute of Scientific and Technical Information of China (English)

    王进军

    2000-01-01

    When the Drucker-Prager yield criterion is used, the MSC/NASTRAN program frequently predicts noticeable errors. The relevant part of NASTRAN Handbook was checked and some errors in the elasto-plastics theory used in NASTRAN were detected in this paper. The procurement to prove these errors was verified by numerical calculation.

  17. Prenatal transplantation of mesenchymal stem cells to treat osteogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Jerry KY Chan

    2014-10-01

    Full Text Available Osteogenesis Imperfecta (OI can be a severe disorder that can be diagnosed before birth. Transplantation of mesenchymal stem cells (MSC has the potential to improve the bone structure, growth and fracture healing. In this review we give an introduction to OI and MSC, and the basis for prenatal and postnatal transplantation in OI. We also summarize the two patients with OI who has received prenatal and postnatal transplantation of MSC.The findings suggest that prenatal transplantation of allogeneic MSC in OI is safe. The cell therapy is of likely clinical benefit with improved linear growth, mobility and reduced fracture incidence. Unfortunately, the effect is transient. For this reason postnatal booster infusions using same-donor MSC have been performed with clinical benefit, and without any adverse events.So far there is limited experience in this specific field and proper studies are required to accurately conclude on clinical benefits of MSC transplantation to treat OI.

  18. Naturalistic Inquiry: Paradigm and Method.

    Science.gov (United States)

    Lotto, Linda S.

    Despite the rhetoric acclaiming it as a new paradigm, educational researchers have tended to treat naturalistic inquiry as a new or alternative method employed within the dominant, rationalistic paradigm. Spokespersons for naturalistic inquiry tend to concentrate on what one does differently rather than how one perceives what one is doing…

  19. Reduced reactivation from dormancy but maintained lineage choice of human mesenchymal stem cells with donor age.

    Directory of Open Access Journals (Sweden)

    Verena Dexheimer

    Full Text Available UNLABELLED: Mesenchymal stem cells (MSC are promising for cell-based regeneration therapies but up to date it is still controversial whether their function is maintained throughout ageing. Aim of this study was to address whether frequency, activation in vitro, replicative function, and in vitro lineage choice of MSC is maintained throughout ageing to answer the question whether MSC-based regeneration strategies should be restricted to younger individuals. MSC from bone marrow aspirates of 28 donors (5-80 years were characterized regarding colony-forming unit-fibroblast (CFU-F numbers, single cell cloning efficiency (SSCE, osteogenic, adipogenic and chondrogenic differentiation capacity in vitro. Alkaline phosphatase (ALP activity, mineralization, Oil Red O content, proteoglycan- and collagen type II deposition were quantified. While CFU-F frequency was maintained, SSCE and early proliferation rate decreased significantly with advanced donor age. MSC with higher proliferation rate before start of induction showed stronger osteogenic, adipogenic and chondrogenic differentiation. MSC with high osteogenic capacity underwent better chondrogenesis and showed a trend to better adipogenesis. Lineage choice was, however, unaltered with age. CONCLUSION: Ageing influenced activation from dormancy and replicative function of MSC in a way that it may be more demanding to mobilize MSC to fast cell growth at advanced age. Since fast proliferation came along with high multilineage capacity, the proliferation status of expanded MSC rather than donor age may provide an argument to restrict MSC-based therapies to certain individuals.

  20. Stem cell technology for bone regeneration: current status and potential applications

    Directory of Open Access Journals (Sweden)

    Asatrian G

    2015-02-01

    Full Text Available Greg Asatrian,1 Dalton Pham,1,2 Winters R Hardy,3 Aaron W James,1–3 Bruno Peault3,4 1Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, 2Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, 3UCLA/Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, CA, USA; 4Medical Research Council Centre for Regenerative Medicine, Edinburgh, Scotland, UK Abstract: Continued improvements in the understanding and application of mesenchymal stem cells (MSC have revolutionized tissue engineering. This is particularly true within the field of skeletal regenerative medicine. However, much remains unknown regarding the native origins of MSC, the relative advantages of different MSC populations for bone regeneration, and even the biologic safety of such unpurified, grossly characterized cells. This review will first summarize the initial discovery of MSC, as well as the current and future applications of MSC in bone tissue engineering. Next, the relative advantages and disadvantages of MSC isolated from distinct tissue origins are debated, including the MSC from adipose, bone marrow, and dental pulp, among others. The perivascular origin of MSC is next discussed. Finally, we briefly comment on pluripotent stem cell populations and their possible application in bone tissue engineering. While continually expanding, the field of MSC-based bone tissue engineering and regeneration shows potential to become a clinical reality in the not-so-distant future.Keywords: mesenchymal stem cell, pericyte, bone tissue engineering, MSC, ASC, DMSC

  1. [Exosomes Derived from Mesenchymal Stem Cells--the Future Ideal Vector of Biological Therapy].

    Science.gov (United States)

    Zhang, Juan; Shi, Jing-Shu; Li, Jian

    2015-08-01

    MSC-exosomes are homogeneous menbrane vesicles with diameter 40-100 nm, derived from mesenchymal stem cells at physiological or pathology conditions. MSC-exosomes contain a great quantity and a wide variety of bioactive substances, such as proteins and miRNA. MSC-exosomes transfer bioactive substances to recipient cells to affect their functions through membrane fusion or endocytosis, which like the storage pools of signal vehicles for cell-to-cell comunication in vivo. MSC-exosomes can mimic the beneficial effect of MSC treatment, such as the promotion of tissue repair or the immune regulation. The biological property and functions of MSC-exosomes are reviwed in this article. PMID:26314469

  2. Mesenchymal stem cell-conditioned medium prevents radiation-induced liver injury by inhibiting inflammation and protecting sinusoidal endothelial cells

    International Nuclear Information System (INIS)

    Current management of radiation-induced liver injury is limited. Sinusoidal endothelial cell (SEC) apoptosis and inflammation are considered to be initiating events in hepatic damage. We hypothesized that mesenchymal stem cells (MSCs) possess anti-apoptotic and anti-inflammatory actions during hepatic irradiation, acting via paracrine mechanisms. This study aims to examine whether MSC-derived bioactive components are protective against radiation-induced liver injury in rats. MSC-conditioned medium (MSC-CM) was generated from rat bone marrow–derived MSCs. The effect of MSC-CM on the viability of irradiated SECs was examined by flow cytometric analysis. Activation of the Akt and ERK pathways was analyzed by western blot. MSC-CM was also delivered to Sprague–Dawley rats immediately before receiving liver irradiation, followed by testing for pathological features, changes in serum hyaluronic acid, ALT, and inflammatory cytokine levels, and liver cell apoptosis. MSC-CM enhanced the viability of irradiated SECs in vitro and induced Akt and ERK phosphorylation in these cells. Infusion of MSC-CM immediately before liver irradiation provided a significant anti-apoptotic effect on SECs and improved the histopathological features of injury in the irradiated liver. MSC-CM also reduced the secretion and expression of inflammatory cytokines and increased the expression of anti-inflammatory cytokines. MSC-derived bioactive components could be a novel therapeutic approach for treating radiation-induced liver injury. (author)

  3. Capacity Building in IWRM: The IWRM MSc Curriculum at the Water and Environment Centre, Republic of Yemen

    NARCIS (Netherlands)

    Soppe, R.W.O.; Babaqi, A.S.; Huibers, F.P.

    2005-01-01

    Integrated Water Resources Management (IWRM) is an interdisciplinary approach to water resources management, as opposed to water resources development. In developing an MSc curriculum at the Water and Environment Centre (WEC) at Sana'a University in the republic of Yemen, three goals were defined. T

  4. On the structure of the N-terminal domain of the MscL channel: helical bundle or membrane interface.

    Science.gov (United States)

    Iscla, Irene; Wray, Robin; Blount, Paul

    2008-09-01

    The mechanosensitive channel of large conductance, MscL, serves as a biological emergency release valve protecting bacteria from acute osmotic downshock and is to date the best characterized mechanosensitive channel. A well-recognized and supported model for Escherichia coli MscL gating proposes that the N-terminal 11 amino acids of this protein form a bundle of amphipathic helices in the closed state that functionally serves as a cytoplasmic second gate. However, a recently reexamined crystal structure of a closed state of the Mycobacterium tuberculosis MscL shows these helices running along the cytoplasmic surface of the membrane. Thus, it is unclear if one structural model is correct or if they both reflect valid closed states. Here, we have systematically reevaluated this region utilizing cysteine-scanning, in vivo functional characterization, in vivo SCAM, electrophysiological studies, and disulfide-trapping experiments. The disulfide-trapping pattern and functional studies do not support the helical bundle and second-gate hypothesis but correlate well with the proposed structure for M. tuberculosis MscL. We propose a functional model that is consistent with the collective data. PMID:18515388

  5. On the role of individual subunits in MscL gating : "All for one, one for all?"

    NARCIS (Netherlands)

    Mika, Jacek T.; Birkner, Jan P.; Poolman, Bert; Kocer, Armagan

    2013-01-01

    The mechanosensitive channel of large conductance (MscL) is a homopentameric membrane protein that protects bacteria from hypoosmotic stress. Its mechanics are coupled to structural changes in the membrane, yet the molecular mechanism of the transition from closed to open states and the cooperation

  6. Läätsa Kalatööstus järjekordne MSC sertifikaadi omanik / Alar Mik

    Index Scriptorium Estoniae

    Mik, Alar

    2014-01-01

    MSC (Marine Stewardship Council)-märgis toodetel tõendab, et tegemist on keskkonnaalaselt vastutustundliku ettevõttega, kelle toodangutsükkel on kala püüdmisest kuni valmistoodangu tarbijani jõudmiseni rangelt seaduslik ja keskkonnasäästlik. Vestlusest ettevõtte juhatuse liikme Toomas Auliga

  7. M.Sc. in Civil and Structural Engineering:3rd Semester and Master’s Thesis Ideas 2014

    OpenAIRE

    2014-01-01

    The following pages contain a list of project ideas proposed by the scientific staff at the Department of Civil Engineering, Aalborg University, and a number of companies. Most of the project ideas in this catalogue may form the basis for long and short master projects as well as regular 3rd semester projects at the M.Sc. programme in Civil and Structural Engineering.

  8. M.Sc. in Civil and Structural Engineering:3rd Semester and Master’s Thesis Ideas 2011

    OpenAIRE

    2011-01-01

    This catalogue contains a list of project ideas proposed by the scientific staff at the Department of Civil Engineering, Aalborg University, and a number of companies. Most of the project ideas in this catalogue may form the basis for long and short candidate projects as well as regular 3rd semester projects at the M.Sc. programme in Civil and Structural Engineering.

  9. Adipose-derived mesenchymal stem cells from the sand rat: transforming growth factor beta and 3D co-culture with human disc cells stimulate proteoglycan and collagen type I rich extracellular matrix

    OpenAIRE

    Tapp, Hazel; Deepe, Ray; Ingram, Jane A; Kuremsky, Marshall; Hanley, Edward N; Gruber, Helen E.

    2008-01-01

    Introduction Adult mesenchymal stem cell therapy has a potential application in the biological treatment of disc degeneration. Our objectives were: to direct adipose-derived mesenchymal stem cells (AD-MSC) from the sand rat to produce a proteoglycan and collagen type I extracellular matrix (ECM) rich in known ECM components of the annulus fibrosis of disc; and to stimulate proteoglycan production by co-culture of human annulus cells with AD-MSC. Methods AD-MSC were isolated and characterised ...

  10. Molecular characterisation of stromal populations derived from human embryonic stem cells: Similarities to immortalised bone marrow derived stromal stem cells

    Directory of Open Access Journals (Sweden)

    Linda Harkness

    2015-12-01

    Full Text Available Human bone marrow-derived stromal (skeletal stem cells (BM-hMSC are being employed in an increasing number of clinical trials for tissue regeneration. A limiting factor for their clinical use is the inability to obtain sufficient cell numbers. Human embryonic stem cells (hESC can provide an unlimited source of clinical grade cells for therapy. We have generated MSC-like cells from hESC (called here hESC-stromal that exhibit surface markers and differentiate to osteoblasts and adipocytes, similar to BM-hMSC. In the present study, we used microarray analysis to compare the molecular phenotype of hESC-stromal and immortalised BM-hMSC cells (hMSC-TERT. Of the 7379 genes expressed above baseline, only 9.3% of genes were differentially expressed between undifferentiated hESC-stromal and BM-hMSC. Following ex vivo osteoblast induction, 665 and 695 genes exhibited ≥2-fold change (FC in hESC-stromal and BM-hMSC, respectively with 172 genes common to both cell types. Functional annotation of significantly changing genes revealed similarities in gene ontology between the two cell types. Interestingly, genes in categories of cell adhesion/motility and epithelial–mesenchymal transition (EMT were highly enriched in hESC-stromal whereas genes associated with cell cycle processes were enriched in hMSC-TERT. This data suggests that while hESC-stromal cells exhibit a similar molecular phenotype to hMSC-TERT, differences exist that can be explained by ontological differences between these two cell types. hESC-stromal cells can thus be considered as a possible alternative candidate cells for hMSC, to be employed in regenerative medicine protocols.

  11. Maintenance of differentiation potential of human bone marrow mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene despite of extensive proliferation

    International Nuclear Information System (INIS)

    Human bone marrow mesenchymal stem cells (hMSC) represent a population of stem cells that are capable of differentiation into multiple lineages. However, these cells exhibit senescence-associated growth arrest and phenotypic changes during long-term in vitro culture. We have recently demonstrated that overexpression of human telomerase reverse transcriptase (hTERT) in hMSC reconstitutes telomerase activity and extends life span of the cells [Nat. Biotechnol. 20 (2002) 592]. In the present study, we have performed extensive characterization of three independent cell lines derived from the parental hMSC-TERT cell line based on different plating densities during expansion in culture: 1:2 (hMSC-TERT2), 1:4 (hMSC-TERT4), and 1:20 (hMSC-TERT20). The 3 cell lines exhibited differences in morphology and growth rates but they all maintained the characteristics of self-renewing stem cells and the ability to differentiate into multiple mesoderm-type cell lineages: osteoblasts, adipocytes, chondrocytes, and endothelial-like cells over a 3-year period in culture. Also, surface marker studies using flow cytometry showed a pattern similar to that known from normal hMSC. Thus, telomerization of hMSC by hTERT overexpression maintains the stem cell phenotype of hMSC and it may be a useful tool for obtaining enough number of cells with a stable phenotype for mechanistic studies of cell differentiation and for tissue engineering protocols

  12. Human adipose-tissue derived mesenchymal stem cells induce functional de-novo regulatory T cells with methylated FOXP3 gene DNA

    NARCIS (Netherlands)

    Engela, A. U.; Hoogduijn, M. J.; Boer, K.; Litjens, N. H. R.; Betjes, M. G. H.; Weimar, W.; Baan, C. C.

    2013-01-01

    Due to their immunomodulatory properties, mesenchymal stem cells (MSC) are interesting candidates for cellular therapy for autoimmune disorders, graft-versus-host disease and allograft rejection. MSC inhibit the proliferation of effector T cells and induce T cells with a regulatory phenotype. So far

  13. Enhanced neuro-therapeutic potential of Wharton's Jelly-derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture.

    Science.gov (United States)

    Drela, Katarzyna; Lech, Wioletta; Figiel-Dabrowska, Anna; Zychowicz, Marzena; Mikula, Michał; Sarnowska, Anna; Domanska-Janik, Krystyna

    2016-04-01

    Substantial inconsistencies in mesenchymal stem (stromal) cell (MSC) therapy reported in early translational and clinical studies may indicate need for selection of the proper cell population for any particular therapeutic purpose. In the present study we have examined stromal stem cells derived either from umbilical cord Wharton's Jelly (WJ-MSC) or bone marrow (BM-MSC) of adult, healthy donors. The cells characterized in accordance with the International Society for Cellular Therapy (ISCT) indications as well as other phenotypic and functional parameters have been compared under strictly controlled culture conditions. WJ-MSC, in comparison with BM-MSC, exhibited a higher proliferation rate, a greater expansion capability being additionally stimulated under low-oxygen atmosphere, enhanced neurotrophic factors gene expression and spontaneous tendency toward a neural lineage differentiation commitment confirmed by protein and gene marker induction. Our data suggest that WJ-MSC may represent an example of immature-type "pre-MSC," where a substantial cellular component is embryonic-like, pluripotent derivatives with the default neural-like differentiation. These cells may contribute in different extents to nearly all classical MSC populations adversely correlated with the age of cell donors. Our data suggest that neuro-epithelial markers, like nestin, stage specific embryonic antigens-4 or α-smooth muscle actin expressions, may serve as useful indicators of MSC culture neuro-regeneration-associated potency. PMID:26971678

  14. Delivery of human mesenchymal adipose-derived stem cells restores multiple urological dysfunctions in a rat model mimicking radical prostatectomy damages through tissue-specific paracrine mechanisms.

    Science.gov (United States)

    Yiou, René; Mahrouf-Yorgov, Meriem; Trébeau, Céline; Zanaty, Marc; Lecointe, Cécile; Souktani, Richard; Zadigue, Patricia; Figeac, Florence; Rodriguez, Anne-Marie

    2016-02-01

    Urinary incontinence (UI) and erectile dysfunction (ED) are the most common functional urological disorders and the main sequels of radical prostatectomy (RP) for prostate cancer. Mesenchymal stem cell (MSC) therapy holds promise for repairing tissue damage due to RP. Because animal studies accurately replicating post-RP clinical UI and ED are lacking, little is known about the mechanisms underlying the urological benefits of MSC in this setting. To determine whether and by which mechanisms MSC can repair damages to both striated urethral sphincter (SUS) and penis in the same animal, we delivered human multipotent adipose stem cells, used as MSC model, in an immunocompetent rat model replicating post-RP UI and ED. In this model, we demonstrated by using noninvasive methods in the same animal from day 7 to day 90 post-RP injury that MSC administration into both the SUS and the penis significantly improved urinary continence and erectile function. The regenerative effects of MSC therapy were not due to transdifferentiation and robust engraftment at injection sites. Rather, our results suggest that MSC benefits in both target organs may involve a paracrine process with not only soluble factor release by the MSC but also activation of the recipient's secretome. These two effects of MSC varied across target tissues and damaged-cell types. In conclusion, our work provides new insights into the regenerative properties of MSC and supports the ability of MSC from a single source to repair multiple types of damage, such as those seen after RP, in the same individual.

  15. Mesenchymal Stem Cells from Human Extra Ocular Muscle Harbor Neuroectodermal Differentiation Potential.

    Directory of Open Access Journals (Sweden)

    Darilang Mawrie

    Full Text Available Mesenchymal stem cells (MSC have been proposed as suitable candidates for cell therapy for neurological disorderssince they exhibit good neuronal differentiation capacity. However, for better therapeutic outcomes, it is necessary to isolate MSC from a suitable tissue sourcethat posses high neuronal differentiation. In this context, we isolated MSC from extra ocular muscle (EOM tissue and tested the in vitro neuronal differentiation potential. In the current study, EOM tissue derived MSC were characterized and compared with bone marrow derived MSC. We found that EOM derived MSC proliferated as a monolayer and showed similarities in morphology, growth properties and cell surface marker expression with bone marrow derived MSC and expressed high levels of NES, OCT4, NANOG and SOX2 in its undifferentiated state. They also expressed embryonic cell surface marker SSEA4 and their intracellular mitochondrial distribution pattern was similar to that of multipotent stem cells. Although EOM derived MSC differentiated readily into adipocytes, osteocytes and chondrocytes, they differentiated more efficiently into neuroectodermal cells. The differentiation into neuroectodermal cellswas confirmed by the expression of neuronal markers NGFR and MAP2B. Thus, EOM derived MSC might be good candidates for stem cell based therapies for treating neurodegenerative diseases.

  16. Mesenchymal Stem Cells from Human Extra Ocular Muscle Harbor Neuroectodermal Differentiation Potential

    Science.gov (United States)

    Magdalene, Damaris; Bhattacharyya, Jina; Jaganathan, Bithiah Grace

    2016-01-01

    Mesenchymal stem cells (MSC) have been proposed as suitable candidates for cell therapy for neurological disorderssince they exhibit good neuronal differentiation capacity. However, for better therapeutic outcomes, it is necessary to isolate MSC from a suitable tissue sourcethat posses high neuronal differentiation. In this context, we isolated MSC from extra ocular muscle (EOM) tissue and tested the in vitro neuronal differentiation potential. In the current study, EOM tissue derived MSC were characterized and compared with bone marrow derived MSC. We found that EOM derived MSC proliferated as a monolayer and showed similarities in morphology, growth properties and cell surface marker expression with bone marrow derived MSC and expressed high levels of NES, OCT4, NANOG and SOX2 in its undifferentiated state. They also expressed embryonic cell surface marker SSEA4 and their intracellular mitochondrial distribution pattern was similar to that of multipotent stem cells. Although EOM derived MSC differentiated readily into adipocytes, osteocytes and chondrocytes, they differentiated more efficiently into neuroectodermal cells. The differentiation into neuroectodermal cellswas confirmed by the expression of neuronal markers NGFR and MAP2B. Thus, EOM derived MSC might be good candidates for stem cell based therapies for treating neurodegenerative diseases. PMID:27248788

  17. Endothelial cells influence the osteogenic potential of bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Arvidson Kristina

    2009-11-01

    Full Text Available Abstract Background Improved understanding of the interactions between bone cells and endothelial cells involved in osteogenesis should aid the development of new strategies for bone tissue engineering. The aim of the present study was to determine whether direct communication between bone marrow stromal cells (MSC and human umbilical vein endothelial cells (EC could influence the osteogenic potential of MSC in osteogenic factor-free medium. Methods After adding EC to MSC in a direct-contact system, cell viability and morphology were investigated with the WST assay and immnostaining. The effects on osteogenic differentiation of adding EC to MSC was systematically tested by the using Superarray assay and results were confirmed with real-time PCR. Results Five days after the addition of EC to MSC in a ratio of 1:5 (EC/MSC significant increases in cell proliferation and cellular bridges between the two cell types were detected, as well as increased mRNA expression of alkaline phosphatase (ALP. This effect was greater than that seen with addition of osteogenic factors such as dexamethasone, ascorbic acid and β-glycerophosphate to the culture medium. The expression of transcription factor Runx2 was enhanced in MSC incubated with osteogenic stimulatory medium, but was not influenced by induction with EC. The expression of Collagen type I was not influenced by EC but the cells grown in the osteogenic factor-free medium exhibited higher expression than those cultured with osteogenic stimulatory medium. Conclusion These results show that co-culturing of EC and MSC for 5 days influences osteogenic differentiation of MSC, an effect that might be independent of Runx2, and enhances the production of ALP by MSC.

  18. Long-lasting inhibitory effects of fetal liver mesenchymal stem cells on T-lymphocyte proliferation.

    Directory of Open Access Journals (Sweden)

    Massimo Giuliani

    Full Text Available Human bone marrow mesenchymal stem cells (BM-MSC are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK cells, Dendritic Cells (DC, and T cells. This study compared the use of MSC isolated from bone marrow and fetal liver (FL-MSC to determine which displayed the most efficient immunosuppressive effects on T cell activation. Although both types of MSC exhibit similar phenotype profile, FL-MSC displays a much more extended in vitro life-span and immunomodulatory properties. When co-cultured with CD3/CD28-stimulated T cells, both BM-MSC and FL-MSC affected T cell proliferation by inhibiting their entry into the cell cycle, by inducing the down-regulation of phospho-retinoblastoma (pRb, cyclins A and D1, as well as up-regulating p27(kip1 expression. The T cell inhibition by MSC was not due to the soluble HLA-G5 isoform, but to the surface expression of HLA-G1, as shown by the need of cell-cell contact and by the use of neutralizing anti-HLA-G antibodies. To note, in a HLA-G-mediated fashion, MSC facilitated the expansion of a CD4(low/CD8(low T subset that had decreased secretion of IFN-γ, and an induced secretion of the immunomodulatory cytokine IL-10. Because of their longer lasting in vitro immunosuppressive properties, mainly mediated by HLA-G, and their more efficient induction of IL-10 production and T cell apoptosis, fetal liver MSC could be considered a new tool for MSC therapy to prevent allograft rejection.

  19. Mesenchymal stem cell therapy for heart disease.

    Science.gov (United States)

    Gnecchi, Massimiliano; Danieli, Patrizia; Cervio, Elisabetta

    2012-08-19

    Mesenchymal stem cells (MSC) are adult stem cells with capacity for self-renewal and multi-lineage differentiation. Initially described in the bone marrow, MSC are also present in other organs and tissues. From a therapeutic perspective, because of their easy preparation and immunologic privilege, MSC are emerging as an extremely promising therapeutic agent for tissue regeneration and repair. Studies in animal models of myocardial infarction have demonstrated the ability of transplanted MSC to engraft and differentiate into cardiomyocytes and vascular cells. Most importantly, engrafted MSC secrete a wide array of soluble factors that mediate beneficial paracrine effects and may greatly contribute to cardiac repair. Together, these properties can be harnessed to both prevent and reverse remodeling in the ischemically injured ventricle. In proof-of-concept and phase I clinical trials, MSC therapy improved left ventricular function, induced reverse remodeling, and decreased scar size. In this review we will focus on the current understanding of MSC biology and MSC mechanism of action in cardiac repair. PMID:22521741

  20. Analysis of SMA Hybrid Composite Structures in MSC.Nastran and ABAQUS

    Science.gov (United States)

    Turner, Travis L.; Patel, Hemant D.

    2005-01-01

    A thermoelastic constitutive model for shape memory alloy (SMA) actuators and SMA hybrid composite (SMAHC) structures was recently implemented in the commercial finite element codes MSC.Nastran and ABAQUS. The model may be easily implemented in any code that has the capability for analysis of laminated composite structures with temperature dependent material properties. The model is also relatively easy to use and requires input of only fundamental engineering properties. A brief description of the model is presented, followed by discussion of implementation and usage in the commercial codes. Results are presented from static and dynamic analysis of SMAHC beams of two types; a beam clamped at each end and a cantilever beam. Nonlinear static (post-buckling) and random response analyses are demonstrated for the first specimen. Static deflection (shape) control is demonstrated for the cantilever beam. Approaches for modeling SMAHC material systems with embedded SMA in ribbon and small round wire product forms are demonstrated and compared. The results from the commercial codes are compared to those from a research code as validation of the commercial implementations; excellent correlation is achieved in all cases.

  1. Functional reactive paradigm advantages for Android development

    OpenAIRE

    SUTULA ALEXANDER

    2015-01-01

    This article describes conceptual difference between imperative, reactive paradigms and functional reactive style advantages in Android development. Solutions of imperative paradigm main problems are described.

  2. Mesenchymal Stem Cell-Derived Microvesicles Support Ex Vivo Expansion of Cord Blood-Derived CD34+ Cells

    Directory of Open Access Journals (Sweden)

    Hui Xie

    2016-01-01

    Full Text Available Mesenchymal stem cells (MSCs are known to support the characteristic properties of hematopoietic stem and progenitor cells (HSPCs in the bone marrow hematopoietic microenvironment. MSCs are used in coculture systems as a feeder layer for the ex vivo expansion of umbilical cord blood (CB to increase the relatively low number of HSPCs in CB. Findings increasingly suggest that MSC-derived microvesicles (MSC-MVs play an important role in the biological functions of their parent cells. We speculate that MSC-MVs may recapitulate the hematopoiesis-supporting effects of their parent cells. In the current study, we found MSC-MVs containing microRNAs that are involved in the regulation of hematopoiesis. We also demonstrated that MSC-MVs could improve the expansion of CB-derived mononuclear cells and CD34+ cells and generate a greater number of primitive progenitor cells in vitro. Additionally, when MSC-MVs were added to the CB-MSC coculture system, they could improve the hematopoiesis-supporting effects of MSCs. These findings highlight the role of MSC-MVs in the ex vivo expansion of CB, which may offer a promising therapeutic approach in CB transplantation.

  3. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells

    DEFF Research Database (Denmark)

    Dokkedahl, Karin Stenderup; Justesen, Jeannette; Clausen, Christian;

    2003-01-01

    -gal+) cells and mean telomere length in early-passage cells obtained from young and old donors. However, MSC from old donors exhibited accelerated senescence evidenced by increased number of SA beta-gal+ cells per PD as compared with young (4% per PD vs 0.4% per PD, respectively). MSC from young and old...

  4. Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Fernando Antonio Fierro

    2015-10-01

    Full Text Available Many therapies using mesenchymal stem cells (MSC rely on their ability to produce and release paracrine signals with chemotactic and pro-angiogenic activity. These characteristics, however, are mostly studied under standard in vitro culture conditions. In contrast, various novel cell-based therapies imply pre-seeding MSC into bio-artificial scaffolds. Here we describe human bone marrow-derived MSC seeded in Integra matrices, a common type of scaffold for dermal regeneration (SDR. We show and measured the distribution of MSC within the SDR, where cells clearly establish physical interactions with the scaffold, exhibiting constant metabolic activity for at least 15 days. In the SDR, MSC secrete VEGF and SDF-1 and induce transwell migration of CD34+ hematopoietic/endothelial progenitor cells, which is inhibited in the presence of a CXCR4/SDF-1 antagonist. MSC in SDR respond to hypoxia by altering levels of angiogenic signals such as Angiogenin, Serpin-1, uPA and IL-8. Finally, we show that MSC-containing SDR that have been pre-incubated in hypoxia show higher infiltration of endothelial cells after implantation into immune deficient mice. Our data show that MSC are fully functional ex vivo when implanted into SDR. In addition, our results strongly support the notion of hypoxic pre-conditioning MSC-containing SDR, in order to promote angiogenesis in the wounds.

  5. Mechano-growth factor induces migration of rat mesenchymal stem cells by altering its mechanical properties and activating ERK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jiamin; Wu, Kewen; Lin, Feng; Luo, Qing; Yang, Li; Shi, Yisong [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Song, Guanbin, E-mail: song@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Sung, Kuo-Li Paul [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412 (United States)

    2013-11-08

    Highlights: •MGF induced the migration of rat MSC in a concentration-dependent manner. •MGF enhanced the mechanical properties of rMSC in inducing its migration. •MGF activated the ERK 1/2 signaling pathway of rMSC in inducing its migration. •rMSC mechanics may synergy with ERK 1/2 pathway in MGF-induced rMSC migration. -- Abstract: Mechano-growth factor (MGF) generated by cells in response to mechanical stimulation has been identified as a mechano effector molecule, playing a key role in regulating mesenchymal stem cell (MSC) function, including proliferation and migration. However, the mechanism(s) underlying how MGF-induced MSC migration occurs is still unclear. In the present study, MGF motivated migration of rat MSCs (rMSCs) in a concentration-dependent manner and optimal concentration of MGF at 50 ng/mL (defined as MGF treatment in this paper) was demonstrated. Notably, enhancement of mechanical properties that is pertinent to cell migration, such as cell traction force and cell stiffness were found to respond to MGF treatment. Furthermore, MGF increased phosphorylation of extracellular signal-regulated kinase (ERK), ERK inhibitor (i.e., PD98059) suppressed ERK phosphorylation, and abolished MGF-induced rMSC migration were found, demonstrating that ERK is involved molecule for MGF-induced rMSC migration. These in vitro evidences of MGF-induced rMSC migration and its direct link to altering rMSC mechanics and activating the ERK pathway, uncover the underlying biomechanical and biological mechanisms of MGF-induced rMSC migration, which may help find MGF-based application of MSC in clinical therapeutics.

  6. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Demouth, Christina; Safwat, Akmal;

    2016-01-01

    growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8......) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI....... However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin....

  7. Mesenchymal stem cells attenuate inflammatory processes in the heart and lung via inhibition of TNF signaling.

    Science.gov (United States)

    Martire, Alessandra; Bedada, Fikru B; Uchida, Shizuka; Pöling, Jochen; Krüger, Marcus; Warnecke, Henning; Richter, Manfred; Kubin, Thomas; Herold, Susanne; Braun, Thomas

    2016-09-01

    Mesenchymal stem cells (MSC) have been used to treat different clinical conditions although the mechanisms by which pathogenetic processes are affected are still poorly understood. We have previously analyzed the homing of bone marrow-derived MSC to diseased tissues characterized by a high degree of mononuclear cell infiltration and postulated that MSC might modulate inflammatory responses. Here, we demonstrate that MSC mitigate adverse tissue remodeling, improve organ function, and extend lifespan in a mouse model of inflammatory dilative cardiomyopathy (DCM). Furthermore, MSC attenuate Lipopolysaccharide-induced acute lung injury indicating a general role in the suppression of inflammatory processes. We found that MSC released sTNF-RI, which suppressed activation of the NFκBp65 pathway in cardiomyocytes during DCM in vivo. Substitution of MSC by recombinant soluble TNF-R partially recapitulated the beneficial effects of MSC while knockdown of TNF-R prevented MSC-mediated suppression of the NFκBp65 pathway and improvement of tissue pathology. We conclude that sTNF-RI is a major part of the paracrine machinery by which MSC effect local inflammatory reactions. PMID:27435289

  8. A molecular classification of human mesenchymal stromal cells.

    Science.gov (United States)

    Rohart, Florian; Mason, Elizabeth A; Matigian, Nicholas; Mosbergen, Rowland; Korn, Othmar; Chen, Tyrone; Butcher, Suzanne; Patel, Jatin; Atkinson, Kerry; Khosrotehrani, Kiarash; Fisk, Nicholas M; Lê Cao, Kim-Anh; Wells, Christine A

    2016-01-01

    Mesenchymal stromal cells (MSC) are widely used for the study of mesenchymal tissue repair, and increasingly adopted for cell therapy, despite the lack of consensus on the identity of these cells. In part this is due to the lack of specificity of MSC markers. Distinguishing MSC from other stromal cells such as fibroblasts is particularly difficult using standard analysis of surface proteins, and there is an urgent need for improved classification approaches. Transcriptome profiling is commonly used to describe and compare different cell types; however, efforts to identify specific markers of rare cellular subsets may be confounded by the small sample sizes of most studies. Consequently, it is difficult to derive reproducible, and therefore useful markers. We addressed the question of MSC classification with a large integrative analysis of many public MSC datasets. We derived a sparse classifier (The Rohart MSC test) that accurately distinguished MSC from non-MSC samples with >97% accuracy on an internal training set of 635 samples from 41 studies derived on 10 different microarray platforms. The classifier was validated on an external test set of 1,291 samples from 65 studies derived on 15 different platforms, with >95% accuracy. The genes that contribute to the MSC classifier formed a protein-interaction network that included known MSC markers. Further evidence of the relevance of this new MSC panel came from the high number of Mendelian disorders associated with mutations in more than 65% of the network. These result in mesenchymal defects, particularly impacting on skeletal growth and function. The Rohart MSC test is a simple in silico test that accurately discriminates MSC from fibroblasts, other adult stem/progenitor cell types or differentiated stromal cells. It has been implemented in the www.stemformatics.org resource, to assist researchers wishing to benchmark their own MSC datasets or data from the public domain. The code is available from the CRAN

  9. Interfacing Sca-1pos Mesenchymal Stem Cells with Biocompatible Scaffolds with Different Chemical Composition and Geometry

    Directory of Open Access Journals (Sweden)

    G. Forte

    2009-01-01

    Full Text Available An immortalized murine mesenchymal stem cell line (mTERT-MSC enriched for Linneg/Sca-1pos fraction has been obtained through the transfection of MSC with murine TERT and single-cell isolation. Such cell line maintained the typical MSC self-renewal capacity and continuously expressed MSC phenotype. Moreover, mTERT-MSC retained the functional features of freshly isolated MSC in culture without evidence of senescence or spontaneous differentiation events. Thus, mTERT-MSC have been cultured onto PLA films, 30 and 100 μm PLA microbeads, and onto unpressed and pressed HYAFF-11 scaffolds. While the cells adhered preserving their morphology on PLA films, clusters of mTERT-MSC were detected on PLA beads and unpressed fibrous scaffolds. Finally, mTERT-MSC were not able to colonize the inner layers of pressed HYAFF-11. Nevertheless, such cell line displayed the ability to preserve Sca-1 expression and to retain multilineage potential when appropriately stimulated on all the scaffolds tested.

  10. Articular cartilage-derived cells hold a strong osteogenic differentiation potential in comparison to mesenchymal stem cells in vitro

    International Nuclear Information System (INIS)

    Cartilaginous matrix-degenerative diseases like osteoarthritis (OA) are characterized by gradual cartilage erosion, and also by increased presence of cells with mesenchymal stem cell (MSC) character within the affected tissues. Moreover, primary chondrocytes long since are known to de-differentiate in vitro and to be chondrogenically re-differentiable. Since both findings appear to conflict with each other, we quantitatively assessed the mesenchymal differentiation potential of OA patient cartilage-derived cells (CDC) towards the osteogenic and adipogenic lineage in vitro and compared it to that of MSC isolated from adipose tissue (adMSC) of healthy donors. We analyzed expression of MSC markers CD29, CD44, CD105, and CD166, and, following osteogenic and adipogenic induction in vitro, quantified their expression of osteogenic and adipogenic differentiation markers. Furthermore, CDC phenotype and proliferation were monitored. We found that CDC exhibit an MSC CD marker expression pattern similar to adMSC and a similar increase in proliferation rate during osteogenic differentiation. In contrast, the marked reduction of proliferation observed during adipogenic differentiation of adMSC was absent in CDC. Quantification of differentiation markers revealed a strong osteogenic differentiation potential for CDC, however almost no capacity for adipogenic differentiation. Since in the pathogenesis of OA, cartilage degeneration coincides with high bone turnover rates, the high osteogenic differentiation potential of OA patient-derived CDC may affect clinical therapeutic regimens aiming at autologous cartilage regeneration in these patients. - Highlights: • We analyze the mesenchymal differentiation capacity of cartilage-derived cells (CDC). • CDC express mesenchymal stem cell (MSC) markers CD29, CD44, CD105, and CD166. • CDC and MSC proliferation is reduced in adipogenesis and increased in osteogenesis. • Adipogenic differentiation is virtually absent in CDC, but

  11. Articular cartilage-derived cells hold a strong osteogenic differentiation potential in comparison to mesenchymal stem cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Salamon, Achim, E-mail: achim.salamon@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Jonitz-Heincke, Anika, E-mail: anika.jonitz@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Adam, Stefanie, E-mail: stefanie.adam@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Rychly, Joachim, E-mail: joachim.rychly@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Müller-Hilke, Brigitte, E-mail: brigitte.mueller-hilke@med.uni-rostock.de [Institute of Immunology, Rostock University Medical Center, Schillingallee 68, D-18057 Rostock (Germany); Bader, Rainer, E-mail: rainer.bader@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Lochner, Katrin, E-mail: katrin.lochner@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Peters, Kirsten, E-mail: kirsten.peters@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany)

    2013-11-01

    Cartilaginous matrix-degenerative diseases like osteoarthritis (OA) are characterized by gradual cartilage erosion, and also by increased presence of cells with mesenchymal stem cell (MSC) character within the affected tissues. Moreover, primary chondrocytes long since are known to de-differentiate in vitro and to be chondrogenically re-differentiable. Since both findings appear to conflict with each other, we quantitatively assessed the mesenchymal differentiation potential of OA patient cartilage-derived cells (CDC) towards the osteogenic and adipogenic lineage in vitro and compared it to that of MSC isolated from adipose tissue (adMSC) of healthy donors. We analyzed expression of MSC markers CD29, CD44, CD105, and CD166, and, following osteogenic and adipogenic induction in vitro, quantified their expression of osteogenic and adipogenic differentiation markers. Furthermore, CDC phenotype and proliferation were monitored. We found that CDC exhibit an MSC CD marker expression pattern similar to adMSC and a similar increase in proliferation rate during osteogenic differentiation. In contrast, the marked reduction of proliferation observed during adipogenic differentiation of adMSC was absent in CDC. Quantification of differentiation markers revealed a strong osteogenic differentiation potential for CDC, however almost no capacity for adipogenic differentiation. Since in the pathogenesis of OA, cartilage degeneration coincides with high bone turnover rates, the high osteogenic differentiation potential of OA patient-derived CDC may affect clinical therapeutic regimens aiming at autologous cartilage regeneration in these patients. - Highlights: • We analyze the mesenchymal differentiation capacity of cartilage-derived cells (CDC). • CDC express mesenchymal stem cell (MSC) markers CD29, CD44, CD105, and CD166. • CDC and MSC proliferation is reduced in adipogenesis and increased in osteogenesis. • Adipogenic differentiation is virtually absent in CDC, but

  12. Long-Duration Three-Dimensional Spheroid Culture Promotes Angiogenic Activities of Adipose-Derived Mesenchymal Stem Cells

    OpenAIRE

    Lee, Jun Hee; Han, Yong-Seok; Lee, Sang Hun

    2016-01-01

    Mesenchymal stem cells (MSCs) offer significant therapeutic promise for various regenerative therapies. However, MSC-based therapy for injury exhibits low efficacy due to the pathological environment in target tissues and the differences between in vitro and in vivo conditions. To address this issue, we developed adipose-derived MSC spheroids as a novel delivery method to preserve the stem cell microenvironment. MSC spheroids were generated by suspension culture for 3 days, and their sizes in...

  13. Interleukin-17A-Induced Human Mesenchymal Stem Cells Are Superior Modulators of Immunological Function.

    Science.gov (United States)

    Sivanathan, Kisha Nandini; Rojas-Canales, Darling M; Hope, Christopher M; Krishnan, Ravi; Carroll, Robert P; Gronthos, Stan; Grey, Shane T; Coates, Patrick T

    2015-09-01

    Interferon-γ (IFN-γ)-preactivated mesenchymal stem cells (MSC-γ) are highly immunosuppressive but immunogenic in vivo due to their inherent expression of major histocompatibility (MHC) molecules. Here, we present an improved approach where we modified human bone marrow-derived MSC with interleukin-17A (MSC-17) to enhance T cell immunosuppression but not their immunogenicity. MSC-17, unlike MSC-γ, showed no induction or upregulation of MHC class I, MHC class II, and T cell costimulatory molecule CD40, but maintained normal MSC morphology and phenotypic marker expression. When cocultured with phytohemagglutinin (PHA)-activated human T cells, MSCs-17 were potent suppressors of T cell proliferation. Furthermore, MSC-17 inhibited surface CD25 expression and suppressed the elaboration of Th1 cytokines, IFN-γ, tumor necrosis factor-α (TNF-α), and IL-2 when compared with untreated MSCs (UT-MSCs). T cell suppression by MSC-17 correlated with increased IL-6 but not with indoleamine 2,3-dioxygenase 1, cyclooxygenase 1, and transforming growth factor β-1. MSC-17 but not MSC-γ consistently induced CD4(+) CD25(high) CD127(low) FoxP3(+) regulatory T cells (iTregs) from PHA-activated CD4(+) CD25(-) T cells. MSC-induced iTregs expressed CD39, CD73, CD69, OX40, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), and glucocorticoid-induced TNFR-related protein (GITR). These suppressive MSCs-17 can engender Tregs to potently suppress T cell activation with minimal immunogenicity and thus represent a superior T cell immunomodulator for clinical application. PMID:26037953

  14. Isolation and analysis of SSEA-4 positive cells derived from fetal marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    LIU Daqing; PEI Xuetao; YANG Yinxiang; GAO Yanhong; YUAN Hongfeng; QIN Lipeng; WANG Yunfang; NAN Xue; SHI Shuangshuang; YUE Wen

    2006-01-01

    A big issue in stem cell research is to derive prospective totipotential stem cells. In this study, fMSC-SSEA-4 cells expressing SSEA-4 antigen were isolated from fetal marrow masenchymal stem cells (fMSCs) using immunomagnetic bead sorting technique. The totipotent cells were identified and their biological characteristics were further studied. The expression of Oct-4 and SSEA-4, carcino- genicity, and the ability to differentiation of fMSC- SSEA-4 cells were evaluated to verify the totipotent potential. fMSC-SSEA-4 cells were isolated successfully from fMSCs (2.5% among fMSCs), while no obvious differences were seen in morphology, growth curve, cell cycle and immunophenotype, Oct-4 and SSEA-4 expression between fMSC-SSEA-4 cells and fMSCs. fMSC-SSEA-4 cells showed normal diploid chromosome karyotype and no carcinoma was induced after inoculation into nude mice. fMSC- SSEA-4 cells could be induced to fat cells, osteogenic cells and neuron-like cells in vitro with different induced factors. The results indicated that there may be a few totipotent cells among the fMSCs and it may offer the experimental basis for the further study and application of fMSCs.

  15. The Impact of IBM Cell Technology on the Programming Paradigm in the Context of Computer Systems for Climate and Weather Models

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Shujia; Duffy, Daniel; Clune, Thomas; Suarez, Max; Williams, Samuel; Halem, Milton

    2009-01-10

    The call for ever-increasing model resolutions and physical processes in climate and weather models demands a continual increase in computing power. The IBM Cell processor's order-of-magnitude peak performance increase over conventional processors makes it very attractive to fulfill this requirement. However, the Cell's characteristics, 256KB local memory per SPE and the new low-level communication mechanism, make it very challenging to port an application. As a trial, we selected the solar radiation component of the NASA GEOS-5 climate model, which: (1) is representative of column physics components (half the total computational time), (2) has an extremely high computational intensity: the ratio of computational load to main memory transfers, and (3) exhibits embarrassingly parallel column computations. In this paper, we converted the baseline code (single-precision Fortran) to C and ported it to an IBM BladeCenter QS20. For performance, we manually SIMDize four independent columns and include several unrolling optimizations. Our results show that when compared with the baseline implementation running on one core of Intel's Xeon Woodcrest, Dempsey, and Itanium2, the Cell is approximately 8.8x, 11.6x, and 12.8x faster, respectively. Our preliminary analysis shows that the Cell can also accelerate the dynamics component (~;;25percent total computational time). We believe these dramatic performance improvements make the Cell processor very competitive as an accelerator.

  16. Intranasal administration of human MSC for ischemic brain injury in the mouse: in vitro and in vivo neuroregenerative functions.

    Directory of Open Access Journals (Sweden)

    Vanessa Donega

    Full Text Available Intranasal treatment with C57BL/6 MSCs reduces lesion volume and improves motor and cognitive behavior in the neonatal hypoxic-ischemic (HI mouse model. In this study, we investigated the potential of human MSCs (hMSCs to treat HI brain injury in the neonatal mouse. Assessing the regenerative capacity of hMSCs is crucial for translation of our knowledge to the clinic. We determined the neuroregenerative potential of hMSCs in vitro and in vivo by intranasal administration 10 d post-HI in neonatal mice. HI was induced in P9 mouse pups. 1×10(6 or 2×10(6 hMSCs were administered intranasally 10 d post-HI. Motor behavior and lesion volume were measured 28 d post-HI. The in vitro capacity of hMSCs to induce differentiation of mouse neural stem cell (mNSC was determined using a transwell co-culture differentiation assay. To determine which chemotactic factors may play a role in mediating migration of MSCs to the lesion, we performed a PCR array on 84 chemotactic factors 10 days following sham-operation, and at 10 and 17 days post-HI. Our results show that 2×10(6 hMSCs decrease lesion volume, improve motor behavior, and reduce scar formation and microglia activity. Moreover, we demonstrate that the differentiation assay reflects the neuroregenerative potential of hMSCs in vivo, as hMSCs induce mNSCs to differentiate into neurons in vitro. We also provide evidence that the chemotactic factor CXCL10 may play an important role in hMSC migration to the lesion site. This is suggested by our finding that CXCL10 is significantly upregulated at 10 days following HI, but not at 17 days after HI, a time when MSCs no longer reach the lesion when given intranasally. The results described in this work also tempt us to contemplate hMSCs not only as a potential treatment option for neonatal encephalopathy, but also for a plethora of degenerative and traumatic injuries of the nervous system.

  17. Longitudinal Cell Tracking and Simultaneous Monitoring of Tissue Regeneration after Cell Treatment of Natural Tendon Disease by Low-Field Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Dagmar Berner

    2016-01-01

    Full Text Available Treatment of tendon disease with multipotent mesenchymal stromal cells (MSC is a promising option to improve tissue regeneration. To elucidate the mechanisms by which MSC support regeneration, longitudinal tracking of MSC labelled with superparamagnetic iron oxide (SPIO by magnetic resonance imaging (MRI could provide important insight. Nine equine patients suffering from tendon disease were treated with SPIO-labelled or nonlabelled allogeneic umbilical cord-derived MSC by local injection. Labelling of MSC was confirmed by microscopy and MRI. All animals were subjected to clinical, ultrasonographical, and low-field MRI examinations before and directly after MSC application as well as 2, 4, and 8 weeks after MSC application. Hypointense artefacts with characteristically low signal intensity were identified at the site of injection of SPIO-MSC in T1- and T2∗-weighted gradient echo MRI sequences. They were visible in all 7 cases treated with SPIO-MSC directly after injection, but not in the control cases treated with nonlabelled MSC. Furthermore, hypointense artefacts remained traceable within the damaged tendon tissue during the whole follow-up period in 5 out of 7 cases. Tendon healing could be monitored at the same time. Clinical and ultrasonographical findings as well as T2-weighted MRI series indicated a gradual improvement of tendon function and structure.

  18. Health Inequities: Evaluation of Two Paradigms

    Science.gov (United States)

    Ashcroft, Rachelle

    2010-01-01

    Social work practice in health is shaped by underlying paradigms. To effectively target health inequities, practitioners need to consider appropriate paradigms. In this exploration of how six health paradigms shape theory and practice, the two health paradigms that most attended to health inequalities are social determinants of health and…

  19. Effects of high glucose on mesenchymal stem cell proliferation and differentiation

    DEFF Research Database (Denmark)

    Li, Yu-Ming; Schilling, Tatjana; Benisch, Peggy;

    2007-01-01

    High glucose (HG) concentrations impair cellular functions and induce apoptosis. Exposition of mesenchymal stem cells (MSC) to HG was reported to reduce colony forming activity and induce premature senescence. We characterized the effects of HG on human MSC in vitro using telomerase-immortalized ......High glucose (HG) concentrations impair cellular functions and induce apoptosis. Exposition of mesenchymal stem cells (MSC) to HG was reported to reduce colony forming activity and induce premature senescence. We characterized the effects of HG on human MSC in vitro using telomerase...

  20. Ketangguhan Retak Dinamik Bahan Komposit GFRP Untuk Helmet Industri Disebabkan Beban Impak Menggunakan MSC/NASTRAN For Windows

    OpenAIRE

    Jusnita

    2010-01-01

    This research is to study computer simulation of glass fiber reinforced plastic (GFRP) plate specimen, by finite element method. Its goal is to know the stress intensity factor and compared them with the critical intensity factor (fracture toughanes/obtained using experimental method. The simulation utilized MSC MSN/NASTRAN for Window software and FEMAP sub program with impact load model. To simplify the simulation process, specimens were drawn in half because of its symmetric. Small meshes...

  1. Cardiac migration of endogenous mesenchymal stromal cells in patients with inflammatory cardiomyopathy.

    Science.gov (United States)

    Schmidt-Lucke, Caroline; Escher, Felicitas; Van Linthout, Sophie; Kühl, Uwe; Miteva, Kapka; Ringe, Jochen; Zobel, Thomas; Schultheiss, Heinz-Peter; Tschöpe, Carsten

    2015-01-01

    Introduction. Mesenchymal stromal cells (MSC) have immunomodulatory features. The aim of this study was to investigate the migration and homing potential of endogenous circulating MSC in virus negative inflammatory cardiomyopathy (CMi). Methods. In 29 patients with (n = 23) or without (n = 6) CMi undergoing endomyocardial biopsies (EMB), transcardiac gradients (TCGs) of circulating MSC were measured by flow cytometry from blood simultaneously sampled from aorta and coronary sinus. The presence of MSC in EMB, cardiac inflammation, and SDF-1α mRNA expression were detected via immunohistochemistry and real-time PCR. Results. MSC defined as CD45(-)CD34(-)CD11b(-)CD73(+)CD90(+) cells accounted for 0.010 [0.0025-0.048]%/peripheral mononuclear cell (PMNC) and as CD45(-)CD34(-)CD11b(-)CD73(+)CD105(+) cells for 0.019 [0.0026-0.067]%/PMNC, both with similar counts in patients with or without cardiac inflammation. There was a 29.9% (P TCG of circulating MSC and numbers of MSC (CD45(-)CD34(-)CD90(+)CD105(+)) in EMB (r = -0.73, P < 0.005). SDF-1α was the strongest predictor for increased MSC in EMB (P < 0.005, multivariate analysis). Conclusions. Endogenous MSC continuously migrate to the heart in patients with CMi triggered by cardiac inflammation. PMID:25814787

  2. Towards reduction of Paradigm coordination models

    OpenAIRE

    Andova, S.; Groenewegen, L. P. J.; Vink, de, E.P.; Aceto, Luca; Mousavi, M.R.

    2011-01-01

    The coordination modelling language Paradigm addresses collaboration between components in terms of dynamic constraints. Within a Paradigm model, component dynamics are consistently specified at a detailed and a global level of abstraction. To enable automated verification of Paradigm models, a translation of Paradigm into process algebra has been defined in previous work. In this paper we investigate, guided by a client-server example, reduction of Paradigm models based on a notion of global...

  3. Effect of human adipose tissue-derived mesenchymal-stem-cell bioactive materials on porcine embryo development.

    Science.gov (United States)

    Park, Hyo-Young; Kim, Eun-Young; Lee, Seung-Eun; Choi, Hyun-Yong; Moon, Jeremiah Jiman; Park, Min-Jee; Son, Yeo-Jin; Lee, Jun-Beom; Jeong, Chang-Jin; Lee, Dong-Sun; Riu, Key-Jung; Park, Se-Pill

    2013-12-01

    Human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) secrete bioactive materials that are beneficial for tissue repair and regeneration. In this study, we characterized human hAT-MSC bioactive material (hAT-MSC-BM), and examined the effect of hAT-MSC-BM on porcine embryo development. hAT-MSC-BM was enriched with several growth factors and cytokines, including fibroblast growth factor 2 (FGF2), vascular endothelial growth factor A (VEGFA), and interleukin 6 (IL6). Among the various concentrations and days of treatment tested, 10% hAT-MSC-BM treatment beginning on culture Day 4 provided the best environment for the in vitro growth of parthenogenetic porcine embryos. While the addition of 10% fetal bovine serum (FBS) increased the hatching rate and the total cell number of parthenogenetic porcine embryos compared with the control and hAT-MSC culture medium group, the best results were from the group cultured with 10% hAT-MSC-BM. Mitochondrial activity was also higher in the 10% hAT-MSC-BM-treated group. Moreover, the relative mRNA expression levels of development and anti-apoptosis genes were significantly higher in the 10% hAT-MSC-BM-treated group than in control, hAT-MSC culture medium, or 10% FBS groups, whereas the transcript abundance of an apoptosis gene was slightly lower. Treatment with 10% hAT-MSC-BM starting on Day 4 also improved the development rate and the total cell number of in vitro-fertilized embryos. This is the first report on the benefits of hAT-MSC-BM in a porcine embryo in vitro culture system. We conclude that hAT-MSC-BM is a new, alternative supplement that can improve the development of porcine embryos during both parthenogenesis and fertilization in vitro.

  4. Cultural Paradigms in Management Sciences

    Directory of Open Access Journals (Sweden)

    Lukasz Sulkowski

    2013-09-01

    Full Text Available Purpose: The purpose of this paper is to present an idea for understanding cultural processes in the organizational discourse from the perspective of four paradigms in management sciences based on the concept of G. Burrell and G. Morgan.Methodology: The author has elaborated a valuable list of structures of the scientifi c theory based on the respective paradigms and has compared cultural paradigms in management sciences. The methodology involves an analysis of classical and recent world literature. Nowadays there is no consensus on the defi nitions, types or research models of organizational culture.Originality: In the literature on the subject we can fi nd many, sometimes contradictory cultural research studies that require further analysis. Precisely because of the diversity and complexity of cultural issues in management sciences a multi-paradigmatic analysis is necessary. The paper presents a proposal for a pluralistic approach to the theory and methodology of cultural studies in management sciences.

  5. Mesenchymal stromal cells reset the scatter factor system and cytokine network in experimental kidney transplantation

    OpenAIRE

    Gregorini, Marilena; Bosio, Francesca; Rocca, Chiara; Corradetti, Valeria; Valsania, Teresa; Pattonieri, Eleonora Francesca; Esposito, Pasquale; Bedino, Giulia; Collesi, Chiara; Libetta, Carmelo; Frassoni, Francesco; Canton, Antonio Dal; Rampino, Teresa

    2014-01-01

    Background In former studies we showed in a rat model of renal transplantation that Mesenchymal Stromal Cells (MSC) prevent acute rejection in an independent way of their endowing in the graft. In this study we investigated whether MSC operate by resetting cytokine network and Scatter Factor systems, i.e. Hepatocyte Growth Factor (HGF), Macrophage Stimulating Protein (MSP) and their receptors Met and RON, respectively. Methods MSC were injected into the renal artery soon after reperfusion. Co...

  6. Applications of Recombinant DNA Technology in Gastrointestinal Medicine and Hepatology: Basic Paradigms of Molecular Cell Biology. Part A: Eukaryotic Gene Structure and DNA Replication

    Directory of Open Access Journals (Sweden)

    Gary E Wild

    2000-01-01

    Full Text Available Progress in the basic sciences of cell and molecular biology has provided an exciting dimension that has translated into clinically relevant information in every medical subspecialty. Importantly, the application of recombinant DNA technology has played a major role in unravelling the intricacies related to the molecular pathophysiology of disease. This series of review articles constitutes a framework for the integration of the database of new information into the core knowledge base of concepts related to the pathogenesis of gastrointestinal disorders and liver disease. The goal of this series of three articles is to review the basic principles of eukaryotic gene expression. The first article examines the role of DNA in directing the flow of genetic information in eukaryotic cells.

  7. Applications of Recombinant DNA Technology in Gastrointestinal Medicine and Hepatology: Basic Paradigms of Molecular Cell Biology. Part A: Eukaryotic Gene Structure and DNA Replication

    OpenAIRE

    Wild, Gary E; Papalia, Patrizia; Ropeleski, Mark J.; Faria, Julio; Thomson, Alan BR

    2000-01-01

    Progress in the basic sciences of cell and molecular biology has provided an exciting dimension that has translated into clinically relevant information in every medical subspecialty. Importantly, the application of recombinant DNA technology has played a major role in unravelling the intricacies related to the molecular pathophysiology of disease. This series of review articles constitutes a framework for the integration of the database of new information into the core knowledge base of conc...

  8. Applications of Recombinant Dna Technology in Gastrointestinal Medicine and Hepatology: Basic Paradigms of Molecular Cell Biology. Part B: Eukaryotic Gene Transcription and Post-Transcripional Rna Processing

    Directory of Open Access Journals (Sweden)

    Gary E Wild

    2000-01-01

    Full Text Available The transcription of DNA into RNA is the primary level at which gene expression is controlled in eukaryotic cells. Eukaryotic gene transcription  involves several different RNA polymerases that interact with a host of transcription factors to initiate transcription. Genes that encode proteins are transcribed into messenger RNA (mRNA by RNA polymerase II. Ribosomal RNAs (rRNAs and transfer RNAs (tRNAs are transcribed by RNA polymerase I and III, respectively.  The production of each mRNA in human cells involves complex interactions of proteins (ie, trans-acting factors with specific sequences on the DNA (ie, cis-acting elements. Cis-acting elements are short base sequences adjacent to or within a particular gene. While the regulation of transcription is a pivotal step in the control of gene expression, a variety of molecular events, collectively known as ’RNA processing’  add an additional level of control of gene expression in eukaryotic cells.

  9. Mesenchymal stem cell therapy in proteoglycan induced arthritis

    NARCIS (Netherlands)

    Swart, J. F.; de Roock, S.; Hofhuis, F. M.; Rozemuller, H.; van den Broek, T.; Moerer, P.; Broere, F.; van Wijk, F.; Kuis, W.; Prakken, B. J.; Martens, a.c.m; Wulffraat, N. M.

    2015-01-01

    Objectives: To explore the immunosuppressive effect and mechanism of action of intraperitoneal (ip) and intra-articular (ia) mesenchymal stem cell (MSC) injection in proteoglycan induced arthritis (PGIA). Methods: MSC were administered ip or ia after establishment of arthritis. We used serial biolum

  10. Degenerate wave and capacitive coupling increase human MSC invasion and proliferation while reducing cytotoxicity in an in vitro wound healing model.

    Directory of Open Access Journals (Sweden)

    Michelle Griffin

    Full Text Available Non-unions pose complications in fracture management that can be treated using electrical stimulation (ES. Bone marrow mesenchymal stem cells (BMMSCs are essential in fracture healing; however, the effect of different clinical ES waveforms on BMMSCs cellular activities remains unknown. We compared the effects of direct current (DC, capacitive coupling (CC, pulsed electromagnetic field (PEMF and degenerate wave (DW on cellular activities including cytotoxicity, proliferation, cell-kinetics and apoptosis by stimulating human-BMMSCs 3 hours a day, up to 5 days. In addition, migration and invasion were assessed using fluorescence microscopy and by quantifying gene and protein expression. We found that DW had the greatest proliferative and least apoptotic and cytotoxic effects compared to other waveforms. DC, DW and CC stimulations resulted in a higher number of cells in S phase and G(2/M phase as shown by cell cycle analysis. CC and DW caused more cells to invade collagen and showed increased MMP-2 and MT1-MMP expression. DC increased cellular migration in a scratch-wound assay and all ES waveforms enhanced expression of migratory genes with DC having the greatest effect. All ES treated cells showed similar progenitor potential as determined by MSC differentiation assay. All above findings were shown to be statistically significant (p<0.05. We conclude that ES can influence BMMSCs activities, especially DW and CC, which show greater invasion and higher cell proliferation compared to other types of ES. Application of DW or CC to the fracture site may help in the recruitment of BMMSCs to the wound that may enhance rate of bone healing at the fracture site.

  11. Bayesian test and Kuhn's paradigm

    Institute of Scientific and Technical Information of China (English)

    Chen Xiaoping

    2006-01-01

    Kuhn's theory of paradigm reveals a pattern of scientific progress,in which normal science alternates with scientific revolution.But Kuhn underrated too much the function of scientific test in his pattern,because he focuses all his attention on the hypothetico-deductive schema instead of Bayesian schema.This paper employs Bayesian schema to re-examine Kuhn's theory of paradigm,to uncover its logical and rational components,and to illustrate the tensional structure of logic and belief,rationality and irrationality,in the process of scientific revolution.

  12. The synthesis paradigm in genetics.

    Science.gov (United States)

    Rice, William R

    2014-02-01

    Experimental genetics with model organisms and mathematically explicit genetic theory are generally considered to be the major paradigms by which progress in genetics is achieved. Here I argue that this view is incomplete and that pivotal advances in genetics--and other fields of biology--are also made by synthesizing disparate threads of extant information rather than generating new information from experiments or formal theory. Because of the explosive expansion of information in numerous "-omics" data banks, and the fragmentation of genetics into numerous subdisciplines, the importance of the synthesis paradigm will likely expand with time.

  13. Transmission pricing: paradigms and methodologies

    Energy Technology Data Exchange (ETDEWEB)

    Shirmohammadi, Dariush [Pacific Gas and Electric Co., San Francisco, CA (United States); Vieira Filho, Xisto; Gorenstin, Boris [Centro de Pesquisas de Energia Eletrica (CEPEL), Rio de Janeiro, RJ (Brazil); Pereira, Mario V.P. [Power System Research, Rio de Janeiro, RJ (Brazil)

    1994-12-31

    In this paper we describe the principles of several paradigms and methodologies for pricing transmission services. The paper outlines some of the main characteristics of these paradigms and methodologies such as where they may be used for best results. Due to their popularity, power flow based MW-mile and short run marginal cost pricing methodologies will be covered in some detail. We conclude the paper with examples of the application of these two pricing methodologies for pricing transmission services in Brazil. (author) 25 refs., 2 tabs.

  14. Paradigms in Physics Education Research

    CERN Document Server

    Robertson, Amy D; McKagan, Sarah B

    2013-01-01

    Physics education research (PER) includes three distinct paradigms: quantitative research, qualitative research, and question-driven research. Quantitative PER seeks reproducible, representative patterns and relationships; human behavior is seen as dictated by lawful (albeit probabilistic) relationships. Qualitative PER seeks to refine and develop theory by linking theory to cases; human action is seen as shaped by the meanings that participants make of their local environments. Question-driven physics education researchers prioritize questions over the pursuit of local meanings or abstract relationships. We illustrate each paradigm with interviews with physics education researchers and examples of published PER.

  15. Shifting the paradigm

    DEFF Research Database (Denmark)

    Kiss, Katalin; Brozik, Anna; Kucsma, Nora;

    2012-01-01

    ABCB6, a member of the adenosine triphosphate-binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticuloc......ABCB6, a member of the adenosine triphosphate-binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from...... reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cells. Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis...

  16. Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss

    DEFF Research Database (Denmark)

    Bellantuono, Ilaria; Aldahmash, Abdullah; Kassem, Moustapha

    2009-01-01

    Marrow stromal cells (MSC) are thought to be stem cells with osteogenic potential and therefore responsible for the repair and maintenance of the skeleton. Age related bone loss is one of the most prevalent diseases in the elder population. It is controversial whether MSC undergo a process of aging...

  17. Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer.

    Science.gov (United States)

    Ji, Runbi; Zhang, Bin; Zhang, Xu; Xue, Jianguo; Yuan, Xiao; Yan, Yongmin; Wang, Mei; Zhu, Wei; Qian, Hui; Xu, Wenrong

    2015-08-01

    Mesenchymal stem cells (MSCs) play an important role in chemoresistance. Exosomes have been reported to modify cellular phenotype and function by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from MSCs (MSC-exosomes) are involved in mediating the resistance to chemotherapy in gastric cancer and to explore the underlying molecular mechanism. We found that MSC-exosomes significantly induced the resistance of gastric cancer cells to 5-fluorouracil both in vivo and ex vivo. MSC-exosomes antagonized 5-fluorouracil-induced apoptosis and enhanced the expression of multi-drug resistance associated proteins, including MDR, MRP and LRP. Mechanistically, MSC-exosomes triggered the activation of calcium/calmodulin-dependent protein kinases (CaM-Ks) and Raf/MEK/ERK kinase cascade in gastric cancer cells. Blocking the CaM-Ks/Raf/MEK/ERK pathway inhibited the promoting role of MSC-exosomes in chemoresistance. Collectively, MSC-exosomes could induce drug resistance in gastric cancer cells by activating CaM-Ks/Raf/MEK/ERK pathway. Our findings suggest that MSC-exosomes have profound effects on modifying gastric cancer cells in the development of drug resistance. Targeting the interaction between MSC-exosomes and cancer cells may help improve the efficacy of chemotherapy in gastric cancer.

  18. Tissue distribution and engraftment of human mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene

    DEFF Research Database (Denmark)

    Bentzon, J F; Stenderup, K; Hansen, F D;

    2005-01-01

    Engraftment of mesenchymal stem cells (MSC) in peripheral tissues for replenishing of local stem cell function has been proposed as a therapeutic approach to degenerative diseases. We have previously reported the development of an immortalized human telomerase reverse transcriptase transduced MSC...

  19. Modulation of human mesenchymal stem cell immunogenicity through forced expression of human cytomegalovirus us proteins.

    Directory of Open Access Journals (Sweden)

    Melisa A Soland

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSC are promising candidates for cell therapy, as they migrate to areas of injury, differentiate into a broad range of specialized cells, and have immunomodulatory properties. However, MSC are not invisible to the recipient's immune system, and upon in vivo administration, allogeneic MSC are able to trigger immune responses, resulting in rejection of the transplanted cells, precluding their full therapeutic potential. Human cytomegalovirus (HCMV has developed several strategies to evade cytotoxic T lymphocyte (CTL and Natural Killer (NK cell recognition. Our goal is to exploit HCMV immunological evasion strategies to reduce MSC immunogenicity. METHODOLOGY/PRINCIPAL FINDINGS: We genetically engineered human MSC to express HCMV proteins known to downregulate HLA-I expression, and investigated whether modified MSC were protected from CTL and NK attack. Flow cytometric analysis showed that amongst the US proteins tested, US6 and US11 efficiently reduced MSC HLA-I expression, and mixed lymphocyte reaction demonstrated a corresponding decrease in human and sheep mononuclear cell proliferation. NK killing assays showed that the decrease in HLA-I expression did not result in increased NK cytotoxicity, and that at certain NK∶MSC ratios, US11 conferred protection from NK cytotoxic effects. Transplantation of MSC-US6 or MSC-US11 into pre-immune fetal sheep resulted in increased liver engraftment when compared to control MSC, as demonstrated by qPCR and immunofluorescence analyses. CONCLUSIONS AND SIGNIFICANCE: These data demonstrate that engineering MSC to express US6 and US11 can be used as a means of decreasing recognition of MSC by the immune system, allowing higher levels of engraftment in an allogeneic transplantation setting. Since one of the major factors responsible for the failure of allogeneic-donor MSC to engraft is the mismatch of HLA-I molecules between the donor and the recipient, MSC-US6 and MSC-US11

  20. Prospect of Stem Cells in Bone Tissue Engineering: A Review

    Directory of Open Access Journals (Sweden)

    Azizeh-Mitra Yousefi

    2016-01-01

    Full Text Available Mesenchymal stem cells (MSCs have been the subject of many studies in recent years, ranging from basic science that looks into MSCs properties to studies that aim for developing bioengineered tissues and organs. Adult bone marrow-derived mesenchymal stem cells (BM-MSCs have been the focus of most studies due to the inherent potential of these cells to differentiate into various cell types. Although, the discovery of induced pluripotent stem cells (iPSCs represents a paradigm shift in our understanding of cellular differentiation. These cells are another attractive stem cell source because of their ability to be reprogramed, allowing the generation of multiple cell types from a single cell. This paper briefly covers various types of stem cell sources that have been used for tissue engineering applications, with a focus on bone regeneration. Then, an overview of some recent studies making use of MSC-seeded 3D scaffold systems for bone tissue engineering has been presented. The emphasis has been placed on the reported scaffold properties that tend to improve MSCs adhesion, proliferation, and osteogenic differentiation outcomes.

  1. Sympathetic Denervation-Induced MSC Mobilization in Distraction Osteogenesis Associates with Inhibition of MSC Migration and Osteogenesis by Norepinephrine/adrb3

    OpenAIRE

    Du, Zhaojie; Wang, Lei; Zhao, Yinghua; Cao, Jian; Tao WANG; Liu, Peng; Zhang, Yabo; Yang, Xinjie; Cheng, Xiaobing; Liu, Baolin; Lei, Delin

    2014-01-01

    The sympathetic nervous system regulates bone formation and resorption under physiological conditions. However, it is still unclear how the sympathetic nerves affect stem cell migration and differentiation in bone regeneration. Distraction osteogenesis is an ideal model of bone regeneration due to its special nature as a self-engineering tissue. In this study, a rat model of mandibular distraction osteogenesis with transection of cervical sympathetic trunk was used to demonstrate that sympath...

  2. Hypoxia Created Human Mesenchymal Stem Cell Sheet for Prevascularized 3D Tissue Construction.

    Science.gov (United States)

    Zhang, Lijun; Xing, Qi; Qian, Zichen; Tahtinen, Mitchell; Zhang, Zhaoqiang; Shearier, Emily; Qi, Shaohai; Zhao, Feng

    2016-02-01

    3D tissue based on human mesenchymal stem cell (hMSC) sheets offers many interesting opportunities for regenerating multiple types of connective tissues. Prevascularizing hMSC sheets with endothelial cells (ECs) will improve 3D tissue performance by supporting cell survival and accelerating integration with host tissue. It is hypothesized that hypoxia cultured hMSC sheets can promote microvessel network formation and preserve stemness of hMSCs. This study investigates the vascularization of hMSC sheets under different oxygen tensions. It is found that the HN condition, in which hMSC sheets formed under physiological hypoxia (2% O2 ) and then cocultured with ECs under normoxia (20% O2 ), enables longer and more branched microvessel network formation. The observation is corroborated by higher levels of angiogenic factors in coculture medium. Additionally, the hypoxic hMSC sheet is more uniform and less defective, which facilitates fabrication of 3D prevascularized tissue construct by layering the prevascularized hMSC sheets and maturing in rotating wall vessel bioreactor. The hMSCs in the 3D construct still maintain multilineage differentiation ability, which indicates the possible application of the 3D construct for various connective tissues regeneration. These results demonstrate that hypoxia created hMSC sheets benefit the microvessel growth and it is feasible to construct 3D prevascularized tissue construct using the prevascularized hMSC sheets.

  3. Tissue Regeneration of the Vocal Fold Using Bone Marrow Mesenchymal Stem Cells and Synthetic Extracellular Matrix Injections in Rats

    Science.gov (United States)

    Johnson, Beatriz Helena Quinchia; Fox, Ryan; Chen, Xia; Thibeault, Susan

    2009-01-01

    Objective To determine the effectiveness of bone marrow mesenchymal stem cell (BM-MSC) transplantation in isolation or within a synthetic extracellular matrix (sECM) for tissue regeneration of the scarred vocal fold lamina propria. Methods In vitro stability and compatibility of mouse BM-MSC embedded in sECM was assessed by flow cytometry detection of BM-MSC marker expression and proliferation. Eighteen rats were subjected to vocal fold injury bilaterally, followed by one month post-treatment with unilateral injections of saline or sECM hydrogel (Extracel), GFP-mouse BM-MSC or BM-MSC suspended in sECM. Outcomes measured one month after treatment included procollagen-III, fibronectin, hyaluronan synthase-III (HAS3), hyaluronidase (HYAL3), smooth muscle actin (SMA) and transforming growth factor-beta 1(TGF-β1) mRNA expression. The persistence of GFP BM-MSC, proliferation, apoptosis and myofibroblast differentiation was assessed by immunofluorescence. Results BM-MSC grown in vitro within sECM express Sca-1, are positive for hyaluronan receptor CD44 and continue to proliferate. In the in vivo study, groups injected with BM-MSC had detectable GFP-labeled BM-MSC remaining, showed proliferation and low apoptotic or myofibroblast markers compared to the contralateral side. Embedded BM-MSC in sECM group exhibited increased levels of procollagen III, fibronectin and TGF-β1. BM-MSC within sECM downregulated the expression of SMA compared to BM-MSC alone, exhibited upregulation of HYAL3 and no change in HAS3 compared to saline. Conclusions Treatment of vocal fold scarring with BM-MSC injected in a sECM displayed the most favorable outcomes in ECM production, hyaluronan metabolism, myofibroblast differentiation and production of TGF-β1. Furthermore, the combined treatment had no detectable cytotoxicity and preserved local cell proliferation. PMID:20131370

  4. The Paradigm of Distributed Creativity

    DEFF Research Database (Denmark)

    Glaveanu, Vlad Petre

    This presentation aims to focus on and develop the notion of distributed creativity from a cultural psychological perspective. It will start by outlining the need for a cultural psychological paradigm of creative expression and argue that this perspective is primarily concerned with what can...

  5. Explaining (Missing) Regulator Paradigm Shifts

    DEFF Research Database (Denmark)

    Wigger, Angela; Buch-Hansen, Hubert

    2014-01-01

    of competition regulation is heaving into sight. It sets out to explain this from the vantage point of a critical political economy perspective, which identifies the circumstances under which a crisis can result in a regulatory paradigm shift. Contrasting the current situation with the shift in EC/EU competition...

  6. A paradigm shift in EPH receptor interaction: biological relevance of EPHB6 interaction with EPHA2 and EPHB2 in breast carcinoma cell lines.

    Science.gov (United States)

    Fox, Brian P; Kandpal, Raj P

    2011-01-01

    EPH receptors are the largest known family of receptor tyrosine kinases characterized in humans. These proteins are involved in axon guidance, tissue organization, synaptic plasticity, vascular development and the progression of various diseases including cancer. The varied biological effects of EPH receptors are mediated in part by the expression of these proteins and their intracellular binding proteins. The ability of EPH molecules to form heterodimers within their own class has been suggested, although not exhaustively characterized. We have clarified this phenomenon by showing that EPHB6, a kinase-deficient receptor, can interact with EPHB2 in mammalian cells, and more significantly EPHB6 interacts with EPHA2. However, EPHB6 does not interact with another kinase-deficient receptor, EPHA10. The interaction between EPHB6 and EPHA2 is the first demonstration of an A-type receptor interacting with a B-type receptor. Furthermore, we correlated relative expression of EPHB6, EPHB2 and EPHA2 with non-invasive and invasive phenotypes of breast tumor cell lines. Our results indicate that tumor invasiveness-suppressing activity of EPHB6 is mediated by its ability to sequester other kinase-sufficient and oncogenic EPH receptors. These observations suggest that cellular phenotypes may, in part, be attributed to a combinatorial expression of EPH receptors and heteromeric interactions among the same class, as well as between two classes, of EPH receptors. Our results also suggest that EPHA10 may transduce signals by interacting with other kinase-sufficient receptors in a similar manner. PMID:21737611

  7. [Recent Advances on the Immunoregulation of MicroRNA-155 in Mesenchymal Stem Cells--Review].

    Science.gov (United States)

    Han, Xiao; Wang, Lei; Wu, Tao; Bai, Hai

    2016-02-01

    Mesenchymal stem cells (MSC) are capable of immunosuppression and differentiating into multiple cell lineages. MSC, which are accessed easily and less side-effects, have been a source of seed cells in tissue-engineering and cell-therapy. However, the application of MSC are limited by their differentiation of instability and easy aging. MicroRNA-155 (miR-155) is one of microRNA, which has powerful regulatory potential in a wide variety of immune cells through degrading specific mRNA after transcription and inhibiting translation of the target genes. Following the research of miR-155 deeply, it has an indispensable role in the proliferation, differentiation and immunoregulation of MSC. This review discusses the current understandings for the role of miR-155 in MSC.

  8. MSC Adams在双前桥转向机构设计中的应用%Application of MSC Adams in Design of Steering Mechanism of Double-Front Axle

    Institute of Scientific and Technical Information of China (English)

    吕召全; 华从波; 周福庚

    2006-01-01

    本论文对双前桥载货汽车的转向机构进行了全新的设计,在理论计算的基础上利用MSC Adams软件分别对转向梯形和转向摇臂机构进行了运动学仿真,并对其转向特性进行了优化. 随后的道路试验结果表明新设计的转向机构性能符合设计要求.

  9. Partial suppression of the respiratory defect of qrs1/her2 glutamyl-tRNA amidotransferase mutants by overexpression of the mitochondrial pentatricopeptide Msc6p.

    Science.gov (United States)

    Moda, Bruno S; Ferreira-Júnior, José Ribamar; Barros, Mario H

    2016-08-01

    Recently, a large body of evidences indicates the existence in the mitochondrial matrix of foci that contain different proteins involved in mitochondrial RNA metabolism. Some of these proteins have a pentatricopeptide repeat motif that constitutes their RNA-binding structures. Here we report that MSC6, a mitochondrial pentatricopeptide protein of unknown function, is a multi copy suppressor of mutations in QRS1/HER2 a component of the trimeric complex that catalyzes the transamidation of glutamyl-tRNAQ to glutaminyl-tRNAQ. This is an essential step in mitochondrial translation because of the lack of a specific mitochondrial aminoacyl glutaminyl-tRNA synthetase. MSC6 over-expression did not abolish translation of an aberrant variant form of Cox2p detected in QRS1/HER2 mutants, arguing against a suppression mechanism that bypasses Qrs1p function. A slight decrement of the mitochondrial translation capacity as well as diminished growth on respiratory carbon sources media for respiratory activity was observed in the msc6 null mutant. Additionally, the msc6 null mutant did not display any impairment in RNA transcription, processing or turnover. We concluded that Msc6p is a mitochondrial matrix protein and further studies are required to indicate the specific function of Msc6p in mitochondrial translation. PMID:26780366

  10. Partial suppression of the respiratory defect of qrs1/her2 glutamyl-tRNA amidotransferase mutants by overexpression of the mitochondrial pentatricopeptide Msc6p.

    Science.gov (United States)

    Moda, Bruno S; Ferreira-Júnior, José Ribamar; Barros, Mario H

    2016-08-01

    Recently, a large body of evidences indicates the existence in the mitochondrial matrix of foci that contain different proteins involved in mitochondrial RNA metabolism. Some of these proteins have a pentatricopeptide repeat motif that constitutes their RNA-binding structures. Here we report that MSC6, a mitochondrial pentatricopeptide protein of unknown function, is a multi copy suppressor of mutations in QRS1/HER2 a component of the trimeric complex that catalyzes the transamidation of glutamyl-tRNAQ to glutaminyl-tRNAQ. This is an essential step in mitochondrial translation because of the lack of a specific mitochondrial aminoacyl glutaminyl-tRNA synthetase. MSC6 over-expression did not abolish translation of an aberrant variant form of Cox2p detected in QRS1/HER2 mutants, arguing against a suppression mechanism that bypasses Qrs1p function. A slight decrement of the mitochondrial translation capacity as well as diminished growth on respiratory carbon sources media for respiratory activity was observed in the msc6 null mutant. Additionally, the msc6 null mutant did not display any impairment in RNA transcription, processing or turnover. We concluded that Msc6p is a mitochondrial matrix protein and further studies are required to indicate the specific function of Msc6p in mitochondrial translation.

  11. Cardiomyocyte protection by GATA-4 gene engineered mesenchymal stem cells is partially mediated by translocation of miR-221 in microvesicles.

    Directory of Open Access Journals (Sweden)

    Bin Yu

    Full Text Available INTRODUCTION: microRNAs (miRs, a novel class of small non-coding RNAs, are involved in cell proliferation, differentiation, development, and death. In this study, we found that miR-221 translocation by microvesicles (MVs plays an important role in cardioprotection mediated by GATA-4 overexpressed mesenchymal stem cells (MSC. METHODS AND RESULTS: Adult rat bone marrow MSC and neonatal rat ventricle cardiomyocytes (CM were harvested as primary cultures. MSC were transduced with GATA-4 (MSC(GATA-4 using the murine stem cell virus (pMSCV retroviral expression system. Empty vector transfection was used as a control (MSC(Null. The expression of miRs was assessed by real-time PCR and localized using in situ hybridization (ISH. MVs collected from MSC cultures were characterized by expression of CD9, CD63, and HSP70, and photographed with electron microscopy. Cardioprotection during hypoxia afforded by conditioned medium (CdM from MSC cultures was evaluated by lactate dehydrogenase (LDH release, MTS uptake by CM, and caspase 3/7 activity. Expression of miR-221/222 was significantly higher in MSC than in CM and miR-221 was upregulated in MSC(GATA-4. MSC overexpression of miR-221 significantly enhanced cardioprotection by reducing the expression of p53 upregulated modulator of apoptosis (PUMA. Moreover, expression of PUMA was significantly decreased in CM co-cultured with MSC. MVs derived from MSC expressed high levels of miR-221, and were internalized quickly by CM as documented in images obtained from a Time-Lapse Imaging System. CONCLUSIONS: Our results demonstrate that cardioprotection by MSC(GATA-4 may be regulated in part by a transfer of anti-apoptotic miRs contained within MVs.

  12. Mitochondrial Transfer via Tunneling Nanotubes is an Important Mechanism by Which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the In Vitro and In Vivo Models of ARDS

    Science.gov (United States)

    Jackson, Megan V.; Morrison, Thomas J.; Doherty, Declan F.; McAuley, Daniel F.; Matthay, Michael A.; Kissenpfennig, Adrien; O'Kane, Cecilia M.

    2016-01-01

    Abstract Mesenchymal stromal cells (MSC) have been reported to improve bacterial clearance in preclinical models of Acute Respiratory Distress Syndrome (ARDS) and sepsis. The mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the antimicrobial effect of MSC in vivo depends on their modulation of macrophage phagocytic activity which occurs through mitochondrial transfer. We established that selective depletion of alveolar macrophages (AM) with intranasal (IN) administration of liposomal clodronate resulted in complete abrogation of MSC antimicrobial effect in the in vivo model of Escherichia coli pneumonia. Furthermore, we showed that MSC administration was associated with enhanced AM phagocytosis in vivo. We showed that direct coculture of MSC with monocyte‐derived macrophages enhanced their phagocytic capacity. By fluorescent imaging and flow cytometry we demonstrated extensive mitochondrial transfer from MSC to macrophages which occurred at least partially through tunneling nanotubes (TNT)‐like structures. We also detected that lung macrophages readily acquire MSC mitochondria in vivo, and macrophages which are positive for MSC mitochondria display more pronounced phagocytic activity. Finally, partial inhibition of mitochondrial transfer through blockage of TNT formation by MSC resulted in failure to improve macrophage bioenergetics and complete abrogation of the MSC effect on macrophage phagocytosis in vitro and the antimicrobial effect of MSC in vivo. Collectively, this work for the first time demonstrates that mitochondrial transfer from MSC to innate immune cells leads to enhancement in phagocytic activity and reveals an important novel mechanism for the antimicrobial effect of MSC in ARDS. Stem Cells 2016;34:2210–2223 PMID:27059413

  13. Mitochondrial Transfer via Tunneling Nanotubes is an Important Mechanism by Which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the In Vitro and In Vivo Models of ARDS.

    Science.gov (United States)

    Jackson, Megan V; Morrison, Thomas J; Doherty, Declan F; McAuley, Daniel F; Matthay, Michael A; Kissenpfennig, Adrien; O'Kane, Cecilia M; Krasnodembskaya, Anna D

    2016-08-01

    Mesenchymal stromal cells (MSC) have been reported to improve bacterial clearance in preclinical models of Acute Respiratory Distress Syndrome (ARDS) and sepsis. The mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the antimicrobial effect of MSC in vivo depends on their modulation of macrophage phagocytic activity which occurs through mitochondrial transfer. We established that selective depletion of alveolar macrophages (AM) with intranasal (IN) administration of liposomal clodronate resulted in complete abrogation of MSC antimicrobial effect in the in vivo model of Escherichia coli pneumonia. Furthermore, we showed that MSC administration was associated with enhanced AM phagocytosis in vivo. We showed that direct coculture of MSC with monocyte-derived macrophages enhanced their phagocytic capacity. By fluorescent imaging and flow cytometry we demonstrated extensive mitochondrial transfer from MSC to macrophages which occurred at least partially through tunneling nanotubes (TNT)-like structures. We also detected that lung macrophages readily acquire MSC mitochondria in vivo, and macrophages which are positive for MSC mitochondria display more pronounced phagocytic activity. Finally, partial inhibition of mitochondrial transfer through blockage of TNT formation by MSC resulted in failure to improve macrophage bioenergetics and complete abrogation of the MSC effect on macrophage phagocytosis in vitro and the antimicrobial effect of MSC in vivo. Collectively, this work for the first time demonstrates that mitochondrial transfer from MSC to innate immune cells leads to enhancement in phagocytic activity and reveals an important novel mechanism for the antimicrobial effect of MSC in ARDS. Stem Cells 2016;34:2210-2223.

  14. Pretreatment of Cardiac Stem Cells With Exosomes Derived From Mesenchymal Stem Cells Enhances Myocardial Repair

    OpenAIRE

    Zhang, Zhiwei; Yang, Junjie; Yan, Weiya; Li, Yangxin; Shen, Zhenya; Asahara, Takayuki

    2016-01-01

    Background Exosomes derived from mesenchymal stem cells (MSCs) were proved to boost cell proliferation and angiogenic potency. We explored whether cardiac stem cells (CSCs) preconditioned with MSC exosomes could survive and function better in a myocardial infarction model. Methods and Results DiI‐labeled exosomes were internalized with CSCs. They stimulated proliferation, migration, and angiotube formation of CSCs in a dose‐dependent manner. In a rat myocardial infarction model, MSC exosome–p...

  15. Defining the role of mesenchymal stromal cells on the regulation of matrix metalloproteinases in skeletal muscle cells

    International Nuclear Information System (INIS)

    Recent studies indicate that mesenchymal stromal cell (MSC) transplantation improves healing of injured and diseased skeletal muscle, although the mechanisms of benefit are poorly understood. In the present study, we investigated whether MSCs and/or their trophic factors were able to regulate matrix metalloproteinase (MMP) expression and activity in different cells of the muscle tissue. MSCs in co-culture with C2C12 cells or their conditioned medium (MSC-CM) up-regulated MMP-2 and MMP-9 expression and function in the myoblastic cells; these effects were concomitant with the down-regulation of the tissue inhibitor of metalloproteinases (TIMP)-1 and -2 and with increased cell motility. In the single muscle fiber experiments, MSC-CM administration increased MMP-2/9 expression in Pax-7+ satellite cells and stimulated their mobilization, differentiation and fusion. The anti-fibrotic properties of MSC-CM involved also the regulation of MMPs by skeletal fibroblasts and the inhibition of their differentiation into myofibroblasts. The treatment with SB-3CT, a potent MMP inhibitor, prevented in these cells, the decrease of α-smooth actin and type-I collagen expression induced by MSC-CM, suggesting that MSC-CM could attenuate the fibrogenic response through mechanisms mediated by MMPs. Our results indicate that growth factors and cytokines released by these cells may modulate the fibrotic response and improve the endogenous mechanisms of muscle repair/regeneration. - Highlights: • MSC-CM contains paracrine factors that up-regulate MMP expression and function in different skeletal muscle cells. • MSC-CM promotes myoblast and satellite cell migration, proliferation and differentiation. • MSC-CM negatively interferes with fibroblast-myoblast transition in primary skeletal fibroblasts. • Paracrine factors from MSCs modulate the fibrotic response and improve the endogenous mechanisms of muscle regeneration

  16. Defining the role of mesenchymal stromal cells on the regulation of matrix metalloproteinases in skeletal muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Sassoli, Chiara; Nosi, Daniele; Tani, Alessia; Chellini, Flaminia [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Mazzanti, Benedetta [Dept. of Experimental and Clinical Medicine—Section of Haematology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Quercioli, Franco [CNR-National Institute of Optics (INO), Largo Enrico Fermi 6, 50125 Arcetri-Florence (Italy); Zecchi-Orlandini, Sandra [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy); Formigli, Lucia, E-mail: formigli@unifi.it [Dept. of Experimental and Clinical Medicine—Section of Anatomy and Histology, University of Florence, Largo Brambilla, 3, 50134, Florence (Italy)

    2014-05-01

    Recent studies indicate that mesenchymal stromal cell (MSC) transplantation improves healing of injured and diseased skeletal muscle, although the mechanisms of benefit are poorly understood. In the present study, we investigated whether MSCs and/or their trophic factors were able to regulate matrix metalloproteinase (MMP) expression and activity in different cells of the muscle tissue. MSCs in co-culture with C2C12 cells or their conditioned medium (MSC-CM) up-regulated MMP-2 and MMP-9 expression and function in the myoblastic cells; these effects were concomitant with the down-regulation of the tissue inhibitor of metalloproteinases (TIMP)-1 and -2 and with increased cell motility. In the single muscle fiber experiments, MSC-CM administration increased MMP-2/9 expression in Pax-7{sup +} satellite cells and stimulated their mobilization, differentiation and fusion. The anti-fibrotic properties of MSC-CM involved also the regulation of MMPs by skeletal fibroblasts and the inhibition of their differentiation into myofibroblasts. The treatment with SB-3CT, a potent MMP inhibitor, prevented in these cells, the decrease of α-smooth actin and type-I collagen expression induced by MSC-CM, suggesting that MSC-CM could attenuate the fibrogenic response through mechanisms mediated by MMPs. Our results indicate that growth factors and cytokines released by these cells may modulate the fibrotic response and improve the endogenous mechanisms of muscle repair/regeneration. - Highlights: • MSC-CM contains paracrine factors that up-regulate MMP expression and function in different skeletal muscle cells. • MSC-CM promotes myoblast and satellite cell migration, proliferation and differentiation. • MSC-CM negatively interferes with fibroblast-myoblast transition in primary skeletal fibroblasts. • Paracrine factors from MSCs modulate the fibrotic response and improve the endogenous mechanisms of muscle regeneration.

  17. Human Stromal (Mesenchymal) Stem Cells from Bone Marrow, Adipose Tissue and Skin Exhibit Differences in Molecular Phenotype and Differentiation Potential

    DEFF Research Database (Denmark)

    Al-Nbaheen, May; Vishnubalaji, Radhakrishnan; Ali, Dalia;

    2013-01-01

    Human stromal (mesenchymal) stem cells (hMSCs) are multipotent stem cells with ability to differentiate into mesoderm-type cells e.g. osteoblasts and adipocytes and thus they are being introduced into clinical trials for tissue regeneration. Traditionally, hMSCs have been isolated from bone marrow......, but the number of cells obtained is limited. Here, we compared the MSC-like cell populations, obtained from alternative sources for MSC: adipose tissue and skin, with the standard phenotype of human bone marrow MSC (BM-MSCs). MSC from human adipose tissue (human adipose stromal cells (hATSCs)) and human skin......, MSC populations obtained from different tissues exhibit significant differences in their proliferation, differentiation and molecular phenotype, which should be taken into consideration when planning their use in clinical protocols....

  18. [Distribution of compact bone mesenchymal stem cells in lung tissue and bone marrow of mouse].

    Science.gov (United States)

    Wang, Rui-Ping; Wu, Ren-Na; Guo, Yu-Qing; Zhang, Bin; Chen, Hu

    2014-02-01

    This study was aimed to investigate the distribution of compact bone mesenchymal stem cells(MSC) marked with lentiviral plasmid pGC FU-RFP-LV in lung tissue and bone marrow of mouse. The MSC were infected by lentivirus with infection efficiency 78%, the infected MSC were injected into BALB/c mice via tail veins in concentration of 1×10(6) /mouse. The mice were randomly divided into 4 group according to 4 time points as 1, 2, 5 and 7 days. The lung tissue and bone marrow were taken and made of frozen sections and smears respectively in order to observed the distributions of MSC. The results indicated that the lentiviral infected MSC displayed phenotypes and biological characteristics which conformed to MSC by immunophenotyping analysis and induction differentiation detection. After the MSC were infected with optimal viral titer MOI = 50, the cell growth no significantly changed; the fluorescent microscopy revealed that the distributions of MSC in bone marrow on day 1, 2, 5 and 7 were 0.50 ± 0.20, 0.67 ± 0.23, 0.53 ± 0.14, 0.33 ± 0.16; those in lung tissue were 0.55 ± 0.15, 0.47 ± 0.13, 0.29 ± 0.13, 0.26 ± 0.08. It is concluded that the distribution of MSC in lung tissue reaches a peak on day 1, while distribution of MSC in bone marrow reaches a peak on day 2. The distribution of mouse MSC relates with RFP gene expression and implantation of MSC in lung tissue and bone marrow.

  19. M-Learning: A New Paradigm of Learning Mathematics in Malaysia

    CERN Document Server

    Mahamad, Saipunidzam; Taib, Shakirah Mohd; 10.5121/ijcsit.2010.2407

    2010-01-01

    M-Learning is a new learning paradigm of the new social structure with mobile and wireless technologies.Smart school is one of the four flagship applications for Multimedia Super Corridor (MSC) under Malaysian government initiative to improve education standard in the country. With the advances of mobile devices technologies, mobile learning could help the government in realizing the initiative. This paper discusses the prospect of implementing mobile learning for primary school students. It indicates significant and challenges and analysis of user perceptions on potential mobile applications through a survey done in primary school context. The authors propose the m-Learning for mathematics by allowing the extension of technology in the traditional classroom in term of learning and teaching.

  20. M-Learning: A New Paradigm of Learning Mathematics in Malaysia

    Directory of Open Access Journals (Sweden)

    Saipunidzam Mahamad

    2010-09-01

    Full Text Available M-Learning is a new learning paradigm of the new social structure with mobile and wireless technologies.Smart school is one of the four flagship applications for Multimedia Super Corridor (MSC underMalaysian government initiative to improve education standard in the country. With the advances ofmobile devices technologies, mobile learning could help the government in realizing the initiative. Thispaper discusses the prospect of implementing mobile learning for primary school students. It indicatessignificant and challenges and analysis of user perceptions on potential mobile applications through asurvey done in primary school context. The authors propose the m-Learning for mathematics by allowingthe extension of technology in the traditional classroom in term of learning and teaching

  1. Comprehensive Characterization of Mesenchymal Stem Cells from Human Placenta and Fetal Membrane and Their Response to Osteoactivin Stimulation

    Directory of Open Access Journals (Sweden)

    C. M. Raynaud

    2012-01-01

    Full Text Available Mesenchymal stem cells (MSCs are the most promising seed cells for cell therapy and can be isolated from various sources of human adult tissues such as bone marrow (BM-MSC and adipose tissue. However, cells from these tissues must be obtained through invasive procedures. We, therefore, characterized MSCs isolated from fresh placenta (Pl-MSC and fetal membrane (Mb-MSC through morphological and fluorescent-activated cell sorting (FACS. MSC frequency is higher in membrane than placenta (2.14%  ± 0.65 versus 15.67%  ± 0.29%. Pl/Mb-MSCs in vitro expansion potential was significantly higher than BM-MSCs. We demonstrated that one of the MSC-specific marker is sufficient for MSC isolation and that culture in specific media is the optimal way for selecting very homogenous MSC population. These MSCs could be differentiated into mesodermal cells expressing cell markers and cytologic staining consistent with mature osteoblasts and adipocytes. Transcriptomic analysis and cytokine arrays demonstrated broad similarity between placenta- and membrane-derived MSCs and only discrete differences with BM-MSCs with enrichment of networks involved in bone differentiation. Pl/Mb-MSCs displayed higher osteogenic differentiation potential than BM-MSC when their response to osteoactivin was evaluated. Fetal-tissue-derived mesenchymal cells may, therefore, be considered as a major source of MSCs to reach clinical scale banking in particular for bone regeneration.

  2. Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda;

    2011-01-01

    Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxic...

  3. Serial in vivo imaging of the porcine heart after percutaneous, intramyocardially injected 111In-labeled human mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Lyngbaek, Stig; Ripa, Rasmus S; Haack-Sørensen, Mandana;

    2010-01-01

    This pilot trial aimed to investigate the utilization of (111)In-labeling of mesenchymal stromal cells (MSC) for in vivo tracking after intramyocardial transplantation in a xenotransplantation model with gender mismatched cells. Human male MSC were expanded ex vivo and labeled with (111)In...

  4. Serial in vivo imaging of the porcine heart after percutaneous, intramyocardially injected (111)In-labeled human mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Lyngbæk, Stig; Ripa, Rasmus Sejersten; Haack-Sørensen, Mandana;

    2009-01-01

    This pilot trial aimed to investigate the utilization of (111)In-labeling of mesenchymal stromal cells (MSC) for in vivo tracking after intramyocardial transplantation in a xenotransplantation model with gender mismatched cells. Human male MSC were expanded ex vivo and labeled with (111)In...

  5. Software Realization on the MSC nanoRISC Hardware Platform, for Communication according to the IEC61850 Standard

    Directory of Open Access Journals (Sweden)

    A. V. Kabović

    2015-06-01

    Full Text Available This paper describes software realization and its implementation for the communication, according to the IEC61850 standard, between the module for monitoring teleprotection devices and the control/monitoring server in a power substation. Teleprotection devices have an important role in the transmission of messages for power line section tripping. The software is implemented on the “MSC nanoRISC-S3C2416 MB2” hardware platform type, which belongs to the COM (computer on module systems.

  6. Instant stem cell therapy: Characterization and concentration of human mesenchymal stem cells in vitro

    Directory of Open Access Journals (Sweden)

    P Kasten

    2008-10-01

    Full Text Available In regenerative medicine, there is an approach to avoid expansion of the mesenchymal stem cell (MSC before implantation. The aim of this study was to compare methods for instant MSC therapy by use of a portable, automatic and closed system centrifuge that allows for the concentration of MSCs. The main outcome measures were the amount of MSCs per millilitre of bone marrow (BM, clusters of differentiation (CD, proliferation and differentiation capacities of the MSC. A volume reduction protocol was compared to the traditional laboratory methods of isolation using a Ficoll gradient and native BM. Fifty millilitres of BM were obtained from haematologically healthy male Caucasians (n=10, age 8 to 49 years. The number of colony forming units-fibroblast (CFU-F/ml BM was highest in the centrifuge volume reduction protocol, followed by the native BM (not significant, the centrifuge Ficoll (p=0.042 and the manual Ficoll procedure (p=0.001. The MSC of all groups could differentiate into the mesenchymal lineages without significant differences between the groups. The CD pattern was identical for all groups: CD13+; CD 44+; CD73 +; CD90+; CD105+; HLA-A,B,C+; CD14-; CD34-; CD45-; CD271-; HLA-DR-. In a further clinical pilot study (n=5 with 297 ml BM (SD 18.6, the volume reduction protocol concentrated the MSC by a factor of 14: there were 1.08 x 102 MSC/ml BM (standard deviation (SD 1.02 x 102 before concentration, 14.8 x 102 MSC/ ml BM (SD 12.4 x 102 after concentration, and on average 296 x 102 MSC (SD 248.9 x 102, range 86.4-691.5 x 102 were available for MSC therapy. The volume reduction protocol of the closed centrifuge allows for the highest concentration of the MSC, and therefore, is a promising candidate for instant stem cell therapy.

  7. Black hole evaporation: a paradigm

    International Nuclear Information System (INIS)

    A paradigm describing black hole evaporation in non-perturbative quantum gravity is developed by combining two sets of detailed results: (i) resolution of the Schwarzschild singularity using quantum geometry methods and (ii) time evolution of black holes in the trapping and dynamical horizon frameworks. Quantum geometry effects introduce a major modification in the traditional spacetime diagram of black hole evaporation, providing a possible mechanism for recovery of information that is classically lost in the process of black hole formation. The paradigm is developed directly in the Lorentzian regime and necessary conditions for its viability are discussed. If these conditions are met, much of the tension between expectations based on spacetime geometry and structure of quantum theory would be resolved

  8. Understanding the land management paradigm

    DEFF Research Database (Denmark)

    Enemark, Stig

    2006-01-01

    There is a worldwide need to build understanding of the land management paradigm and for institutional development to establish sustainable national concepts. This includes creation and adoption of a policy on land development, and an approach that combines the land administration/cadastre/land r......There is a worldwide need to build understanding of the land management paradigm and for institutional development to establish sustainable national concepts. This includes creation and adoption of a policy on land development, and an approach that combines the land administration....../cadastre/land registration function with topographic mapping. The author seeks to awaken more awareness of global trends in this area, recognising that the systems design involved is always unique....

  9. Human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Zaher, Walid; Al-Nbaheen, May;

    2012-01-01

    Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self......-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number...

  10. Tumorigenic heterogeneity in cancer stem cells evolved from long-term cultures of telomerase-immortalized human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Burns, Jorge S; Abdallah, Basem M; Guldberg, Per;

    2005-01-01

    Long-term cultures of telomerase-transduced adult human mesenchymal stem cells (hMSC) may evolve spontaneous genetic changes leading to tumorigenicity in immunodeficient mice (e.g., hMSC-TERT20). We wished to clarify whether this unusual phenotype reflected a rare but dominant subpopulation...... or if the stem cell origin allowed most cells to behave as cancer stem cells. Cultures of the hMSC-TERT20 strain at population doubling 440 were highly clonogenic (94%). From 110 single-cell clones expanded by 20 population doublings, 6 underwent detailed comparison. Like the parental population, each clone had...... tumorigenicity correlated with good viability plus capillary morphogenesis on serum starvation and high cyclin D1 expression. Thus, hMSC-TERT20 clones represent cancer stem cells with hierarchical tumorigenicity, providing new models to explore the stem cell hypothesis for cancer....

  11. Crises and paradigms in macroeconomics

    OpenAIRE

    Malcolm Sawyer

    2010-01-01

    Contrasts are drawn between mainstream macroeconomics (with the 'New Consensus in Macroeconomics' taken as the current manifestation) and heterodox macroeconomics and their abilities to comprehend the financial crises and world wide recession of 2007 – 09 for macroeconomic paradigms is discussed. Specifically, the contrasting ways in which the two schools of thought treat unemployment, human behaviour, aggregate and money and credit are discussed. It is concluded that the events of 2007 –...

  12. Membrane Paradigm and Holographic Hydrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Eling, Christopher [SISSA, Via Bonomea 265, 34136 Trieste, Italy and INFN Sezione di Trieste, Via Valerio 2, 34127 Trieste (Italy); Neiman, Yasha; Oz, Yaron, E-mail: cteling@sissa.it, E-mail: yashula@gmail.com, E-mail: yaronoz@post.tau.ac.il [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv 69978 (Israel)

    2011-09-22

    We discuss recent work showing that in certain cases the membrane paradigm equations governing the dynamics of black hole horizons can be recast as relativistic conservation law equations. In the context of gauge/gravity dualities, these equations are interpreted as defining the viscous hydrodynamics of a holographically dual relativistic field theory. Using this approach, one can derive the viscous transport coefficients and the form of the entropy current for field theories dual to gravity plus matter fields.

  13. Emergent Gravity Paradigm: Recent Progress

    CERN Document Server

    Padmanabhan, T

    2014-01-01

    Research during the last one decade or so suggests that the gravitational field equations in a large class of theories (including, but not limited to, general relativity) have the same status as the equations of, say, gas dynamics or elasticity. This paradigm provides a refreshingly different way of interpreting spacetime dynamics and highlights the fact that several features of classical gravitational theories have direct thermodynamic interpretation. I review the recent progress in this approach, achieved during the last few years.

  14. Employee discipline: a changing paradigm.

    Science.gov (United States)

    Raper, J L; Myaya, S N

    1993-12-01

    To increase the receptiveness of health care supervisors to a broader meaning of discipline and to simulate investigation of nontraditional methods of encouragement to employees who fail to meet minimum standards of conduct and thereby negatively affect the quality of patient care, a subjectively realistic view of the implications of the traditional punitive disciplinary paradigm is presented. Through the use of a case study, the authors present, explain, and apply the contemporary concept of discipline without punishment as first described by J. Huberman.

  15. Political Market. Paradigms and Realities

    Directory of Open Access Journals (Sweden)

    Vasile Macoviciuc

    2012-06-01

    Full Text Available The paper Political Market. Paradigms and Realities, by Simona Busoi, is an important contribution and a spadework within our specialized literature. Recently issued by Editura ASE (The Bucharest Academy of Economic Studies Publishing House, in the collection “Et in Arcadia ego”, it offers to the readers a synthesis of the literature destined to the study of political phenomena from an economic point of view, but also a lucid analysis of the Romanian political market.

  16. The Afrocentric Paradigm: Contours and Definitions.

    Science.gov (United States)

    Mazama, Ama

    2001-01-01

    Defines and describes Afrocentricity, suggesting that Afrocentricity within the academic context is best understood as a paradigm. Explains how Afrocentricity meets the definition of a paradigm, examining the affective, cognitive, and conative aspects of the Afrocentric paradigm (metaphysical and sociological) and looking at the structural and…

  17. Towards reduction of Paradigm coordination models

    NARCIS (Netherlands)

    Andova, S.; Groenewegen, L.P.J.; Vink, E.P. de; Aceto, L.; Mousavi, M.R.

    2011-01-01

    The coordination modelling language Paradigm addresses collaboration between components in terms of dynamic constraints. Within a Paradigm model, component dynamics are consistently specified at a detailed and a global level of abstraction. To enable automated verification of Paradigm models, a tran

  18. Long Period Variables: questioning the pulsation paradigm

    CERN Document Server

    Berlioz-Arthaud, Paul

    2016-01-01

    Long period variables, among them Miras, are thought to be pulsating. Under this approach the whole star inflates and deflates along a period that can vary from 100 to 900 days; that pulsation is assumed to produce shock waves on the outer layers of the star that propagate into the atmosphere and could account for the increase in luminosity and the presence of emission lines in the spectra of these stars. However, this paradigm can seriously be questioned from a theoretical point of view. First, in order to maintain a radial pulsation, the spherical symmetry of the star must be preserved: how can it be reconciled with the large convective cells present in these stars? or when close companions are detected? Secondly, how different radial and non-radial pulsation modes of a sphere could be all damped except one radial mode? These problems have no solution and significantly weigh on the pulsation paradigm. Acknowledging this inconsistency, we show that a close companion around these stars could account for the s...

  19. Orphism as a scientific paradigm

    Directory of Open Access Journals (Sweden)

    Biernat Przemyslaw

    2012-01-01

    Full Text Available In my essay I would like to examine current interpretative paradigm, which western scholarship cast on heterogenous and ambiguous data first to create and then to modify the notion of ‘orphism’. In case of paradigms preceding the actual one, the role which ‘orphism’ played in contemporary theories and controversies centered around the question of its significance for emergence of Christianity is well known. That is why in my work I would like to focus on deconstruction of interpretative consensus, elaborated in recent years, which is to be found in such works as Martin West’s The Orphic Poems (1983, Ritual Texts for the Afterlife. Orpheus and the Bacchic Gold Tablets by Fritz Graf and Sarah Iles-Johnston (2007 or monumental Orfeo y la tradición órfica. Un reencuentro (2008 edited by Alberto Bernabé. What is significant, inasmuch as we can write the history of Athenian religion or the history of Hellenistic kings’ worship, we still cannot write the history of orphism. In formulation of all these scholars it is an ahistorical phenomenon, a hidden constant in the sphere of Greek religion, never expressed directly and entirely, but always alluded to y ancient authors. I find difficult to agree with such a statement. The aim of my inquiry is to reveal assumptions of current paradigm, which are hidden in it, but leave a distinct impression on data.

  20. Poverty eradication: a new paradigm.

    Science.gov (United States)

    Pethe, V P

    1998-08-01

    This article offers a new paradigm for eradicating poverty in India. It was assumed incorrectly by Mahatma Gandhi that a good society without mass poverty would follow after independence. India copied Western models of development and developed giant factories, big dams, and megacities. Agriculture did not expand the number of jobs for people. The Western paradigm failed in India because of the false assumption of "trickle down" of income to the masses. The targeted programs to the poor did not directly benefit enough of the poor. Mega-industrialization led to reduced employment and higher skill needs. The model failed mainly because it was a proxy and relied on indirect ways of reaching the poor. The models failed to be adapted to conditions in India. The Swadeshi paradigm is a direct model for addressing mass poverty. Poverty is affected by immediate, intermediate, and ultimate determinants. Poverty begets social and economic problems, such as ignorance, ill health, high fertility, unemployment, and crime. In India and developing countries, mass poverty results from under use of human resources; lack of equal opportunities; and an outdated non-egalitarian social structure, an unjust global economic order, human cruelty, and erosion of ethical values. Indians are squandering their precious resources mimicking Western consumerism. Poverty leads to rapid population growth. People become productive assets with universal literacy, compulsory and free education, health services and sanitation, vocational training, and work ethics. India needs people-oriented policies with less emphasis on capital accumulation. PMID:12294462

  1. Poverty eradication: a new paradigm.

    Science.gov (United States)

    Pethe, V P

    1998-08-01

    This article offers a new paradigm for eradicating poverty in India. It was assumed incorrectly by Mahatma Gandhi that a good society without mass poverty would follow after independence. India copied Western models of development and developed giant factories, big dams, and megacities. Agriculture did not expand the number of jobs for people. The Western paradigm failed in India because of the false assumption of "trickle down" of income to the masses. The targeted programs to the poor did not directly benefit enough of the poor. Mega-industrialization led to reduced employment and higher skill needs. The model failed mainly because it was a proxy and relied on indirect ways of reaching the poor. The models failed to be adapted to conditions in India. The Swadeshi paradigm is a direct model for addressing mass poverty. Poverty is affected by immediate, intermediate, and ultimate determinants. Poverty begets social and economic problems, such as ignorance, ill health, high fertility, unemployment, and crime. In India and developing countries, mass poverty results from under use of human resources; lack of equal opportunities; and an outdated non-egalitarian social structure, an unjust global economic order, human cruelty, and erosion of ethical values. Indians are squandering their precious resources mimicking Western consumerism. Poverty leads to rapid population growth. People become productive assets with universal literacy, compulsory and free education, health services and sanitation, vocational training, and work ethics. India needs people-oriented policies with less emphasis on capital accumulation.

  2. Human bone-marrow-derived mesenchymal stem cells

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment...... of a variety of clinical conditions. The aim of this review is to provide an update regarding the biology of MSC, their identification and culture, and mechanisms controlling their proliferation and differentiation. We also review the current status of their clinical use. Areas in which research is needed...

  3. Mesenchymal stem cell therapy and lung diseases.

    Science.gov (United States)

    Akram, Khondoker M; Samad, Sohel; Spiteri, Monica; Forsyth, Nicholas R

    2013-01-01

    Mesenchymal stem cells (MSCs), a distinct population of adult stem cells, have amassed significant interest from both medical and scientific communities. An inherent multipotent differentiation potential offers a cell therapy option for various diseases, including those of the musculoskeletal, neuronal, cardiovascular and pulmonary systems. MSCs also secrete an array of paracrine factors implicated in the mitigation of pathological conditions through anti-inflammatory, anti-apoptotic and immunomodulatory mechanisms. The safety and efficacy of MSCs in human application have been confirmed through small- and large-scale clinical trials. However, achieving the optimal clinical benefit from MSC-mediated regenerative therapy approaches is entirely dependent upon adequate understanding of their healing/regeneration mechanisms and selection of appropriate clinical conditions. MSC-mediated acute alveolar injury repair. A cartoon depiction of an injured alveolus with associated inflammation and AEC apoptosis. Proposed routes of MSC delivery into injured alveoli could be by either intratracheal or intravenous routes, for instance. Following delivery a proposed mechanism of MSC action is to inhibit/reduce alveolar inflammation by abrogation of IL-1_-depenedent Tlymphocyte proliferation and suppression of TNF-_ secretion via macrophage activation following on from stimulation by MSC-secreted IL-1 receptor antagonist (IL-1RN). The inflammatory environment also stimulates MSC to secrete prostaglandin-E2 (PGE2) which can stimulate activated macrophages to secrete the anti-inflammatory cytokine IL-10. Inhibition of AEC apoptosis following injury can also be promoted via MSC stimulated up-regulation of the anti-apoptotic Bcl-2 gene. MSC-secreted KGF can stimulate AECII proliferation and migration propagating alveolar epithelial restitution. Alveolar structural engraftment of MSC is a rare event. PMID:22772131

  4. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

    Directory of Open Access Journals (Sweden)

    Ninna Aggerholm-Pedersen

    2016-01-01

    Full Text Available Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin.

  5. Mesenchymal stem cells for therapeutic purposes.

    Science.gov (United States)

    Sensebé, Luc; Bourin, Philippe

    2009-05-15

    Mesenchymal stem cells (MSC) are multipotent adult stem cells harboring a wide range of differentiations and non-human leukocyte antigen-restricted immunosuppressive properties that lead to an increasing use of MSC in immunomodulation and in regenerative medicine. To produce MSC, definitive standards are still lacking. Whatever the starting material used (e.g., bone marrow, adipose tissue, or cord blood), numerous parameters including cell plating density, number of passages, and culture medium, play a major role in the culture process and have to be determined. To date, the different production processes have been effective, and based on phenotypic analysis and differentiation potential, a first set of simple controls have been defined. However, controls of the final product should provide precise data on efficacy and safety. The next challenge will be to develop production processes that reach good manufacturing practices goals and to define more accurate control methods of cultivated MSC.

  6. Mesenchymal Stem Cell Attenuates Neutrophil-predominant Inflammation and Acute Lung Injury in an In Vivo Rat Model of Ventilator-induced Lung Injury

    OpenAIRE

    Tian-Shun Lai; Zhi-Hong Wang; Shao-Xi Cai

    2015-01-01

    Background: Subsequent neutrophil (polymorphonuclear neutrophil [PMN])-predominant inflammatory response is a predominant feature of ventilator-induced lung injury (VILI), and mesenchymal stem cell (MSC) can improve mice survival model of endotoxin-induced acute lung injury, reduce lung impairs, and enhance the repair of VILI. However, whether MSC could attenuate PMN-predominant inflammatory in the VILI is still unknown. This study aimed to test whether MSC intervention could attenuate the PM...

  7. Protocols for in vitro Differentiation of Human Mesenchymal Stem Cells into Osteogenic, Chondrogenic and Adipogenic Lineages.

    Science.gov (United States)

    Ciuffreda, Maria Chiara; Malpasso, Giuseppe; Musarò, Paola; Turco, Valentina; Gnecchi, Massimiliano

    2016-01-01

    Mesenchymal stem cells (MSC) possess high plasticity and the potential to differentiate into several different cell types; this characteristic has implications for cell therapy and reparative biotechnologies. MSC have been originally isolated from the bone marrow (BM-MSC), but they have been found also in other tissues such as adipose tissue, cord blood, synovium, skeletal muscle, and lung. MSC are able to differentiate in vitro and in vivo into several cell types such as bone, osteocytes, chondrocytes, adipocytes, and skeletal myocytes, just to name a few.During the last two decades, an increasing number of studies have proven the therapeutic potential of MSC for the treatment of neurodegenerative diseases, spinal cord and brain injuries, cardiovascular diseases, diabetes mellitus, and diseases of the skeleton. Their immuno-privileged profile allows both autologous and allogeneic use. For all these reasons, the scientific appeal of MSC is constantly on the rise.The identity of MSC is currently based on three main criteria: plastic-adherence capacity, defined epitope profile, and capacity to differentiate in vitro into osteocytes, chondrocytes, and adipocytes. Here, we describe standard protocols for the differentiation of BM-MSC into the osteogenic, chondrogenic, and adipogenic lineages. PMID:27236670

  8. Intranasal mesenchymal stem cell treatment for neonatal brain damage : long-term cognitive and sensorimotor improvement

    NARCIS (Netherlands)

    Donega, Vanessa; van Velthoven, Cindy T J; Nijboer, Cora H; van Bel, Frank; Kas, Martien J H; Kavelaars, Annemieke; Heijnen, Cobi J

    2013-01-01

    Mesenchymal stem cell (MSC) administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI) brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic wi

  9. Persistent circulating human insulin in sheep transplanted in utero with human mesenchymal stem cells

    Science.gov (United States)

    Ersek, Adel; Pixley, John S.; Goodrich, A. Daisy; Porada, Christopher D.; Almeida-Porada, Graca; Thain, David S.; Zanjani, Esmail D.

    2010-01-01

    Objective To determine if mesenchymal stem cells (MSC) derived from human fetal pancreatic tissue (pMSC) would engraft and differentiate in sheep pancreas following transplantation in utero. Methods A three-step culture system was established for generating human fetal pMSC. Sheep fetuses were transplanted during the fetal transplant receptivity period with human pMSC and evaluated for in situ and functional engraftment in their pancreas, liver and bone marrow. Results Isolation and expansion of adherent cells from the human fetal pancreas yielded a cell population with morphologic and phenotypic characteristics similar to MSC derived from bone marrow. This putative stem cell population could undergo multilineage differentiation in vitro. Three to 27 months after fetal transplantation, the pancreatic engraftment frequency (chimeric index) was 79% while functional engraftment was noted in 50% of transplanted sheep. Hepatic and marrow engraftment and expression was noted as well. Conclusion We have established a procedure for isolation of human fetal pMSC that display characteristics similar to bone marrow derived MSC. In vivo results suggest the pMSC engraft, differentiate and secrete human insulin from the sheep pancreas. PMID:20170708

  10. The effect of marrow mesenchymal stem cell transplantation on pulmonary fibrosis in rats

    Institute of Scientific and Technical Information of China (English)

    黄坤

    2012-01-01

    Objective To study the possible mechanisms of marrow mesenchymal stem cells(MSC) in therapy of bleomycin(BLM)-induced pulmonary fibrosis in rats. Methods Fifty-four female Wistar rats were randomly divided into a control group,a BLM group and a MSC group. The control group receivel intratracheal normal

  11. Differentiation of Mesenchymal Stem Cells under Hypoxia and Normoxia: Lipid Profiles Revealed by Time-of-Flight Secondary Ion Mass Spectrometry and Multivariate Analysis

    NARCIS (Netherlands)

    Georgi, N.; Cillero-Pastor, B.; Eijkel, G.B.; Chinnagounder Periyasamy, P.; Kiss, A.; Blitterswijk, van C.A.; Post, J.N.; Heeren, R.M.A.; Karperien, H.B.J.

    2015-01-01

    Mesenchymal stem cells (MSC) have the ability to self-renew and differentiate into multiple cell types valuable for clinical treatment of rheumatic pathologies. To study the chondrogenic potential of MSC and identify the conditions that recreate the native cartilage environment, we used time-of-flig

  12. Systemic mesenchymal stem cell administration enhances bone formation in fracture repair but not load-induced bone formation

    Directory of Open Access Journals (Sweden)

    AE Rapp

    2015-01-01

    Full Text Available Mesenchymal stem cells (MSC were shown to support bone regeneration, when they were locally transplanted into poorly healing fractures. The benefit of systemic MSC transplantation is currently less evident. There is consensus that systemically applied MSC are recruited to the site of injury, but it is debated whether they actually support bone formation. Furthermore, the question arises as to whether circulating MSC are recruited only in case of injury or whether they also participate in mechanically induced bone formation. To answer these questions we injected green fluorescent protein (GFP-labelled MSC into C57BL/6J mice, which were subjected either to a femur osteotomy or to non-invasive mechanical ulna loading to induce bone formation. We detected GFP-labelled MSC in the early (day 10 and late fracture callus (day 21 by immunohistochemistry. Stromal cell-derived factor 1 (SDF-1 or CXCL-12, a key chemokine for stem cell attraction, was strongly expressed by virtually all cells near the osteotomy – indicating that SDF-1 may mediate cell migration to the site of injury. We found no differences in SDF-1 expression between the groups. Micro-computed tomography (µCT revealed significantly more bone in the callus of the MSC treated mice compared to untreated controls. The bending stiffness of callus was not significantly altered after MSC-application. In contrast, we failed to detect GFP-labelled MSC in the ulna after non-invasive mechanical loading. Histomorphometry and µCT revealed a significant load-induced increase in bone formation; however, no further increase was found after MSC administration. Concluding, our results suggest that systemically administered MSC are recruited and support bone formation only in case of injury but not in mechanically induced bone formation.

  13. Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction.

    Science.gov (United States)

    Parashurama, Natesh; Ahn, Byeong-Cheol; Ziv, Keren; Ito, Ken; Paulmurugan, Ramasamy; Willmann, Jürgen K; Chung, Jaehoon; Ikeno, Fumiaki; Swanson, Julia C; Merk, Denis R; Lyons, Jennifer K; Yerushalmi, David; Teramoto, Tomohiko; Kosuge, Hisanori; Dao, Catherine N; Ray, Pritha; Patel, Manishkumar; Chang, Ya-Fang; Mahmoudi, Morteza; Cohen, Jeff Eric; Goldstone, Andrew Brooks; Habte, Frezghi; Bhaumik, Srabani; Yaghoubi, Shahriar; Robbins, Robert C; Dash, Rajesh; Yang, Phillip C; Brinton, Todd J; Yock, Paul G; McConnell, Michael V; Gambhir, Sanjiv S

    2016-09-01

    Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article. PMID:27308957

  14. International Politics: A Desirable Paradigm

    Institute of Scientific and Technical Information of China (English)

    Xia Aiding; Feng Shuai

    2007-01-01

    This article first traces the origin of four concepts: International Politics (IP), International Relations (IR), World Politics (WP) and Global Politics (GP) and discusses the similarities among these four paradigms. It then analyses their application both at home and abroad. Finally, it argues for the desirability of selecting the concept of IP in academic training, thus facilitating practical application of concepts. It asserts that this will not only enhance academic discussion about IP among different Chinese schools of thought, but also help blazing new ideas.

  15. New Indivisible Planetary Science Paradigm

    OpenAIRE

    Herndon, J. Marvin

    2013-01-01

    I present here a new, indivisible planetary science paradigm, a wholly self-consistent vision of the nature of matter in the Solar System, and dynamics and energy sources of planets. Massive-core planets formed by condensing and raining-out from within giant gaseous protoplanets at high pressures and high temperatures. Earth's complete condensation included a 300 Earth-mass gigantic gas/ice shell that compressed the rocky kernel to about 66% of Earth's present diameter. T-Tauri eruptions stri...

  16. Psychiatry beyond the current paradigm.

    LENUS (Irish Health Repository)

    Bracken, Pat

    2012-12-01

    A series of editorials in this Journal have argued that psychiatry is in the midst of a crisis. The various solutions proposed would all involve a strengthening of psychiatry\\'s identity as essentially \\'applied neuroscience\\'. Although not discounting the importance of the brain sciences and psychopharmacology, we argue that psychiatry needs to move beyond the dominance of the current, technological paradigm. This would be more in keeping with the evidence about how positive outcomes are achieved and could also serve to foster more meaningful collaboration with the growing service user movement.

  17. Mesenchymal Stem Cells Respond to Hypoxia by Increasing Diacylglycerols.

    Science.gov (United States)

    Lakatos, Kinga; Kalomoiris, Stefanos; Merkely, Béla; Nolta, Jan A; Fierro, Fernando A

    2016-02-01

    Mesenchymal stem cells (MSC) are currently being tested clinically for a plethora of conditions, with most approaches relying on the secretion of paracrine signals by MSC to modulate the immune system, promote wound healing, and induce angiogenesis. Hypoxia has been shown to affect MSC proliferation, differentiation, survival and secretory profile. Here, we investigate changes in the lipid composition of human bone marrow-derived MSC after exposure to hypoxia. Using mass spectrometry, we compared the lipid profiles of MSC derived from five different donors, cultured for two days in either normoxia (control) or hypoxia (1% oxygen). Hypoxia induced a significant increase of total triglycerides, fatty acids and diacylglycerols (DG). Remarkably, reduction of DG levels using the phosphatidylcholine-specific phospholipase C inhibitor D609 inhibited the secretion of VEGF and Angiopoietin-2, but increased the secretion of interleukin-8, without affecting significantly their respective mRNA levels. Functionally, incubation of MSC in hypoxia with D609 inhibited the potential of the cells to promote migration of human endothelial cells in a wound/scratch assay. Hence, we show that hypoxia induces in MSC an increase of DG that may affect the angiogenic potential of these cells. PMID:26212931

  18. Optimizing patient derived mesenchymal stem cells as virus carriers for a Phase I clinical trial in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Mader Emily K

    2013-01-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSC can serve as carriers to deliver oncolytic measles virus (MV to ovarian tumors. In preparation for a clinical trial to use MSC as MV carriers, we obtained cells from ovarian cancer patients and evaluated feasibility and safety of this approach. Methods MSC from adipose tissues of healthy donors (hMSC and nine ovarian cancer patients (ovMSC were characterized for susceptibility to virus infection and tumor homing abilities. Results Adipose tissue (range 0.16-3.96 grams from newly diagnosed and recurrent ovarian cancer patients yielded about 7.41×106 cells at passage 1 (range 4–9 days. Phenotype and doubling times of MSC were similar between ovarian patients and healthy controls. The time to harvest of 3.0×108 cells (clinical dose could be achieved by day 14 (range, 9–17 days. Two of nine samples tested had an abnormal karyotype represented by trisomy 20. Despite receiving up to 1.6×109 MSC/kg, no tumors were seen in SCID beige mice and MSC did not promote the growth of SKOV3 human ovarian cancer cells in mice. The ovMSC migrated towards primary ovarian cancer samples in chemotaxis assays and to ovarian tumors in athymic mice. Using non-invasive SPECT-CT imaging, we saw rapid co-localization, within 5–8 minutes of intraperitoneal administration of MV infected MSC to the ovarian tumors. Importantly, MSC can be pre-infected with MV, stored in liquid nitrogen and thawed on the day of infusion into mice without loss of activity. MV infected MSC, but not virus alone, significantly prolonged the survival of measles immune ovarian cancer bearing animals. Conclusions These studies confirmed the feasibility of using patient derived MSC as carriers for oncolytic MV therapy. We propose an approach where MSC from ovarian cancer patients will be expanded, frozen and validated to ensure compliance with the release criteria. On the treatment day, the cells will be thawed, washed, mixed with virus, briefly

  19. Good manufacturing practice-compliant animal-free expansion of human bone marrow derived mesenchymal stroma cells in a closed hollow-fiber-based bioreactor.

    Science.gov (United States)

    Nold, Philipp; Brendel, Cornelia; Neubauer, Andreas; Bein, Gregor; Hackstein, Holger

    2013-01-01

    Mesenchymal stroma cells (MSC) are increasingly recognized for various applications of cell-based therapies such as regenerative medicine or immunomodulatory treatment strategies. Standardized large-scale expansions of MSC under good manufacturing practice (GMP)-compliant conditions avoiding animal derived components are mandatory for further evaluation of these novel therapeutic approaches in clinical trials. We applied a novel automated hollow fiber cell expansion system (CES) for in vitro expansion of human bone marrow derived MSC employing a GMP-compliant culture medium with human platelet lysate (HPL). Between 8 and 32 ml primary bone marrow aspirate were loaded into the hollow fiber CES and cultured for 15-27 days. 2-58 million MSC were harvested after primary culture. Further GMP-compliant cultivation of second passage MSC for 13 days led to further 10-20-fold enrichment. Viability, surface antigen expression, differentiation capacity and immunosuppressive function of MSC cultured in the hollow fiber CES were in line with standard criteria for MSC definition. We conclude that MSC can be enriched from primary bone marrow aspirate in a GMP-conform manner within a closed hollow fiber bioreactor and maintain their T lymphocyte inhibitory capacity. Standardized and reliable conditions for large scale MSC expansion pave the way for safe applications in humans in different therapeutic approaches.

  20. Mesenchymal bone marrow cell therapy in a mouse model of chagas disease. Where do the cells go?

    Directory of Open Access Journals (Sweden)

    Jasmin

    Full Text Available BACKGROUND: Chagas disease, resulting from infection with the parasite Trypanosoma cruzi (T. cruzi, is a major cause of cardiomyopathy in Latin America. Drug therapy for acute and chronic disease is limited. Stem cell therapy with bone marrow mesenchymal cells (MSCs has emerged as a novel therapeutic option for cell death-related heart diseases, but efficacy of MSC has not been tested in Chagas disease. METHODS AND RESULTS: We now report the use of cell-tracking strategies with nanoparticle labeled MSC to investigate migration of transplanted MSC in a murine model of Chagas disease, and correlate MSC biodistribution with glucose metabolism and morphology of heart in chagasic mice by small animal positron emission tomography (microPET. Mice were infected intraperitoneally with trypomastigotes of the Brazil strain of T. cruzi and treated by tail vein injection with MSC one month after infection. MSCs were labeled with near infrared fluorescent nanoparticles and tracked by an in vivo imaging system (IVIS. Our IVIS results two days after transplant revealed that a small, but significant, number of cells migrated to chagasic hearts when compared with control animals, whereas the vast majority of labeled MSC migrated to liver, lungs and spleen. Additionally, the microPET technique demonstrated that therapy with MSC reduced right ventricular dilation, a phenotype of the chagasic mouse model. CONCLUSIONS: We conclude that the beneficial effects of MSC therapy in chagasic mice arise from an indirect action of the cells in the heart rather than a direct action due to incorporation of large numbers of transplanted MSC into working myocardium.

  1. Mesenchymal stem cell subpopulations: phenotype, property and therapeutic potential.

    Science.gov (United States)

    Mo, Miaohua; Wang, Shan; Zhou, Ying; Li, Hong; Wu, Yaojiong

    2016-09-01

    Mesenchymal stem cells (MSC) are capable of differentiating into cells of multiple cell lineages and have potent paracrine effects. Due to their easy preparation and low immunogenicity, MSC have emerged as an extremely promising therapeutic agent in regenerative medicine for diverse diseases. However, MSC are heterogeneous with respect to phenotype and function in current isolation and cultivation regimes, which often lead to incomparable experimental results. In addition, there may be specific stem cell subpopulations with definite differentiation capacity toward certain lineages in addition to stem cells with multi-differentiation potential. Recent studies have identified several subsets of MSC which exhibit distinct features and biological activities, and enhanced therapeutic potentials for certain diseases. In this review, we give an overview of these subsets for their phenotypic, biological and functional properties. PMID:27141940

  2. Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhao

    2015-01-01

    Full Text Available This study is aimed at investigating whether human umbilical cord mesenchymal stem cell- (hucMSC- derived exosomes (hucMSC-exosomes have a protective effect on acute myocardial infarction (AMI. Exosomes were characterized under transmission electron microscopy and the particles of exosomes were further examined through nanoparticle tracking analysis. Exosomes (400 μg protein were intravenously administrated immediately following ligation of the left anterior descending (LAD coronary artery in rats. Cardiac function was evaluated by echocardiography and apoptotic cells were counted using TUNEL staining. The cardiac fibrosis was assessed using Masson’s trichrome staining. The Ki67 positive cells in ischemic myocardium were determined using immunohistochemistry. The effect of hucMSC-exosomes on blood vessel formation was evaluated through tube formation and migration of human umbilical vein endothelial cells (EA.hy926 cells. The results indicated that ligation of the LAD coronary artery reduced cardiac function and induced cardiomyocyte apoptosis. Administration of hucMSC-exosomes significantly improved cardiac systolic function and reduced cardiac fibrosis. Moreover, hucMSC-exosomes protected myocardial cells from apoptosis and promoted the tube formation and migration of EA.hy926 cells. It is concluded that hucMSC-exosomes improved cardiac systolic function by protecting myocardial cells from apoptosis and promoting angiogenesis. These effects of hucMSC-exosomes might be associated with regulating the expression of Bcl-2 family.

  3. Patient-Specific Age: The Other Side of the Coin in Advanced Mesenchymal Stem Cell Therapy.

    Science.gov (United States)

    Schimke, Magdalena M; Marozin, Sabrina; Lepperdinger, Günter

    2015-01-01

    Multipotential mesenchymal stromal cells (MSC) are present as a rare subpopulation within any type of stroma in the body of higher animals. Prominently, MSC have been recognized to reside in perivascular locations, supposedly maintaining blood vessel integrity. During tissue damage and injury, MSC/pericytes become activated, evade from their perivascular niche and are thus assumed to support wound healing and tissue regeneration. In vitro MSC exhibit demonstrated capabilities to differentiate into a wide variety of tissue cell types. Hence, many MSC-based therapeutic approaches have been performed to address bone, cartilage, or heart regeneration. Furthermore, prominent studies showed efficacy of ex vivo expanded MSC to countervail graft-vs.-host-disease. Therefore, additional fields of application are presently conceived, in which MSC-based therapies potentially unfold beneficial effects, such as amelioration of non-healing conditions after tendon or spinal cord injury, as well as neuropathies. Working along these lines, MSC-based scientific research has been forged ahead to prominently occupy the clinical stage. Aging is to a great deal stochastic by nature bringing forth changes in an individual fashion. Yet, is aging of stem cells or/and their corresponding niche considered a determining factor for outcome and success of clinical therapies? PMID:26696897

  4. Patient-specific age: the other side of the coin in advanced mesenchymal stem cell therapy

    Directory of Open Access Journals (Sweden)

    Magdalena Maria Schimke

    2015-12-01

    Full Text Available Multipotential mesenchymal stromal cells (MSC are present as a rare subpopulation within any type of stroma in the body of higher animals. Prominently, MSC have been recognized to reside in perivascular locations, supposedly maintaining blood vessel integrity. During tissue damage and injury, MSC/pericytes become activated, evade from their perivascular niche and are thus assumed to support wound healing and tissue regeneration.In vitro MSC exhibit demonstrated capabilities to differentiate into a wide variety of tissue cell types. Hence, many MSC-based therapeutic approaches have been performed to address bone, cartilage or heart regeneration. Furthermore, prominent studies showed efficacy of ex vivo expanded MSC to countervail graft-versus-host-disease. Therefore, additional fields of application are presently conceived, in which MSC-based therapies potentially unfold beneficial effects, such as amelioration of non-healing conditions after tendon or spinal cord injury, as well as neuropathies. Working along these lines, MSC-based scientific research has been forged ahead to prominently occupy the clinical stage.Aging is to a great deal stochastic by nature bringing forth changes in an individual fashion. Yet, is aging of stem cells or/and their corresponding niche considered a determining factor for outcome and success of clinical therapies?

  5. Hypothesis Formation, Paradigms, and Openness

    Directory of Open Access Journals (Sweden)

    Conrad P. Pritscher

    2008-01-01

    Full Text Available A part of hypothesis formation, while necessary for scientific investigation, is beyond direct observation. Powerful hypothesis formation is more than logical and is facilitated by mind­opening. As Percy Bridgeman, Nobel laureate, said, science is: “Nothing more than doing one's damnedest with one's mind, no holds barred.” This paper suggests more open schooling helps generate more open hypothesizing which helps one do one's damnedest with one's mind. It is hypothesized that a more open process of hypothesis formation may help schools and society forge new ways of living and learning so that more people more often can do their damnedest with their mind. This writing does not offer a new paradigm but rather attempts to elaborate on the notion that new paradigms are difficult to form without openness to what was previously quasi­unthinkable. More on these topics and issues is included in the author's Reopening Einstein's Thought: About What Can't Be Learned From Textbooks ­­to be published by Sense Publishers in June 2008.

  6. Mesenchymal stem cells differentially modulate effector CD8+ T cell subsets and exacerbate experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Glenn, Justin D; Smith, Matthew D; Calabresi, Peter A; Whartenby, Katharine A

    2014-10-01

    Mesenchymal stem cells (MSC) have emerged as a promising candidate for inflammatory suppression and disease amelioration, especially of neuro-inflammatory diseases such as multiple sclerosis (MS). Auto-reactive CD4+ and CD8+ T cells acquire pathogenic IFNγ-producing- (Type I) and IL-17A-producing- (Type 17) effector phenotypes in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Although MSC have been extensively demonstrated to suppress pathogenic effector CD4+ T cells and CD4+ T cell-mediated EAE, surprisingly few studies have addressed their modulation of effector CD8+ T cells represented in MS or their impact on CD8+ T cell-mediated EAE. We find that MSC differentially modulate CD8+ T cell development depending on effector T cell subtype. MSC drive activated low-IFNγ producers toward an enhanced high-IFNγ Tc1-like phenotype but strongly inhibit the production of IL-17A and Tc17 polarization in vitro. These observations are underscored by differential MSC modulation of T cell activation, proliferation, and signature transcription factor up-regulation. In addition, effector CD8+ T cells co-cultured with MSC exhibited increased production of IL-2, a molecule known to enhance IFNγ, yet suppress IL-17A, production. Based on these in vitro effects on CD8+ T cells, we next evaluated their impact on the severity of EAE. To better evaluate CD8+ T cells, we immunized mice with MOG37-50 , which is a CD8-targeted epitope. Our results revealed a worsening of disease, consistent with their in vitro stimulation of Tc1 cells. These findings highlight the emerging duality of MSC in immune modulation and provide implications for their future use in immune-related diseases. PMID:24911892

  7. Input Files and Procedures for Analysis of SMA Hybrid Composite Beams in MSC.Nastran and ABAQUS

    Science.gov (United States)

    Turner, Travis L.; Patel, Hemant D.

    2005-01-01

    A thermoelastic constitutive model for shape memory alloys (SMAs) and SMA hybrid composites (SMAHCs) was recently implemented in the commercial codes MSC.Nastran and ABAQUS. The model is implemented and supported within the core of the commercial codes, so no user subroutines or external calculations are necessary. The model and resulting structural analysis has been previously demonstrated and experimentally verified for thermoelastic, vibration and acoustic, and structural shape control applications. The commercial implementations are described in related documents cited in the references, where various results are also shown that validate the commercial implementations relative to a research code. This paper is a companion to those documents in that it provides additional detail on the actual input files and solution procedures and serves as a repository for ASCII text versions of the input files necessary for duplication of the available results.

  8. Study on phenotypic and cytogenetic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    宋陆茜

    2013-01-01

    Objective To investigate phenotype,cell differentiation and cytogenetic properties of bone marrow(BM) mesenchymal stem cells(MSC)separated from the myelodysplastic syndrome(MDS) patients,and to analyze cytogenetic

  9. Biofabrication: a 21st century manufacturing paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Mironov, V; Trusk, T; Markwald, R [Medical University of South Carolina, Charleston, SC 29425 (United States); Kasyanov, V [Riga Stradins University, Riga (Latvia); Little, S [South Carolina EPSCoR/IDeA Program, Columbia, SC (United States); Swaja, R [South Carolina Bioengineering Alliance, Charleston, SC 29425 (United States)

    2009-06-01

    Biofabrication can be defined as the production of complex living and non-living biological products from raw materials such as living cells, molecules, extracellular matrices, and biomaterials. Cell and developmental biology, biomaterials science, and mechanical engineering are the main disciplines contributing to the emergence of biofabrication technology. The industrial potential of biofabrication technology is far beyond the traditional medically oriented tissue engineering and organ printing and, in the short term, it is essential for developing potentially highly predictive human cell- and tissue-based technologies for drug discovery, drug toxicity, environmental toxicology assays, and complex in vitro models of human development and diseases. In the long term, biofabrication can also contribute to the development of novel biotechnologies for sustainable energy production in the future biofuel industry and dramatically transform traditional animal-based agriculture by inventing 'animal-free' food, leather, and fur products. Thus, the broad spectrum of potential applications and rapidly growing arsenal of biofabrication methods strongly suggests that biofabrication can become a dominant technological platform and new paradigm for 21st century manufacturing. The main objectives of this review are defining biofabrication, outlining the most essential disciplines critical for emergence of this field, analysis of the evolving arsenal of biofabrication technologies and their potential practical applications, as well as a discussion of the common challenges being faced by biofabrication technologies, and the necessary conditions for the development of a global biofabrication research community and commercially successful biofabrication industry. (topical review)

  10. Biofabrication: a 21st century manufacturing paradigm.

    Science.gov (United States)

    Mironov, V; Trusk, T; Kasyanov, V; Little, S; Swaja, R; Markwald, R

    2009-06-01

    Biofabrication can be defined as the production of complex living and non-living biological products from raw materials such as living cells, molecules, extracellular matrices, and biomaterials. Cell and developmental biology, biomaterials science, and mechanical engineering are the main disciplines contributing to the emergence of biofabrication technology. The industrial potential of biofabrication technology is far beyond the traditional medically oriented tissue engineering and organ printing and, in the short term, it is essential for developing potentially highly predictive human cell- and tissue-based technologies for drug discovery, drug toxicity, environmental toxicology assays, and complex in vitro models of human development and diseases. In the long term, biofabrication can also contribute to the development of novel biotechnologies for sustainable energy production in the future biofuel industry and dramatically transform traditional animal-based agriculture by inventing 'animal-free' food, leather, and fur products. Thus, the broad spectrum of potential applications and rapidly growing arsenal of biofabrication methods strongly suggests that biofabrication can become a dominant technological platform and new paradigm for 21st century manufacturing. The main objectives of this review are defining biofabrication, outlining the most essential disciplines critical for emergence of this field, analysis of the evolving arsenal of biofabrication technologies and their potential practical applications, as well as a discussion of the common challenges being faced by biofabrication technologies, and the necessary conditions for the development of a global biofabrication research community and commercially successful biofabrication industry. PMID:20811099

  11. Dimensionality and spreading influence MSC YAP/TAZ signaling in hydrogel environments.

    Science.gov (United States)

    Caliari, Steven R; Vega, Sebastián L; Kwon, Michelle; Soulas, Elizabeth M; Burdick, Jason A

    2016-10-01

    Improved fundamental understanding of how cells interpret microenvironmental signals is integral to designing better biomaterial therapies. YAP/TAZ are key mediators of mechanosensitive signaling; however, it is not clear how they are regulated by the complex interplay of microenvironmental factors (e.g., stiffness and degradability) and culture dimensionality. Using covalently crosslinked norbornene-functionalized hyaluronic acid (HA) hydrogels with controlled stiffness (via crosslink density) and degradability (via susceptibility of crosslinks to proteolysis), we found that human mesenchymal stem cells (MSCs) displayed increased spreading and YAP/TAZ nuclear localization when cultured atop stiffer hydrogels; however, the opposite trend was observed when MSCs were encapsulated within degradable hydrogels. When stiffness-matched hydrogels of reduced degradability were used, YAP/TAZ nuclear translocation was greater in cells that were able to spread, which was confirmed through pharmacological inhibition of YAP/TAZ and actin polymerization. Together, these data illustrate that YAP/TAZ signaling is responsive to hydrogel stiffness and degradability, but the outcome is dependent on the dimensionality of cell-biomaterial interactions. PMID:27429252

  12. Characterization and Application of a Disposable Rotating Bed Bioreactor for Mesenchymal Stem Cell Expansion

    Directory of Open Access Journals (Sweden)

    Anne Neumann

    2014-11-01

    Full Text Available Recruitment of mesenchymal stromal cells (MSC into the field of tissue engineering is a promising development since these cells can be expanded vivo to clinically relevant numbers and, after expansion, retain their ability to differentiate into various cell lineages. Safety requirements and the necessity to obtain high cell numbers without frequent subcultivation of cells raised the question of the possibility of expanding MSC in one-way (single-use disposable bioreactors. In this study, umbilical cord-derived MSC (UC-MSC were expanded in a disposable Z 2000 H bioreactor under dynamic conditions. Z was characterized regarding residence time and mixing in order to evaluate the optimal bioreactor settings, enabling optimal mass transfer in the absence of shear stress, allowing an reproducible expansion of MSC, while maintaining their stemness properties. Culture of the UC-MSC in disposable Z 2000 H bioreactor resulted in a reproducible 8-fold increase of cell numbers after 5 days. Cells were shown to maintain specific MSC surface marker expression as well as trilineage differentiation potential and lack stress-induced premature senescence.

  13. ENVIRONMENTALISM AND CLASSIC PARADIGMS OF INTERNATIONAL RELATIONS

    OpenAIRE

    D. D. Miniaeva

    2014-01-01

    This article examines an environmentalism integration process into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism) into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism). The main purpose of this study is to reveal the result of this integration. Methods used in this article include analysis and comparison of "ecological" paradigms on selected parameters (the nature of international relations, actors, ta...

  14. Mesenchymal stem cells from rats with chronic kidney disease exhibit premature senescence and loss of regenerative potential.

    Directory of Open Access Journals (Sweden)

    Barbara Mara Klinkhammer

    Full Text Available Mesenchymal stem cell (MSC transplantation has the potential for organ repair. Nevertheless, some factors might lessen the regenerative potential of MSCs, e.g. donor age or systemic disease. It is thus important to carefully assess the patient's suitability for autologous MSC transplantation. Here we investigated the effects of chronic kidney disease (CKD on MSC function. We isolated bone marrow MSCs from remnant kidney rats (RK with CKD (CKD-RK-MSC and found signs of premature senescence: spontaneous adipogenesis, reduced proliferation capacity, active senescence-associated-β-galactosidase, accumulation of actin and a modulated secretion profile. The functionality of CKD-RK-MSCs in vivo was tested in rats with acute anti-Thy1.1-nephritis, where healthy MSCs have been shown to be beneficial. Rats received healthy MSCs, CKD-RK-MSC or medium by injection into the left renal artery. Kidneys receiving healthy MSCs exhibited accelerated healing of glomerular lesions, whereas CKD-RK-MSC or medium exerted no benefit. The negative influence of advanced CKD/uremia on MSCs was confirmed in a second model of CKD, adenine nephropathy (AD. MSCs from rats with adenine nephropathy (CKD-AD-MSC also exhibited cellular modifications and functional deficits in vivo. We conclude that CKD leads to a sustained loss of in vitro and in vivo functionality in MSCs, possibly due to premature cellular senescence. Considering autologous MSC therapy in human renal disease, studies identifying uremia-associated mechanisms that account for altered MSC function are urgently needed.

  15. Intramyocardial delivery of mesenchymal stem cell-seeded hydrogel preserves cardiac function and attenuates ventricular remodeling after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Eva Mathieu

    Full Text Available BACKGROUND: To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC hydrogel seeded with MSC (MSC+hydrogel could preserve cardiac function and attenuate left ventricular (LV remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDING: Si-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI. CONCLUSION/SIGNIFICANCE: These beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium.

  16. Human Serum is as Efficient as Fetal Bovine Serum in Supporting Proliferation and Differentiation of Human Multipotent Stromal (Mesenchymal) Stem Cells In Vitro and In Vivo

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Haack-Sørensen, Mandana; Al-Nbaheen, May;

    2011-01-01

    . FBS. hMSC-TERT or primary bone marrow derived hMSC induced to osteoblastic or adipocytic differentiation in the presence of HuS or FBS showed comparable levels of gene expression and protein production of osteoblastic markers (CBFA1/Runx2, alkaline phosphastase, collagen type I and osteocalcin...... pose a health risk for patients. METHODS: We carried out a side-by-side comparison of the effects of allogenic pooled human serum (HuS) versus FBS on hMSC proliferation and differentiation in vitro and in vivo. As a model for hMSC, we employed telomerase-immortalized hMSC; hMSC-TERT cell line. RESULTS...... subcutaneously in immune deficient mice. hMSC maintained in HuS vs. FBS formed comparable heterotopic bone. DISCUSSION: Human serum can support proliferation and differentiation of hMSC in vitro and can maintain their bone forming capacity in vivo. The use of human serum in cell cultures of hMSC intended...

  17. Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-an; LUO Rong-hua; ZHANG Xing; XIE Xiao-jie; HU Xin-yang; HE Ai-na; CHEN Jie; LI Jia-hui

    2006-01-01

    Objective: This study was performed to evaluate whether implantation of mesenchymal stem cell (MSC) would reduce left ventricular remodelling from the molecular mechanisms compared with angiotensin-converting enzyme inhibitors (ACEIs) perindopril into ischemic myocardium after acute myocardial infarction. Methods: Forty rats were divided into four groups: control, MSC, ACEI, MSC+ACEI groups. Bone marrow stem cell derived rat was injected immediately into a zone made ischemic by coronary artery ligation in MSC group and MSC+ACEI group. Phosphate-buffered saline (PBS) was injected into control group. Perindopril was administered p.o. to ACEI group and MSC+ACEI group. Six weeks after implantation, the rats were killed and heart sample was collected. Fibrillar collagen was observed by meliorative Masson's trichome stain. Western Blotting was employed to evaluate the protein expression of matrix metalloproteinase (MMP)-2, matrix metalloproteinase (MMP)-9 in infarction zone. The transcriptional level of MMP2, MMP9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1in infarction area was detected by reverse transcriptase PCR (RT-PCR) analysis. Results: The fibrillar collagen area, the protein expression of MMP2, MMP9 and the transcriptional level of MMP2, MMP9 mRNA in infarction zone reduced in MSC group,ACEI group, and MSC+ACEI group. No significant difference was detected in the expression of TIMP1 mRNA among the 4groups. Conclusion: Both MSC and ACEI could reduce infarction remodelling by altering collagen metabolism.

  18. Mineralized collagen scaffolds induce hMSC osteogenesis and matrix remodeling

    OpenAIRE

    Weisgerber, D.W.; Caliari, S.R.; Harley, B.A.C.

    2015-01-01

    Biomaterials for bone tissue engineering must be able to instruct cell behavior in the presence of the complex biophysical and biomolecular environments encountered in vivo. While soluble supplementation strategies have been identified to enhance osteogenesis, they are subject to significant diffusive loss in vivo or the need for frequent re-addition in vitro. This investigation therefore explored whether biophysical and biochemical properties of a mineralized collagen-GAG scaffold were suffi...

  19. Compressive Elasticity of Three-Dimensional Nanofiber Matrix Directs Mesenchymal Stem Cell Differentiation to Vascular Cells with Endothelial or Smooth Muscle Cell Markers

    OpenAIRE

    Wingate, Kathryn; Bonani, Walter; Tan, Yan; Bryant, Stephanie J.; Tan, Wei

    2012-01-01

    The importance of mesenchymal stem cell (MSC) in vascular regeneration is becoming increasingly recognized. However, few in vitro studies have been performed to identify the effects of environmental elasticity on the differentiation of MSC into vascular cell types. We utilized electrospinning and photopolymerization techniques to fabricate a 3D PEGdma nanofiber hydrogel matrix with a tunable elasticity for use as a cellular substrate. Compression testing demonstrated that the elastic modulus ...

  20. Understanding the land management paradigm

    DEFF Research Database (Denmark)

    Enemark, Stig

    2006-01-01

    Land management is the process by which the resources of land are put into good effect. Land management encompasses all activities associated with the management of land and natural resources that are required to achieve sustainable development. Land Administration Systems (LAS) are institutional...... development towards the capacity to design, build, and manage Land Administration Systems that incorporate sustainable land policies and efficient spatial data infrastructures.......Land management is the process by which the resources of land are put into good effect. Land management encompasses all activities associated with the management of land and natural resources that are required to achieve sustainable development. Land Administration Systems (LAS) are institutional...... frameworks complicated by the tasks they must perform, by national cultural, political and judicial settings, and by technology. This paper facilitates an overall understanding of the land management paradigm. This paper assists sharing LAS among countries with diverse legal systems and institutional...

  1. New Paradigms For Asteroid Formation

    CERN Document Server

    Johansen, Anders; Cuzzi, Jeffrey N; Morbidelli, Alessandro; Gounelle, Matthieu

    2015-01-01

    Asteroids and meteorites provide key evidence on the formation of planetesimals in the Solar System. Asteroids are traditionally thought to form in a bottom-up process by coagulation within a population of initially km-scale planetesimals. However, new models challenge this idea by demonstrating that asteroids of sizes from 100 to 1000 km can form directly from the gravitational collapse of small particles which have organised themselves in dense filaments and clusters in the turbulent gas. Particles concentrate passively between eddies down to the smallest scales of the turbulent gas flow and inside large-scale pressure bumps and vortices. The streaming instability causes particles to take an active role in the concentration, by piling up in dense filaments whose friction on the gas reduces the radial drift compared to that of isolated particles. In this chapter we review new paradigms for asteroid formation and compare critically against the observed properties of asteroids as well as constraints from meteo...

  2. Emerging Paradigms in Machine Learning

    CERN Document Server

    Jain, Lakhmi; Howlett, Robert

    2013-01-01

    This  book presents fundamental topics and algorithms that form the core of machine learning (ML) research, as well as emerging paradigms in intelligent system design. The  multidisciplinary nature of machine learning makes it a very fascinating and popular area for research.  The book is aiming at students, practitioners and researchers and captures the diversity and richness of the field of machine learning and intelligent systems.  Several chapters are devoted to computational learning models such as granular computing, rough sets and fuzzy sets An account of applications of well-known learning methods in biometrics, computational stylistics, multi-agent systems, spam classification including an extremely well-written survey on Bayesian networks shed light on the strengths and weaknesses of the methods. Practical studies yielding insight into challenging problems such as learning from incomplete and imbalanced data, pattern recognition of stochastic episodic events and on-line mining of non-stationary ...

  3. Datacubes as a Service Paradigm

    Science.gov (United States)

    Rossi, Angelo Pio; Baumann, Peter

    2016-04-01

    Spatio-temporal data sets often can be represented conveniently through datacubes as a common unifying paradigm. Flexible, scalable services can be offered based on the concept of a datacube query language while hiding the technicalities, thereby allowing user-friendly visual data interaction. One of today's most influential initiatives in Big Geo Data is EarthServer which is paving the way for flexible, scalable datacube services based on innovative NewSQL technology (Fig. 1). Researchers from Europe, the US and recently Australia have teamed up to rigorously materialize the datacube paradigm for Earth Observation, ocean, meteorological, and planetary science. EarthServer has established client and server technology for such spatio-temporal datacubes strictly based on the open datacube standards, OGC WCS and WPCS. The underlying scalable array engine, rasdaman, enables direct interaction, including 3-D visualization, what-if scenarios, common EO data processing, and general analytics on regular and irregular grids. Integration of datacube and metadata retrieval, together with advanced visualization based on NASA WorldWind, are geared towards an effective, user-friendly access and analysis. Conversely, EarthServer is significantly shaping the ISO, OGC, and INSPIRE Big Data standards landscape by being specification editor. Phase 1 of EarthServer has advanced scalable array data¬base technology into 100+ TB services; in phase 2, a federation of Petabyte datacubes is being built in Europe and Australia to perform ad-hoc querying and merging. Phase 1 reviewers have attested rasdaman to "significantly transform the way that scientists in different areas of Earth Science will be able to access and use data in a way that hitherto was not possible". Altogether, these large-scale deployments prove that datacubes are a convenient model for presenting users with a simple, consolidated view on the massive amount of data files gathered - "a cube tells more than a million

  4. CD146/MCAM defines functionality of human bone marrow stromal stem cell populations

    DEFF Research Database (Denmark)

    Harkness, Linda; Zaher, Walid; Ditzel, Nicholas;

    2016-01-01

    BACKGROUND: Identification of surface markers for prospective isolation of functionally homogenous populations of human skeletal (stromal, mesenchymal) stem cells (hMSCs) is highly relevant for cell therapy protocols. Thus, we examined the possible use of CD146 to subtype a heterogeneous h......MSC population. METHODS: Using flow cytometry and cell sorting, we isolated two distinct hMSC-CD146(+) and hMSC-CD146(-) cell populations from the telomerized human bone marrow-derived stromal cell line (hMSC-TERT). Cells were examined for differences in their size, shape and texture by using high......-content analysis and additionally for their ability to differentiate toward osteogenesis in vitro and form bone in vivo, and their migrational ability in vivo and in vitro was investigated. RESULTS: In vitro, the two cell populations exhibited similar growth rate and differentiation capacity to osteoblasts...

  5. Cardiac Migration of Endogenous Mesenchymal Stromal Cells in Patients with Inflammatory Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Caroline Schmidt-Lucke

    2015-01-01

    Full Text Available Introduction. Mesenchymal stromal cells (MSC have immunomodulatory features. The aim of this study was to investigate the migration and homing potential of endogenous circulating MSC in virus negative inflammatory cardiomyopathy (CMi. Methods. In 29 patients with n=23 or without n=6 CMi undergoing endomyocardial biopsies (EMB, transcardiac gradients (TCGs of circulating MSC were measured by flow cytometry from blood simultaneously sampled from aorta and coronary sinus. The presence of MSC in EMB, cardiac inflammation, and SDF-1α mRNA expression were detected via immunohistochemistry and real-time PCR. Results. MSC defined as CD45−CD34−CD11b−CD73+CD90+ cells accounted for 0.010 [0.0025–0.048]%/peripheral mononuclear cell (PMNC and as CD45−CD34−CD11b−CD73+CD105+ cells for 0.019 [0.0026–0.067]%/PMNC, both with similar counts in patients with or without cardiac inflammation. There was a 29.9% P<0.01 transcardiac reduction of circulating MSC in patients with CMi, correlating with the extent of cardiac inflammation (P<0.05, multivariate analysis. A strong correlation was found between the TCG of circulating MSC and numbers of MSC (CD45−CD34−CD90+CD105+ in EMB (r=-0.73, P<0.005. SDF-1α was the strongest predictor for increased MSC in EMB (P<0.005, multivariate analysis. Conclusions. Endogenous MSC continuously migrate to the heart in patients with CMi triggered by cardiac inflammation.

  6. Exosomes Secreted by Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Repair Critical-Sized Bone Defects through Enhanced Angiogenesis and Osteogenesis in Osteoporotic Rats

    Science.gov (United States)

    Qi, Xin; Zhang, Jieyuan; Yuan, Hong; Xu, Zhengliang; Li, Qing; Niu, Xin; Hu, Bin; Wang, Yang; Li, Xiaolin

    2016-01-01

    Bone defects caused by trauma, severe infection, tumor resection and skeletal abnormalities are common osteoporotic conditions and major challenges in orthopedic surgery, and there is still no effective solution to this problem. Consequently, new treatments are needed to develop regeneration procedures without side effects. Exosomes secreted by mesenchymal stem cells (MSCs) derived from human induced pluripotent stem cells (hiPSCs, hiPSC-MSC-Exos) incorporate the advantages of both MSCs and iPSCs with no immunogenicity. However, there are no reports on the application of hiPSC-MSC-Exos to enhance angiogenesis and osteogenesis under osteoporotic conditions. HiPSC-MSC-Exos were isolated and identified before use. The effect of hiPSC-MSC-Exos on the proliferation and osteogenic differentiation of bone marrow MSCs derived from ovariectomized (OVX) rats (rBMSCs-OVX) in vitro were investigated. In vivo, hiPSC-MSC-Exos were implanted into critical size bone defects in ovariectomized rats, and bone regeneration and angiogenesis were examined by microcomputed tomography (micro-CT), sequential fluorescent labeling analysis, microfil perfusion and histological and immunohistochemical analysis. The results in vitro showed that hiPSC-MSC-Exos enhanced cell proliferation and alkaline phosphatase (ALP) activity, and up-regulated mRNA and protein expression of osteoblast-related genes in rBMSCs-OVX. In vivo experiments revealed that hiPSC-MSC-Exos dramatically stimulated bone regeneration and angiogenesis in critical-sized calvarial defects in ovariectomized rats. The effect of hiPSC-MSC-Exos increased with increasing concentration. In this study, we showed that hiPSC-MSC-Exos effectively stimulate the proliferation and osteogenic differentiation of rBMSCs-OVX, with the effect increasing with increasing exosome concentration. Further analysis demonstrated that the application of hiPSC-MSC-Exos+β-TCP scaffolds promoted bone regeneration in critical-sized calvarial defects by

  7. Mechanisms of mesenchymal stem/stromal cell function.

    Science.gov (United States)

    Spees, Jeffrey L; Lee, Ryang Hwa; Gregory, Carl A

    2016-01-01

    The past decade has seen an explosion of research directed toward better understanding of the mechanisms of mesenchymal stem/stromal cell (MSC) function during rescue and repair of injured organs and tissues. In addition to delineating cell-cell signaling and molecular controls for MSC differentiation, the field has made particular progress in defining several other mechanisms through which administered MSCs can promote tissue rescue/repair. These include: 1) paracrine activity that involves secretion of proteins/peptides and hormones; 2) transfer of mitochondria by way of tunneling nanotubes or microvesicles; and 3) transfer of exosomes or microvesicles containing RNA and other molecules. Improved understanding of MSC function holds great promise for the application of cell therapy and also for the development of powerful cell-derived therapeutics for regenerative medicine. Focusing on these three mechanisms, we discuss MSC-mediated effects on immune cell responses, cell survival, and fibrosis and review recent progress with MSC-based or MSC-derived therapeutics. PMID:27581859

  8. Multi-Composite Bioactive Osteogenic Sponges Featuring Mesenchymal Stem Cells, Platelet-Rich Plasma, Nanoporous Silicon Enclosures, and Peptide Amphiphiles for Rapid Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Dongmei Fan

    2011-06-01

    Full Text Available A novel bioactive sponge was created with a composite of type I collagen sponges or porous poly(e-caprolactone (PCL scaffolds, platelet-rich plasma (PRP, BMP2-loaded nanoporous silicon enclosure (NSE microparticles, mineralizing peptide amphiphiles (PA, and mesenchymal stem cells (MSC. Primary MSC from cortical bone (CB  tissue proved to form more and larger colony units, as well as produce more mineral matrix under osteogenic differentiation, than MSC from bone marrow (BM. Coating pre-treatments were optimized for maximum cell adhesion and mineralization, while a PRP-based gel carrier was created to efficiently deliver and retain MSC and  microparticles within a porous scaffold while simultaneously promoting cell recruitment, proliferation, and angiogenesis. Components and composite sponges were evaluated for osteogenic differentiation in vitro. Osteogenic sponges were loaded with MSC, PRP, PA, and NSE and implanted subcutaneously in rats to evaluate the formation of bone tissue and angiogenesis in vivo. It was found that the combination of a collagen sponge with CB MSC, PRP, PA, and the BMP2-releasing NSE formed the most bone and was most vascularized by four weeks compared to analogous composites featuring BM MSC or PCL or lacking PRP, PA, and NSE. This study indicates that CB MSC should be considered as an alternative to marrow as a source of stem cells, while the PRP-PA cell and microparticle delivery system may be utilized for diverse tissue engineering applications.

  9. Stem cell therapy independent of stemness.

    Science.gov (United States)

    Lee, Techung

    2012-12-26

    Mesenchymal stem cell (MSC) therapy is entering a new era shifting the focus from initial feasibility study to optimization of therapeutic efficacy. However, how MSC therapy facilitates tissue regeneration remains incompletely characterized. Consistent with the emerging notion that secretion of multiple growth factors/cytokines (trophic factors) by MSC provides the underlying tissue regenerative mechanism, the recent study by Bai et al demonstrated a critical therapeutic role of MSC-derived hepatocyte growth factor (HGF) in two animal models of multiple sclerosis (MS), which is a progressive autoimmune disorder caused by damage to the myelin sheath and loss of oligodendrocytes. Although current MS therapies are directed toward attenuation of the immune response, robust repair of myelin sheath likely requires a regenerative approach focusing on long-term replacement of the lost oligodendrocytes. This approach appears feasible because adult organs contain various populations of multipotent resident stem/progenitor cells that may be activated by MSC trophic factors as demonstrated by Bai et al This commentary highlights and discusses the major findings of their studies, emphasizing the anti-inflammatory function and trophic cross-talk mechanisms mediated by HGF and other MSC-derived trophic factors in sustaining the treatment benefits. Identification of multiple functionally synergistic trophic factors, such as HGF and vascular endothelial growth factor, can eventually lead to the development of efficacious cell-free therapeutic regimens targeting a broad spectrum of degenerative conditions. PMID:23516128

  10. Polycaprolactone nanomesh cultured with hMSC evaluated by synchrotron tomography

    DEFF Research Database (Denmark)

    Nygaard, Jens Vinge; Andersen, Morten Østergaard; Cloetens, Peter;

    substrates while proliferating preferentially on the stiffer ones. This implicates that substrate rigidity is a critical design parameter in the development of scaffolds aimed at eliciting maximal cell and tissue function. From mechanics it is known that the stiffness of a porous structures scales...... network. These beams are called Plateau borders and are typically solid structures. Thus their stiffness depends solely on the stiffness of the selected biopolymer and the method of production. In this study we demonstrate that it is possible to control the porosity not only of the macroscopic porous...... scaffold but also of the Plateau borders constituting the scaffold.   Materials and Methods Polycaprolactone scaffolds were prepared by thermal induced phase separation followed by lyophilization. Processing conditions were chosen to range the relative density of the obtained scaffolds and its Plateau...

  11. Polycaprolactone nanomesh cultured with hMSC evaluated by synchrotron tomography

    DEFF Research Database (Denmark)

    Nygaard, Jens Vinge; Andersen, Morten Østergaard; Cloetens, Peter;

    2009-01-01

    substrates while proliferating preferentially on the stiffer ones. This implicates that substrate rigidity is a critical design parameter in the development of scaffolds aimed at eliciting maximal cell and tissue function. From mechanics it is known that the stiffness of a porous structures scales...... network. These beams are called Plateau borders and are typically solid structures. Thus their stiffness depends solely on the stiffness of the selected biopolymer and the method of production. In this study we demonstrate that it is possible to control the porosity not only of the macroscopic porous...... scaffold but also of the Plateau borders constituting the scaffold.   Materials and Methods Polycaprolactone scaffolds were prepared by thermal induced phase separation followed by lyophilization. Processing conditions were chosen to range the relative density of the obtained scaffolds and its Plateau...

  12. Is This the Paradigm Shift We Need?

    Science.gov (United States)

    Mirvis, Jonathan

    2012-01-01

    Dr. Woocher's essay, states Mirvis, is seminal in the field of Jewish education. It proposes a new paradigm for Jewish education in North America. This proposed paradigm is supported by a comprehensive multi-disciplinary research drawing on literature from education, philosophy, history, sociology, psychology, and economics. The essay reflects a…

  13. Towards a New Paradigm of Moral Personhood

    Science.gov (United States)

    Frimer, Jeremy A.; Walker, Lawrence J.

    2008-01-01

    Moral psychology is between paradigms. Kohlberg's model of moral rationality has proved inadequate in explaining action; yet its augmentation--moral personality--awaits empirical embodiment. This article addresses some critical issues in developing a comprehensive empirical paradigm of moral personhood. Is a first-person or a third-person…

  14. The cognitive paradigm and the immunological homunculus.

    Science.gov (United States)

    Cohen, I R

    1992-12-01

    In last month's issue of Immunology Today, Irun Cohen discussed the inadequacies of the clonal selection paradigm and proposed a cognitive paradigm in which preformed internal images guide and restrict the process of clonal activation. Here he clarifies the nature of these internal images, during on concrete examples from the image of infection and the image of self, the immunological homunculus.

  15. Programming Paradigms in Computer Science Education

    OpenAIRE

    Bolshakova, Elena

    2005-01-01

    Main styles, or paradigms of programming – imperative, functional, logic, and object-oriented – are shortly described and compared, and corresponding programming techniques are outlined. Programming languages are classified in accordance with the main style and techniques supported. It is argued that profound education in computer science should include learning base programming techniques of all main programming paradigms.

  16. Efficient generation of multipotent mesenchymal stem cells from umbilical cord blood in stroma-free liquid culture.

    Directory of Open Access Journals (Sweden)

    Rowayda Peters

    Full Text Available BACKGROUND: Haematopoiesis is sustained by haematopoietic (HSC and mesenchymal stem cells (MSC. HSC are the precursors for blood cells, whereas marrow, stroma, bone, cartilage, muscle and connective tissues derive from MSC. The generation of MSC from umbilical cord blood (UCB is possible, but with low and unpredictable success. Here we describe a novel, robust stroma-free dual cell culture system for long-term expansion of primitive UCB-derived MSC. METHODS AND FINDINGS: UCB-derived mononuclear cells (MNC or selected CD34(+ cells were grown in liquid culture in the presence of serum and cytokines. Out of 32 different culture conditions that have been tested for the efficient expansion of HSC, we identified one condition (DMEM, pooled human AB serum, Flt-3 ligand, SCF, MGDF and IL-6; further denoted as D7 which, besides supporting HSC expansion, successfully enabled long-term expansion of stromal/MSC from 8 out of 8 UCB units (5 MNC-derived and 3 CD34(+ selected cells. Expanded MSC displayed a fibroblast-like morphology, expressed several stromal/MSC-related antigens (CD105, CD73, CD29, CD44, CD133 and Nestin but were negative for haematopoietic cell markers (CD45, CD34 and CD14. MSC stemness phenotype and their differentiation capacity in vitro before and after high dilution were preserved throughout long-term culture. Even at passage 24 cells remained Nestin(+, CD133(+ and >95% were positive for CD105, CD73, CD29 and CD44 with the capacity to differentiate into mesodermal lineages. Similarly we show that UCB derived MSC express pluripotency stem cell markers despite differences in cell confluency and culture passages. Further, we generated MSC from peripheral blood (PB MNC of 8 healthy volunteers. In all cases, the resulting MSC expressed MSC-related antigens and showed the capacity to form CFU-F colonies. CONCLUSIONS: This novel stroma-free liquid culture overcomes the existing limitation in obtaining MSC from UCB and PB enabling so far unmet

  17. Macrophage interactions with polylactic acid and chitosan scaffolds lead to improved recruitment of human mesenchymal stem/stromal cells: a comprehensive study with different immune cells.

    Science.gov (United States)

    Caires, Hugo R; Esteves, Tiago; Quelhas, Pedro; Barbosa, Mário A; Navarro, Melba; Almeida, Catarina R

    2016-09-01

    Despite the importance of immune cell-biomaterial interactions for the regenerative outcome, few studies have investigated how distinct three-dimensional biomaterials modulate the immune cell-mediated mesenchymal stem/stromal cells (MSC) recruitment and function. Thus, this work compares the response of varied primary human immune cell populations triggered by different model scaffolds and describes its functional consequence on recruitment and motility of bone marrow MSC. It was found that polylactic acid (PLA) and chitosan scaffolds lead to an increase in the metabolic activity of macrophages but not of peripheral blood mononuclear cells (PBMC), natural killer (NK) cells or monocytes. PBMC and NK cells increase their cell number in PLA scaffolds and express a secretion profile that does not promote MSC recruitment. Importantly, chitosan increases IL-8, MIP-1, MCP-1 and RANTES secretion by macrophages while PLA stimulates IL-6, IL-8 and MCP-1 production, all chemokines that can lead to MSC recruitment. This secretion profile of macrophages in contact with biomaterials correlates with the highest MSC invasion. Furthermore, macrophages enhance stem cell motility within chitosan scaffolds by 44% but not in PLA scaffolds. Thus, macrophages are the cells that in contact with engineered biomaterials become activated to secrete bioactive molecules that stimulate MSC recruitment. PMID:27628173

  18. Macrophage interactions with polylactic acid and chitosan scaffolds lead to improved recruitment of human mesenchymal stem/stromal cells: a comprehensive study with different immune cells.

    Science.gov (United States)

    Caires, Hugo R; Esteves, Tiago; Quelhas, Pedro; Barbosa, Mário A; Navarro, Melba; Almeida, Catarina R

    2016-09-01

    Despite the importance of immune cell-biomaterial interactions for the regenerative outcome, few studies have investigated how distinct three-dimensional biomaterials modulate the immune cell-mediated mesenchymal stem/stromal cells (MSC) recruitment and function. Thus, this work compares the response of varied primary human immune cell populations triggered by different model scaffolds and describes its functional consequence on recruitment and motility of bone marrow MSC. It was found that polylactic acid (PLA) and chitosan scaffolds lead to an increase in the metabolic activity of macrophages but not of peripheral blood mononuclear cells (PBMC), natural killer (NK) cells or monocytes. PBMC and NK cells increase their cell number in PLA scaffolds and express a secretion profile that does not promote MSC recruitment. Importantly, chitosan increases IL-8, MIP-1, MCP-1 and RANTES secretion by macrophages while PLA stimulates IL-6, IL-8 and MCP-1 production, all chemokines that can lead to MSC recruitment. This secretion profile of macrophages in contact with biomaterials correlates with the highest MSC invasion. Furthermore, macrophages enhance stem cell motility within chitosan scaffolds by 44% but not in PLA scaffolds. Thus, macrophages are the cells that in contact with engineered biomaterials become activated to secrete bioactive molecules that stimulate MSC recruitment.

  19. An oblique membrane paradigm for cosmological horizon

    CERN Document Server

    Wang, Tower

    2014-01-01

    The membrane paradigm is a formalism for studying the event horizon of black holes. After analyzing it with some technical details and realizing it in the Reissner-Nordstrom black hole, we extend the paradigm to cosmological horizons. A standard membrane paradigm is established for the pure de Sitter horizon, and an oblique membrane paradigm is proposed for the trapping horizon of the Friedmann-Lemaitre-Robertson-Walker universe. In the latter case, the cosmological stretched horizon is oblique, thus the running of renormalization parameter is nonzero in the timelike direction and gives a correction to the membrane pressure. In this paradigm, the cosmological equations come from continuity equations of the membrane fluid and the bulk fluid respectively.

  20. The Immunomodulation Effect of UC-MSC on the Inflammatory Chemokines of Rats with Collagen Type Ⅱ Induced Arthritis%脐带间充质干细胞移植对胶原诱导型关节炎大鼠炎性趋化因子表达的影响

    Institute of Scientific and Technical Information of China (English)

    康丽莉; 于立耘; 倪军; 顾健; 林传明; 沈连军; 顾蔚; 孙幸; 闪丹

    2012-01-01

    目的 观察脐带间充质干细胞(umbilical cord mesenchymal stem cells,UC-MSC)移植对胶原诱导型关节炎(collagen typeⅡ-induced arthritis,CIA)大鼠模型血清中:血管细胞间黏附分子-1(VCAM-1)、基质细胞衍生因子-1(SDF-1)、内皮细胞生长因子(VEGF)、肿瘤坏死因子-α(TNF-α)表达水平的影响,初步探讨UC-MSC移植对CIA大鼠炎性趋化因子的调节作用.方法 采用鸡Ⅱ型胶原加完全弗氏佐剂建立CIA大鼠模型,经大鼠尾静脉注射UC-MSC;以酶联免疫吸附试验(ELISA)检测各组大鼠干预前后血清VCAM-1、SDF-1、VEGF、TNF-α水平变化.结果 模型组血清VCAM-1、SDF-1、VEGF、TNF-α水平均明显高于同期空白对照组(P<0.05);经UC-MSC治疗组上述炎症因子水平逐渐降低,至第5周上述指标均接近空白对照组(P<0.05).结论 CIA大鼠存在免疫功能紊乱,其炎症趋化因子水平显著增高;UC-MSC能下调CIA大鼠炎症趋化因子水平,减轻机体免疫性炎症反应,促进疾病缓解,改善预后.%Objective To observe the immunomodulation effects of umbilical cord mesenchymal stem cells (UC-MSC) on the VCAM-1, SDF-1, VEGF, TNF-α of rats with collagen Ⅱ induced arthritis ( CIA). Methods First, The rats were immunized by intradermal injection of chickencollagen type Ⅱ emulisified with complete Freund's adjuvant (CFA). The swelling of foot ,hair color ,and action state of the rats were observed after injecting UC-MSC by caudal vein,the rats were scored with the arthritis index( AI) once a week. Then,The CD 4,CD 25 of peripheral blood lymphocytes and the CD 11b of peripheral blood neutrophil were detected by flow cytometry(FCM) ;The concentration of IL-17 in serum was detected by ELISA. Results Obvious swelling of the feet were found in the experiment group compared with norma group. ELISA the concentration of VCAM-1 ,SDF-1, VEGF,TNF-α in serum of the experiment group are higher than normal group (P <0. 05). After UC-MSC treatment

  1. Liver-specific gene expression in mesenchymal stem cells is induced by liver cells

    Institute of Scientific and Technical Information of China (English)

    Claudia Lange; Philipp Bassler; Michael V. Lioznov; Helge Bruns; Dietrich Kluth; Axel R. Zander; Henning C. Fiegel

    2005-01-01

    AIM: The origin of putative liver cells from distinct bone marrow stem cells, e.g. hematopoietic stem cells or multipotent adult progenitor cells was found in recent in vitro studies. Cell culture experiments revealed a key role of growth factors for the induction of liver-specific genes in stem cell cultures. We investigated the potential of rat mesenchymal stem cells (MSC) from bone marrow to differentiate into hepatocytic cells in vitro. Furthermore,we assessed the influence of cocultured liver cells on induction of liver-specific gene expression.METHODS: Mesenchymal stem cells were marked with green fluorescent protein (GFP) by retroviral gene transduction. Clonal marked MSC were either cultured under liver stimulating conditions using fibronectin-coated culture dishes and medium supplemented with SCF, HGF,EGF, and FGF-4 alone, or in presence of freshly isolated rat liver cells. Cells in cocultures were harvested and GFP+ or GFP- cells were separated using fluorescence activated cell sorting. RT-PCR analysis for the stem cell marker Thy1 and the hepatocytic markers CK-18, albumin, CK-19,and AFP was performed in the different cell populations.RESULTS: Under the specified culture conditions, rat MSC cocultured with liver cells expressed albumin-, CK-18,CK-19, and AFP-RNA over 3 weeks, whereas MSC cultured alone did not show liver specific gene expression.CONCLUSION: The results indicate that (1) rat MSC from bone marrow can differentiate towards hepatocytic lineage in vitro, and (2) that the microenvironment plays a decisive role for the induction of hepatic differentiation of rMSC.

  2. The Physical and Cognitive Paradigms in Information Retrieval Research.

    Science.gov (United States)

    Ellis, David

    1992-01-01

    Explores the role of paradigms in information retrieval research and discusses the nature of a paradigm and the applicability of the paradigm concept to a multidisciplinary field such as information science. The features of the physical paradigm and the cognitive paradigm are outlined, and their origins, nature, and role are examined. (55…

  3. Local delivery of mesenchymal stem cells with poly-lactic-co-glycolic acid nano-fiber scaffold suppress arthritis in rats.

    Directory of Open Access Journals (Sweden)

    Xiangmei Zhang

    Full Text Available Mesenchymal stem cells (MSC have been used recently for the treatment of autoimmune diseases in murine animal models due to the immunoregulatory capacity. Current utilization of MSC requires cells in certain quantity with multiple courses of administration, leading to limitation in clinical usage. Here we efficiently treated collagen-induced arthritis rats with a single local implantation with reduced number of MSC (2∼20% of previous studies with nano-fiber poly-lactic-co-glycolic acid (nano-fiber scaffold. MSC seeded on nano-fiber scaffold suppressed arthritis and bone destruction due to inhibition of systemic inflammatory reaction and immune response by suppressing T cell proliferation and reducing anti- type II collagen antibody production. In vivo tracing of MSC demonstrated that these cells remained within the scaffold without migrating to other organs. Meanwhile, in vitro culture of MSC with nano-fiber scaffold significantly increased TGF-β1 production. These results indicate an efficient utilization of MSC with the scaffold for destructive joints in rheumatoid arthritis by a single and local inoculation. Thus, our data may serve as a new strategy for MSC-based therapy in inflammatory diseases and an alternative delivery method for bone destruction treatment.

  4. Human Cardiac Mesenchymal Stromal Cells with CD105+CD34- Phenotype Enhance the Function of Post-Infarction Heart in Mice

    Science.gov (United States)

    Wiśniewska, Ewa; Jarosz-Biej, Magdalena; Smolarczyk, Ryszard; Cichoń, Tomasz; Głowala-Kosińska, Magdalena; Śliwka, Joanna; Garbacz, Marcin; Szczypior, Mateusz; Jaźwiec, Tomasz; Langrzyk, Agnieszka; Zembala, Michał; Szala, Stanisław

    2016-01-01

    Aims The aim of the present study was to isolate mesenchymal stromal cells (MSC) with CD105+CD34- phenotype from human hearts, and to investigate their therapeutic potential in a mouse model of hindlimb ischemia and myocardial infarction (MI). The study aimed also to investigate the feasibility of xenogeneic MSCs implantation. Methods and Results MSC isolated from human hearts were multipotent cells. Separation of MSC with CD105+CD34- phenotype limited the heterogeneity of the originally isolated cell population. MSC secreted a number of anti-inflammatory and proangiogenic cytokines (mainly IL-6, IL-8, and GRO). Human MSC were transplanted into C57Bl/6NCrl mice. Using the mouse model of hindlimb ischemia it was shown that human MSC treated mice demonstrated a higher capillary density 14 days after injury. It was also presented that MSC administrated into the ischemic muscle facilitated fast wound healing (functional recovery by ischemic limb). MSC transplanted into an infarcted myocardium reduced the post-infarction scar, fibrosis, and increased the number of blood vessels both in the border area, and within the post-infarction scar. The improvement of left ventricular ejection fraction was also observed. Conclusion In two murine models (hindlimb ischemia and MI) we did not observe the xenotransplant rejection. Indeed, we have shown that human cardiac mesenchymal stromal cells with CD105+CD34- phenotype exhibit therapeutic potential. It seems that M2 macrophages are essential for healing and repair of the post-infarcted heart. PMID:27415778

  5. Medialogy (English Information Brochure on the education M.Sc.,Medialogy, 3rd to 10th semester (B.Sc. & M.Sc) - For graduates from higher study programmes such as Multimedia Design and IT Graduates)

    DEFF Research Database (Denmark)

    Nordahl, Rolf

    2005-01-01

    An information brochure, 24 pages, in English which describes the education M.Sc., Medialogy, offered by Aalborg University in Copenhagen and Esbjerg. The brochure describes the 3rd to 10th semester (B.Sc. and M.Sc. degree) of the education. The information is primarily directed toward potential...

  6. MDMA and the "ecstasy paradigm".

    Science.gov (United States)

    Cole, Jon C

    2014-01-01

    For nearly 30 years, there has been a steady flow of research papers highlighting the dangers of MDMA and the implications for ecstasy users. After such a long time, it would be reasonable to expect that these dangers would be obvious due to the large number of ecstasy users. The available evidence does not indicate that there are millions of ecstasy users experiencing any problems linked to their ecstasy use. The "precautionary principle" suggests that, in the absence of knowing for certain, "experts" should argue that MDMA be avoided. However, this may have been taken too far, as the dire warnings do not seem to be reducing with the lack of epidemiological evidence of clinically relevant problems. The "ecstasy paradigm" is one way of articulating this situation, in that the needs of research funders and publication bias lead to a specific set of subcultural norms around what information is acceptable in the public domain. By digging a little deeper, it is easy to find problems with the evidence base that informs the public debate around MDMA. The key question is whether it is acceptable to maintain this status quo given the therapeutic potential of MDMA.

  7. New Indivisible Planetary Science Paradigm

    CERN Document Server

    Herndon, J Marvin

    2013-01-01

    I present here a new, indivisible planetary science paradigm, a wholly self-consistent vision of the nature of matter in the Solar System, and dynamics and energy sources of planets. Massive-core planets formed by condensing and raining-out from within giant gaseous protoplanets at high pressures and high temperatures. Earth's complete condensation included a 300 Earth-mass gigantic gas/ice shell that compressed the rocky kernel to about 66% of Earth's present diameter. T-Tauri eruptions stripped the gases away from the inner planets and stripped a portion of Mercury's incompletely condensed protoplanet, and transported it to the region between Mars and Jupiter where it fused with in-falling oxidized condensate from the outer regions of the Solar System and formed the parent matter of ordinary chondrite meteorites, the main-Belt asteroids, and veneer for the inner planets, especially Mars. In response to decompression-driven planetary volume increases, cracks form to increase surface area and mountain ranges ...

  8. Metacognition: A new cognitive paradigm

    Directory of Open Access Journals (Sweden)

    Kankaraš Miloš

    2004-01-01

    Full Text Available This article reviews concept of metacognition, defined as: (a knowledge about ones own cognitive activity, (b strategies to monitor and regulate cognitive activity and behavior, and (c subjective or metacognitive experiences which comes from some changes or temporary difficulties in cognitive functioning. While describing different conceptualizations of metacognition, its development, fields of application, relation with intelligence, and its constrictions and ambiguity, we attempt to present new and emerging metacognitive paradigm, which is, for a relatively short period, succeeded to improve, expand, and redefine wide range of theoretical and practical fields in psychology, on new and original way. How do we become conscious of our own cognitive processes? What role and significance that consciousness has, what is the functional level above thinking processes and how that level, which monitor and control cognitive activity, works. Metacognition is concept that presents, as so far, the most important insight in those human mind areas, which, although very important, remained on the margin of psychological investigations until now.

  9. Enhanced Adipogenicity of Bone Marrow Mesenchymal Stem Cells in Aplastic Anemia

    Directory of Open Access Journals (Sweden)

    Naresh Kumar Tripathy

    2014-01-01

    Full Text Available Fatty bone marrow (BM and defective hematopoiesis are a pathologic hallmark of aplastic anemia (AA. We have investigated adipogenic and osteogenic potential of BM mesenchymal stem cells (BM-MSC in 10 AA patients (08 males and 02 females with median age of 37 years (range: 06 to 79 years and in the same number of age and sex matched controls. It was observed that BM-MSC of AA patients had a morphology, phenotype, and osteogenic differentiation potential similar to control subjects but adipocytes differentiated from AA BM-MSC had a higher density and larger size of lipid droplets and they expressed significantly higher levels of adiponectin and FABP4 genes and proteins as compared to control BM-MSC (P<0.01 for both. Thus our data shows that AA BM-MSC have enhanced adipogenicity, which may have an important implication in the pathogenesis of the disease.

  10. Use of Autologous Mesenchymal Stem Cells Derived from Bone Marrow for the Treatment of Naturally Injured Spinal Cord in Dogs

    OpenAIRE

    Euler Moraes Penha; Cássio Santana Meira; Elisalva Teixeira Guimarães; Marcus Vinícius Pinheiro Mendonça; Faye Alice Gravely; Cláudia Maria Bahia Pinheiro; Taiana Maria Bahia Pinheiro; Stella Maria Barrouin-Melo; Ricardo Ribeiro-dos-Santos; Milena Botelho Pereira Soares

    2014-01-01

    The use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC) transplantation in four dogs with natural traumatic spinal cord injuries. MSC were cultured in vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten...

  11. TNF-α respecifies human mesenchymal stem cells to a neural fate and promotes migration toward experimental glioma

    OpenAIRE

    Ries, Christian; von Baumgarten, Louisa; Schichor, Christian; Berninger, Benedikt; Popp, Tanja; Neth, Peter; Goldbrunner, Roland; Kienast, Yvonne; Winkler, Frank; Jochum, Marianne; Egea, Virginia

    2010-01-01

    Abstract Bone marrow-derived human mesenchymal stem cells (hMSCs) have become valuable candidates for cell-based therapeutical applications including neuroregenerative and anti-tumor strategies. Yet, the molecular mechanisms that control hMSC transdifferentiation to neural cells and hMSC tropism toward glioma remain unclear. Here, we demonstrate that hMSCs incubated with 50 ng/ml TNF-? acquired astroglial cell morphology without affecting proliferation which was increased at 5 ng/m...

  12. Osteogenic differentiation of human mesenchymal stem cells in mineralized alginate matrices

    OpenAIRE

    Marita Westhrin; Minli Xie; Olderøy, Magnus Ø.; Pawel Sikorski; Strand, Berit L; Therese Standal

    2015-01-01

    Mineralized biomaterials are promising for use in bone tissue engineering. Culturing osteogenic cells in such materials will potentially generate biological bone grafts that may even further augment bone healing. Here, we studied osteogenic differentiation of human mesenchymal stem cells (MSC) in an alginate hydrogel system where the cells were co-immobilized with alkaline phosphatase (ALP) for gradual mineralization of the microenvironment. MSC were embedded in unmodified alginate beads and ...

  13. Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis

    OpenAIRE

    Rodriguez Jorge; Alfaro Miguel; Lara Fabian; Solano Fabio; Wang Hao; Min Wei-Ping; Ichim Thomas E; Riordan Neil H; Harman Robert J; Patel Amit N; Murphy Michael P; Lee Roland R; Minev Boris

    2009-01-01

    Abstract The stromal vascular fraction (SVF) of adipose tissue is known to contain mesenchymal stem cells (MSC), T regulatory cells, endothelial precursor cells, preadipocytes, as well as anti-inflammatory M2 macrophages. Safety of autologous adipose tissue implantation is supported by extensive use of this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose derived MSC. Equine and canine studies demonstrating anti-inflammatory and regenerative effects...

  14. Role of Wnt-5a in the Determination of Human Mesenchymal Stem Cells into Preadipocytes*

    OpenAIRE

    Bilkovski, Roman; Schulte, Dominik M.; Oberhauser, Frank; Gomolka, Matthias; Udelhoven, Michael; Hettich, Moritz M.; Roth, Bernhard; Heidenreich, Axel; Gutschow, Christian; Krone, Wilhelm; Laudes, Matthias

    2009-01-01

    Increasing adipocyte size as well as numbers is important in the development of obesity and type 2 diabetes, with adipocytes being generated from mesenchymal precursor cells. This process includes the determination of mesenchymal stem cells (MSC) into preadipocytes (PA) and the differentiation of PA into mature fat cells. Although the process of differentiation has been highly investigated, the determination in humans is poorly understood. In this study, we compared human MSC and human commit...

  15. Priming Adipose-Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Peter Succar

    2016-01-01

    Full Text Available Background. Biological therapeutics such as adipose-derived mesenchymal stem cell (MSC therapy are gaining acceptance for knee-osteoarthritis (OA treatment. Reports of OA-patients show reductions in cartilage defects and regeneration of hyaline-like-cartilage with MSC-therapy. Suspending MSCs in hyaluronan commonly occurs in animals and humans, usually without supporting data. Objective. To elucidate the effects of different concentrations of hyaluronan on MSC growth kinetics. Methods. Using a range of hyaluronan concentrations, we measured MSC adherence and proliferation on culture plastic surfaces and a novel cartilage-adhesion assay. We employed time-course and dispersion imaging to assess MSC binding to cartilage. Cytokine profiling was also conducted on the MSC-secretome. Results. Hyaluronan had dose-dependent effects on growth kinetics of MSCs at concentrations of entanglement point (1 mg/mL. At higher concentrations, viscosity effects outweighed benefits of additional hyaluronan. The cartilage-adhesion assay highlighted for the first time that hyaluronan-primed MSCs increased cell attachment to cartilage whilst the presence of hyaluronan did not. Our time-course suggested patients undergoing MSC-therapy for OA could benefit from joint-immobilisation for up to 8 hours. Hyaluronan also greatly affected dispersion of MSCs on cartilage. Conclusion. Our results should be considered in future trials with MSC-therapy using hyaluronan as a vehicle, for the treatment of OA.

  16. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells

    International Nuclear Information System (INIS)

    Mesenchymal stem cells (MSC) from mouse bone marrow were shown to adopt a pancreatic endocrine phenotype in vitro and to reverse diabetes in an animal model. MSC from human bone marrow and adipose tissue represent very similar cell populations with comparable phenotypes. Adipose tissue is abundant and easily accessible and could thus also harbor cells with the potential to differentiate in insulin producing cells. We isolated human adipose tissue-derived MSC from four healthy donors. During the proliferation period, the cells expressed the stem cell markers nestin, ABCG2, SCF, Thy-1 as well as the pancreatic endocrine transcription factor Isl-1. The cells were induced to differentiate into a pancreatic endocrine phenotype by defined culture conditions within 3 days. Using quantitative PCR a down-regulation of ABCG2 and up-regulation of pancreatic developmental transcription factors Isl-1, Ipf-1, and Ngn3 were observed together with induction of the islet hormones insulin, glucagon, and somatostatin

  17. In Vivo therapeutic potential of mesenchymal stem cell-derived extracellular vesicles with optical imaging reporter in tumor mice model.

    Science.gov (United States)

    Kalimuthu, Senthilkumar; Gangadaran, Prakash; Li, Xiu Juan; Oh, Ji Min; Lee, Ho Won; Jeong, Shin Young; Lee, Sang-Woo; Lee, Jaetae; Ahn, Byeong-Cheol

    2016-01-01

    Mesenchymal stem cells (MSCs) can be used as a therapeutic armor for cancer. Extracellular vesicles (EVs) from MSCs have been evaluated for anticancer effects. In vivo targeting of EVs to the tumor is an essential requirement for successful therapy. Therefore, non-invasive methods of monitoring EVs in animal models are crucial for developing EV-based cancer therapies. The present study to develop bioluminescent EVs using Renilla luciferase (Rluc)-expressing MSCs. The EVs from MSC/Rluc cells (EV-MSC/Rluc) were visualized in a murine lung cancer model. The anticancer effects of EVs on Lewis lung carcinoma (LLC) and other cancer cells were assessed. EV-MSC/Rluc were visualized in vivo in the LLC-efffuc tumor model using optical imaging. The induction of apoptosis was confirmed with Annexin-V and propidium iodide staining. EV-MSC/Rluc and EV-MSCs showed a significant cytotoxic effect against LLC-effluc cells and 4T1; however, no significant effect on CT26, B16F10, TC1 cells. Moreover, EV-MSC/Rluc inhibited LLC tumor growth in vivo. EV-MSC/Rluc-mediated LLC tumor inhibitory mechanism revealed the decreased pERK and increased cleaved caspase 3 and cleaved PARP. We successfully developed luminescent EV-MSC/Rluc that have a therapeutic effect on LLC cells in both in vitro and in vivo. This bioluminescent EV system can be used to optimize EV-based therapy. PMID:27452924

  18. Inter-professional work based learning within an MSc in Advanced Practice: lessons from one UK higher education programme.

    Science.gov (United States)

    Gaskell, Lynne; Beaton, Susan

    2010-09-01

    This paper will describe the implementation of inter-professional work based education (IPE) in one postgraduate Advanced Practitioner programme in the UK. The concept of Advanced Practice has developed as a response of a number of drivers including change in junior doctor training; government policy and increasing demands on the central government funded UK health service (the NHS). The programme was commissioned by the then greater Manchester Strategic Health Authority (now NHS North West) to meet service needs. The educational philosophy underpinning the MSc Advanced Practice (health and social care) provided by the University of Salford is IPE linked to work based learning. The process of work based learning (WBL) and inter-professional learning underpinning the programme will be discussed in relation to feedback from university staff, Advanced Practitioner (AP) students and employer feedback taken from programme and module evaluations. We argue that IPE at this level facilitates a greater understanding of the connectivity between professionals working in the health care system in the UK; a better understanding of the skills and knowledge base of colleagues; more inter-professional working and appropriate referrals in the work place. This has raised the profile of Advanced Practice (AP) in the region and ultimately resulted in better patient care with more effective and efficient use of resources (Acton Shapiro, 2006, 2008).

  19. Ostracism Online: A social media ostracism paradigm.

    Science.gov (United States)

    Wolf, Wouter; Levordashka, Ana; Ruff, Johanna R; Kraaijeveld, Steven; Lueckmann, Jan-Matthis; Williams, Kipling D

    2015-06-01

    We describe Ostracism Online, a novel, social media-based ostracism paradigm designed to (1) keep social interaction experimentally controlled, (2) provide researchers with the flexibility to manipulate the properties of the social situation to fit their research purposes, (3) be suitable for online data collection, (4) be convenient for studying subsequent within-group behavior, and (5) be ecologically valid. After collecting data online, we compared the Ostracism Online paradigm with the Cyberball paradigm (Williams & Jarvis Behavior Research Methods, 38, 174-180, 2006) on need-threat and mood questionnaire scores (van Beest & Williams Journal of Personality and Social Psychology 91, 918-928, 2006). We also examined whether ostracized targets of either paradigm would be more likely to conform to their group members than if they had been included. Using a Bayesian analysis of variance to examine the individual effects of the different paradigms and to compare these effects across paradigms, we found analogous effects on need-threat and mood. Perhaps because we examined conformity to the ostracizers (rather than neutral sources), neither paradigm showed effects of ostracism on conformity. We conclude that Ostracism Online is a cost-effective, easy to use, and ecologically valid research tool for studying the psychological and behavioral effects of ostracism. PMID:24878596

  20. Development of novel monoclonal antibodies that define differentiation stages of human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Andersen, Ditte Caroline; Kortesidis, Angela; Zannettino, Andrew C W;

    2011-01-01

    Human mesenchymal stem cells (hMSC) are currently being introduced for cell therapy, yet, antibodies specific for native and differentiated MSCs are required for their identification prior to clinical use. Herein, high quality antibodies against MSC surface proteins were developed by immunizing...... differentiation. Interestingly, undifferentiated cells revealed a sole cytoplasmic distribution pattern of Collagen VI, which however changed to an extracellular matrix appearance upon osteogenic- and adipogenic differentiation. In relation to this, we found that STRO-1(+/-)/Collagen VI(-) sorted hMSC contained...... fewer differentiated alkaline phosphatase(+) cells compared to STRO-1(+/-)/Collagen VI(+) hMSC, suggesting that Collagen VI on the cell membrane exclusively defines differentiated MSCs. In conclusion, we have generated a panel of high quality antibodies to be used for characterization of MSCs, and in...

  1. The cognitive paradigm ontology: design and application.

    Science.gov (United States)

    Turner, Jessica A; Laird, Angela R

    2012-01-01

    We present the basic structure of the Cognitive Paradigm Ontology (CogPO) for human behavioral experiments. While the experimental psychology and cognitive neuroscience literature may refer to certain behavioral tasks by name (e.g., the Stroop paradigm or the Sternberg paradigm) or by function (a working memory task, a visual attention task), these paradigms can vary tremendously in the stimuli that are presented to the subject, the response expected from the subject, and the instructions given to the subject. Drawing from the taxonomy developed and used by the BrainMap project ( www.brainmap.org ) for almost two decades to describe key components of published functional imaging results, we have developed an ontology capable of representing certain characteristics of the cognitive paradigms used in the fMRI and PET literature. The Cognitive Paradigm Ontology is being developed to be compliant with the Basic Formal Ontology (BFO), and to harmonize where possible with larger ontologies such as RadLex, NeuroLex, or the Ontology of Biomedical Investigations (OBI). The key components of CogPO include the representation of experimental conditions focused on the stimuli presented, the instructions given, and the responses requested. The use of alternate and even competitive terminologies can often impede scientific discoveries. Categorization of paradigms according to stimulus, response, and instruction has been shown to allow advanced data retrieval techniques by searching for similarities and contrasts across multiple paradigm levels. The goal of CogPO is to develop, evaluate, and distribute a domain ontology of cognitive paradigms for application and use in the functional neuroimaging community.

  2. Mesenchymal Stromal Cells Do Not Increase the Risk of Viral Reactivation Nor the Severity of Viral Events in Recipients of Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Giovanna Lucchini

    2012-01-01

    Full Text Available Mesenchymal stromal cells (MSC are tested in clinical trials to treat graft versus host disease (GvHD after stem cell transplantation (SCT. In vitro studies demonstrated MSC's broad immunosuppressive activity. As infections represent a major risk after SCT, it is important to understand the role of MSC in this context. We analyzed 24 patients (pts receiving MSC for GvHD in our Unit between 2009 and 2011. We recorded viral reactivations as measured in whole blood with polymerase chain reaction for 100 days following MSC administration. In patients with a documented viral reactivation in the first 3 days following MSCs infusion the frequency of virus-specific IFNgamma-producing cells was determined through enzyme-linked immunospot assay. In our cohort of patients viral reactivation after MSC infusion occurred in 45% of the cases, which did not significantly differ from the incidence in a historical cohort of patients affected by steroid resistant GvHD and treated with conventional immunosuppression. No patient presented severe form of infection. Two cases could be checked for immunological response to viral stimulus and demonstrated virus specific T-cytotoxic lymphocyte activity. In our experience MSC infusion did not prove to trigger more frequent or severer viral reactivations in the post transplantation setting.

  3. Emergence and decline of scientific paradigms

    DEFF Research Database (Denmark)

    Bornholdt, S.; Jensen, Mogens Høgh; Sneppen, Kim

    2011-01-01

    Scientific paradigms have a tendency to rise fast and decline slowly. This asymmetry reflects the difficulty in developing a truly original idea, compared to the ease at which a concept can be eroded by numerous modifications. Here we formulate a model for the emergence and spread of ideas which...... deals with this asymmetry by constraining the ability of agents to return to already abandoned concepts. The model exhibits a fairly regular pattern of global paradigm shifts, where older paradigms are eroded and subsequently replaced by new ones. The model sets the theme for a new class of pattern...

  4. Fuzzy Hybrid Deliberative/Reactive Paradigm (FHDRP)

    Science.gov (United States)

    Sarmadi, Hengameth

    2004-01-01

    This work aims to introduce a new concept for incorporating fuzzy sets in hybrid deliberative/reactive paradigm. After a brief review on basic issues of hybrid paradigm the definition of agent-based fuzzy hybrid paradigm, which enables the agents to proceed and extract their behavior through quantitative numerical and qualitative knowledge and to impose their decision making procedure via fuzzy rule bank, is discussed. Next an example performs a more applied platform for the developed approach and finally an overview of the corresponding agents architecture enhances agents logical framework.

  5. Contemporary Treatment Paradigms in Keratoconus.

    Science.gov (United States)

    McGhee, Charles N J; Kim, Bia Z; Wilson, Peter J

    2015-10-01

    The past 20 years have witnessed an explosion in our knowledge of keratoconus, accompanied by a radical transformation of management options. A 2-hit hypothesis proposes an underlying genetic predisposition coupled with external environmental factors, including eye rubbing and atopy. The variable prevalence and natural history have been better defined including significant cone progression in middle age. Therefore, current management must include early diagnosis, regular monitoring, and treatment of environmental cofactors. Spectacles and contact lenses remain fundamental to the optical management of keratoconus. Intrastromal corneal ring segments have been increasingly used, providing improvement in the corneal shape, corrected visual acuity, and contact lens wear. However, like contact lenses, intrastromal corneal ring segments do not treat the underlying disease process. Therefore, current approaches must also consider treatments to minimize keratoconus progression. Fortunately, there is increasing evidence that corneal collagen crosslinking will halt or slow progression in most cases. Until relatively recently, penetrating keratoplasty was the preferred intervention for advanced keratoconus, with long-term success in the region of 90%; however, the greatest risk of failure remains endothelial allograft rejection. Deep anterior lamellar keratoplasty has emerged in the new millennium as a preferred approach to conserve the host endothelium and avoid rejection. Nonetheless, the overall superiority of deep anterior lamellar keratoplasty compared with penetrating keratoplasty, in terms of optical and survival benefits, is still debated. This perspective provides an overview of our current knowledge of keratoconus and current management options. A step-ladder approach to managing keratoconus is outlined to provide the practitioner with a contemporary management paradigm.

  6. Gas transmission : a paradigm shift

    International Nuclear Information System (INIS)

    The evolution of energy markets in North America was discussed. The investment opportunities that are possible in a deregulated energy market, be it in production or in the generation of energy commodities, in the development of midstream infrastructure, or in the provision of energy services, were outlined. Deregulation of crude oil, natural gas and electricity has resulted in significant changes in the structure of energy markets and the way in which customers are served. One of the advantages of competition regarding power generation is that it has turned energy into a commodity which has resulted in greater customer choice and efficiency. As one example of midstream infrastructure development, the Alliance Pipeline project was described. This project was conceived as a means to enhance the value of western Canadian natural gas. The 1,900 mile pipeline will run from British Columbia, through Alberta into Chicago where it will interconnect with the North American gas transmission grid. The pipeline is an efficient means of transporting energy from Western Canada to North American markets, and Alliance, as a lowest cost transporter, will continue to put pressure on the traditional infrastructure to become even more competitive at the margin. As such, Alliance represents a paradigm shift in energy transportation, and serves as an excellent example of the type of investment opportunity that a deregulated market can provide. It was suggested that innovation and competition in a deregulated North American energy market will continue to increase. As electricity is deregulated, the energy market will respond more quickly to changes in supply and demand than it did in the past, in an effort to satisfy the needs of investors and customers. This will provide increased opportunities for restructuring and further competition

  7. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

    Directory of Open Access Journals (Sweden)

    Sean D. Owens

    2016-01-01

    Full Text Available Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM or adipose tissue derived MSCs (ad-MSCs were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89% were positive for anti-bovine serum albumin (BSA antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection.

  8. Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part II. In Vivo Imaging of Bone Marrow Stromal Cells in Swine with PET/CT and MR Imaging.

    Science.gov (United States)

    Parashurama, Natesh; Ahn, Byeong-Cheol; Ziv, Keren; Ito, Ken; Paulmurugan, Ramasamy; Willmann, Jürgen K; Chung, Jaehoon; Ikeno, Fumiaki; Swanson, Julia C; Merk, Denis R; Lyons, Jennifer K; Yerushalmi, David; Teramoto, Tomohiko; Kosuge, Hisanori; Dao, Catherine N; Ray, Pritha; Patel, Manishkumar; Chang, Ya-Fang; Mahmoudi, Morteza; Cohen, Jeff Eric; Goldstone, Andrew Brooks; Habte, Frezghi; Bhaumik, Srabani; Yaghoubi, Shahriar; Robbins, Robert C; Dash, Rajesh; Yang, Phillip C; Brinton, Todd J; Yock, Paul G; McConnell, Michael V; Gambhir, Sanjiv S

    2016-09-01

    Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone. Clinical MR imaging and PET reporter gene molecular imaging were performed after intravenous injection of the radiotracer fluorine 18-radiolabeled 9-[4-fluoro-3-(hydroxyl methyl) butyl] guanine ((18)F-FHBG). Linear regression analysis of both MR imaging and PET data and nonlinear regression analysis of PET data were performed, accounting for multiple injections per animal. Results MR imaging showed a positive correlation between MSC-TF-NP cell number and dephasing (dark) signal (R(2) = 0.72, P = .0001) and a lower detection limit of at least approximately 1.5 × 10(7) cells. PET reporter gene imaging demonstrated a significant positive correlation between MSC-TF and target-to-background ratio with the linear model (R(2) = 0.88, P = .0001, root mean square error = 0.523) and the nonlinear model (R(2) = 0.99, P = .0001, root mean square error = 0.273) and a lower detection limit of 2.5 × 10(8) cells. Conclusion The authors quantitatively determined the limit of detection of MSC after CCT in swine by using clinical PET reporter gene imaging and clinical MR imaging with cell prelabeling. (©) RSNA, 2016 Online supplemental material is available for this article. PMID:27332865

  9. 2,2,2-Trifluoroethanol changes the transition kinetics and subunit interactions in the small bacterial mechanosensitive channel MscS.

    Science.gov (United States)

    Akitake, Bradley; Spelbrink, Robin E J; Anishkin, Andriy; Killian, J Antoinette; de Kruijff, Ben; Sukharev, Sergei

    2007-04-15

    2,2,2-Trifluoroethanol (TFE), a low-dielectric solvent, has recently been used as a promising tool to probe the strength of intersubunit interactions in membrane proteins. An analysis of inner membrane proteins of Escherichia coli has identified several SDS-resistant protein complexes that separate into subunits upon exposure to TFE. One of these was the homo-heptameric stretch-activated mechanosensitive channel of small conductance (MscS), a ubiquitous component of the bacterial turgor-regulation system. Here we show that a substantial fraction of MscS retains its oligomeric state in cold lithium-dodecyl-sulfate gel electrophoresis. Exposure of MscS complexes to 10-15 vol % TFE in native membranes or nonionic detergent micelles before lithium-dodecyl-sulfate electrophoresis results in a complete dissociation into monomers, suggesting that at these concentrations TFE by itself disrupts or critically compromises intersubunit interactions. Patch-clamp analysis of giant E. coli spheroplasts expressing MscS shows that exposure to TFE in lower concentrations (0.5-5.0 vol %) causes leftward shifts of the dose-response curves when applied extracellularly, and rightward shifts when added from the cytoplasmic side. In the latter case, TFE increases the rate of tension-dependent inactivation and lengthens the process of recovery to the resting state. MscS responses to pressure ramps of different speeds indicate that in the presence of TFE most channels reside in the resting state and only at tensions near the activation threshold does TFE dramatically speed up inactivation. The effect of TFE is reversible as normal channel activity returns 15-30 min after a TFE washout. We interpret the observed midpoint shifts in terms of asymmetric partitioning of TFE into the membrane and distortion of the bilayer lateral pressure profile. We also relate the increased rate of inactivation and subunit separation with the capacity of TFE to perturb buried interhelical contacts in proteins

  10. How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?

    Directory of Open Access Journals (Sweden)

    Liangpeng Li

    2016-01-01

    Full Text Available Mesenchymal stem cell (MSC is an intensely studied stem cell type applied for cardiac repair. For decades, the preclinical researches on animal model and clinical trials have suggested that MSC transplantation exerts therapeutic effect on ischemic heart disease. However, there remain major limitations to be overcome, one of which is the very low survival rate after transplantation in heart tissue. Various strategies have been tried to improve the MSC survival, and many of them showed promising results. In this review, we analyzed the studies in recent years to summarize the methods, effects, and mechanisms of the new strategies to address this question.

  11. Mesenchymal stem cells induce T-cell tolerance and protect the preterm brain after global hypoxia-ischemia.

    Directory of Open Access Journals (Sweden)

    Reint K Jellema

    Full Text Available Hypoxic-ischemic encephalopathy (HIE in preterm infants is a severe disease for which no curative treatment is available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play a pivotal role in the etiology of white matter injury, which is the clinical hallmark of HIE in preterm infants. The objective of this study was to assess the neuroprotective and anti-inflammatory effects of intravenously delivered mesenchymal stem cells (MSC in an ovine model of HIE. In this translational animal model, global hypoxia-ischemia (HI was induced in instrumented preterm sheep by transient umbilical cord occlusion, which closely mimics the clinical insult. Intravenous administration of 2 x 10(6 MSC/kg reduced microglial proliferation, diminished loss of oligodendrocytes and reduced demyelination, as determined by histology and Diffusion Tensor Imaging (DTI, in the preterm brain after global HI. These anti-inflammatory and neuroprotective effects of MSC were paralleled by reduced electrographic seizure activity in the ischemic preterm brain. Furthermore, we showed that MSC induced persistent peripheral T-cell tolerance in vivo and reduced invasion of T-cells into the preterm brain following global HI. These findings show in a preclinical animal model that intravenously administered MSC reduced cerebral inflammation, protected against white matter injury and established functional improvement in the preterm brain following global HI. Moreover, we provide evidence that induction of T-cell tolerance by MSC might play an important role in the neuroprotective effects of MSC in HIE. This is the first study to describe a marked neuroprotective effect of MSC in a translational animal model of HIE.

  12. Effects of Oxidative Stress on Mesenchymal Stem Cell Biology

    Science.gov (United States)

    2016-01-01

    Mesenchymal stromal/stem cells (MSCs) are multipotent stem cells present in most fetal and adult tissues. Ex vivo culture-expanded MSCs are being investigated for tissue repair and immune modulation, but their full clinical potential is far from realization. Here we review the role of oxidative stress in MSC biology, as their longevity and functions are affected by oxidative stress. In general, increased reactive oxygen species (ROS) inhibit MSC proliferation, increase senescence, enhance adipogenic but reduce osteogenic differentiation, and inhibit MSC immunomodulation. Furthermore, aging, senescence, and oxidative stress reduce their ex vivo expansion, which is critical for their clinical applications. Modulation of sirtuin expression and activity may represent a method to reduce oxidative stress in MSCs. These findings have important implications in the clinical utility of MSCs for degenerative and immunological based conditions. Further study of oxidative stress in MSCs is imperative in order to enhance MSC ex vivo expansion and in vivo engraftment, function, and longevity. PMID:27413419

  13. Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences.

    Science.gov (United States)

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Alix, Philippe; Leprince, Pierre; Glejzer, Aneta; Poulet, Christophe; Hennuy, Benoit; Sommer, Lukas; Shakhova, Olga; Rogister, Bernard

    2012-08-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crest stem cells (NCSC) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSC), including their similarities and differences. In this paper, using transcriptomic as well as proteomic technologies, we compared NCSC to MSC and stromal nestin-positive cells, all of them isolated from adult bone marrow. We demonstrated that the nestin-positive cell population, which was the first to be described as able to differentiate into functional neurons, was a mixed population of NCSC and MSC. More interestingly, we demonstrated that MSC shared with NCSC the same ability to truly differentiate into Tuj1-positive cells when co-cultivated with paraformaldehyde-fixed cerebellar granule neurons. Altogether, those results suggest that both NCSC and MSC can be considered as important tools for cellular therapies in order to replace neurons in various neurological diseases. PMID:22349262

  14. The safety implications of emerging software paradigms

    International Nuclear Information System (INIS)

    This paper addresses some of the emerging software paradigms that may be used in developing safety-critical software applications. Paradigms considered in this paper include knowledge-based systems, neural networks, genetic algorithms, and fuzzy systems. It presents one view of the software verification and validation activities that should be associated with each paradigm. The paper begins with a discussion of the historical evolution of software verification and validation. Next, a comparison is made between the verification and validation processes used for conventional and emerging software systems. Several verification and validation issues for the emerging paradigms are discussed and some specific research topics are identified. This work is relevant for monitoring and control at nuclear power plants

  15. Paradigms and Principles Shaping Educational Design Research

    NARCIS (Netherlands)

    McKenney, Susan

    2014-01-01

    McKenney, S. (2013). Paradigms and Principles Shaping Educational Design Research. Invited panel presentation at the annual meeting of the European Association for Research on Learning and Instruction. August 27-31, Munich.

  16. Yakov Zeldovich and the Cosmic Web Paradigm

    CERN Document Server

    Einasto, Jaan

    2014-01-01

    I discuss the formation of the modern cosmological paradigm. In more detail I describe the early study of dark matter and cosmic web and the role of Yakov Zeldovich in the formation of the present concepts on these subjects.

  17. Engineering paradigms and anthropogenic global change

    Science.gov (United States)

    Bohle, Martin

    2016-04-01

    This essay discusses 'paradigms' as means to conceive anthropogenic global change. Humankind alters earth-systems because of the number of people, the patterns of consumption of resources, and the alterations of environments. This process of anthropogenic global change is a composite consisting of societal (in the 'noosphere') and natural (in the 'bio-geosphere') features. Engineering intercedes these features; e.g. observing stratospheric ozone depletion has led to understanding it as a collateral artefact of a particular set of engineering choices. Beyond any specific use-case, engineering works have a common function; e.g. civil-engineering intersects economic activity and geosphere. People conceive their actions in the noosphere including giving purpose to their engineering. The 'noosphere' is the ensemble of social, cultural or political concepts ('shared subjective mental insights') of people. Among people's concepts are the paradigms how to shape environments, production systems and consumption patterns given their societal preferences. In that context, engineering is a means to implement a given development path. Four paradigms currently are distinguishable how to make anthropogenic global change happening. Among the 'engineering paradigms' for anthropogenic global change, 'adaptation' is a paradigm for a business-as-usual scenario and steady development paths of societies. Applying this paradigm implies to forecast the change to come, to appropriately design engineering works, and to maintain as far as possible the current production and consumption patterns. An alternative would be to adjust incrementally development paths of societies, namely to 'dovetail' anthropogenic and natural fluxes of matter and energy. To apply that paradigm research has to identify 'natural boundaries', how to modify production and consumption patterns, and how to tackle process in the noosphere to render alterations of common development paths acceptable. A further alternative

  18. Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids

    Science.gov (United States)

    Ankrum, James A.; Dastidar, Riddhi G.; Ong, Joon Faii; Levy, Oren; Karp, Jeffrey M.

    2014-04-01

    Inadequate immunomodulatory potency of mesenchymal stem cells (MSC) may limit their therapeutic efficacy. We report glucocorticoid steroids augment MSC expression and activity of indoleamine-2,3-dioxygenase (IDO), a primary mediator of MSC immunomodulatory function. This effect depends on signaling through the glucocorticoid receptor and is mediated through up-regulation of FOXO3. Treatment of MSCs with glucocorticoids, budesonide or dexamethasone, enhanced IDO expression following IFN-γ stimulation in multiple donors and was able to restore IDO expression in over-passaged MSCs. As IDO enhancement was most notable when cells were continuously exposed to budesonide, we engineered MSC with budesonide loaded PLGA microparticles. MSC efficiently internalized budesonide microparticles and exhibited 4-fold enhanced IDO activity compared to budesonide preconditioned and naïve MSC, resulting in a 2-fold improvement in suppression of stimulated peripheral blood mononuclear cells in an IDO-dependent manner. Thus, the augmentation of MSC immune modulation may abrogate challenges associated with inadequate potency and enhance their therapeutic efficacy.

  19. Identification of Pathways in Liver Repair Potentially Targeted by Secretory Proteins from Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Sandra Winkler

    2016-07-01

    Full Text Available Background: The beneficial impact of mesenchymal stem cells (MSC on both acute and chronic liver diseases has been confirmed, although the molecular mechanisms behind it remain elusive. We aim to identify factors secreted by undifferentiated and hepatocytic differentiated MSC in vitro in order to delineate liver repair pathways potentially targeted by MSC. Methods: Secreted factors were determined by protein arrays and related pathways identified by biomathematical analyses. Results: MSC from adipose tissue and bone marrow expressed a similar pattern of surface markers. After hepatocytic differentiation, CD54 (intercellular adhesion molecule 1, ICAM-1 increased and CD166 (activated leukocyte cell adhesion molecule, ALCAM decreased. MSC secreted different factors before and after differentiation. These comprised cytokines involved in innate immunity and growth factors regulating liver regeneration. Pathway analysis revealed cytokine-cytokine receptor interactions, chemokine signalling pathways, the complement and coagulation cascades as well as the Januskinase-signal transducers and activators of transcription (JAK-STAT and nucleotide-binding oligomerization domain-like receptor (NOD-like receptor signalling pathways as relevant networks. Relationships to transforming growth factor β (TGF-β and hypoxia-inducible factor 1-α (HIF1-α signalling seemed also relevant. Conclusion: MSC secreted proteins, which differed depending on cell source and degree of differentiation. The factors might address inflammatory and growth factor pathways as well as chemo-attraction and innate immunity. Since these are prone to dysregulation in most liver diseases, MSC release hepatotropic factors, potentially supporting liver regeneration.

  20. International business and the eclectic paradigm

    DEFF Research Database (Denmark)

    The eclectic paradigm has become the dominant theoretical basis in the study of international business, multinational corporations and internationalization since 1980. However, developments such as economic globalization and the subsequent growth of global and alliance capitalism have fundamentally......, finance, evolutionary economics, resource-based theory or strategic management? Can it be utilized to explain new developments in international business and economics? Do these require new ideas and concepts to be integrated within the eclectic paradigm? What are the new challenges to which international...

  1. A regulatory cross-talk between Vgamma9Vdelta2 T lymphocytes and mesenchymal stem cells.

    Science.gov (United States)

    Martinet, Ludovic; Fleury-Cappellesso, Sandrine; Gadelorge, Mélanie; Dietrich, Gilles; Bourin, Philippe; Fournié, Jean-Jacques; Poupot, Rémy

    2009-03-01

    The physiological functions of human TCRVgamma9Vdelta2(+) gammadelta lymphocytes reactive to non-peptide phosphoantigens contribute to cancer immunosurveillance and immunotherapy. However, their regulation by mesenchymal stem cells (MSC), multipotent and immunomodulatory progenitor cells able to infiltrate tumors, has not been investigated so far. By analyzing freshly isolated TCRVgamma9Vdelta2(+) lymphocytes and primary cell lines stimulated with synthetic phosphoantigen or B-cell lymphoma cell lines in the presence of MSC, we demonstrated that MSC were potent suppressors of gammadelta-cell proliferation, cytokine production and cytolytic responses in vitro. This inhibition was mediated by the COX-2-dependent production of prostaglandin E2 (PGE(2)) and by MSC through EP2 and EP4 inhibitory receptors expressed by Vgamma9Vdelta2 T lymphocytes. COX-2 expression and PGE(2) production by MSC were not constitutive, but were induced by IFN-gamma and TNF-alpha secreted by activated Vgamma9Vdelta2 T cells. This regulatory cross-talk between MSC and Vgamma9Vdelta2 T lymphocytes involving PGE(2) could be of importance for the antitumor and antimicrobial activities of gammadelta T cells.

  2. New Indivisible Planetary Science Paradigm: Consequence of Questioning Popular Paradigms

    Science.gov (United States)

    Marvin Herndon, J.

    2014-05-01

    Progress in science involves replacing less precise understanding with more precise understanding. In science and in science education one should always question popular ideas; ask "What's wrong with this picture?" Finding limitations, conflicts or circumstances that require special ad hoc consideration sometimes is the key to making important discoveries. For example, from thermodynamic considerations, I found that the 'standard model of solar system formation' leads to insufficiently massive planetary cores. That understanding led me to discover a new indivisible planetary science paradigm. Massive-core planets formed by condensing and raining-out from within giant gaseous protoplanets at high pressures and high temperatures, accumulating heterogeneously on the basis of volatility with liquid core-formation preceding mantle-formation; the interior states of oxidation resemble that of the Abee enstatite chondrite. Core-composition was established during condensation based upon the relative solubilities of elements, including uranium, in liquid iron in equilibrium with an atmosphere of solar composition at high pressures and high temperatures. Uranium settled to the central region and formed planetary nuclear fission reactors, producing heat and planetary magnetic fields. Earth's complete condensation included a ~300 Earth-mass gigantic gas/ice shell that compressed the rocky kernel to about 66% of Earth's present diameter. T-Tauri eruptions, associated with the thermonuclear ignition of the Sun, stripped the gases away from the Earth and the inner planets. The T-Tauri outbursts stripped a portion of Mercury's incompletely condensed protoplanet and transported it to the region between Mars and Jupiter where it fused with in-falling oxidized condensate from the outer regions of the Solar System, forming the parent matter of ordinary chondrite meteorites, the main-Belt asteroids, and veneer for the inner planets, especially Mars. With its massive gas/ice shell

  3. Phenanthroline treated MSC

    NARCIS (Netherlands)

    Fernandes, H.A.M.; Boer, de J.; Quax, P.H.A.; Doorn, J.

    2013-01-01

    The invention relates to the field of medicine and in particular to the treatment of ischemia and to angiogenesis. The invention further relates to novel uses of phenanthroline in replacing a missing biological structure, supporting a damaged biological structure and/or enhancing an existing biologi

  4. The Underlying Social Dynamics of Paradigm Shifts

    Science.gov (United States)

    Claro, Francisco; Fuentes, Miguel Angel

    2015-01-01

    We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution) within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i) marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm); and ii) radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology) that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm. PMID:26418255

  5. The Underlying Social Dynamics of Paradigm Shifts.

    Directory of Open Access Journals (Sweden)

    Carlos Rodriguez-Sickert

    Full Text Available We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm; and ii radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

  6. The Underlying Social Dynamics of Paradigm Shifts.

    Science.gov (United States)

    Rodriguez-Sickert, Carlos; Cosmelli, Diego; Claro, Francisco; Fuentes, Miguel Angel

    2015-01-01

    We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution) within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i) marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm); and ii) radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology) that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

  7. Half-metallic ferromagnetism in chalcopyrite type compounds ZnMX{sub 2} (M=Sc, V, Mn, Fe; X = P, As)

    Energy Technology Data Exchange (ETDEWEB)

    Vijayalakshmi, D.; Kalpana, G., E-mail: g-kalpa@yahoo.com, E-mail: g-kalpa@annauniv.edu [Department of Physics, Anna University, Chennai – 600025 (India)

    2015-06-24

    Electronic structure and magnetic properties of ZnMX{sub 2} (M=Sc, V, Mn and Fe; X= As and P) compounds in body centred tetragonal chalcopyrite structure have been investigated using first-principles calculations based on density functional theory (DFT) within the local spin density approximation (LSDA). The spin-polarized electronic band structure and density of states of all these compounds show that the spin-up electrons have metallic and the spin-down electrons have a semiconducting gap and the magnetic moment mainly originates from the strong spin polarization of 3d states of transition metal (M=Sc, V, Mn and Fe) atoms and p-like states of anion X (P and As) atoms.

  8. Marijuana smoke condensate induces p53-mediated apoptosis in human lung epithelial cells.

    Science.gov (United States)

    Kim, Ha Ryong; Jung, Mi Hyun; Lee, Soo Yeun; Oh, Seung Min; Chung, Kyu Hyuck

    2013-01-01

    Since the largely abused worldwide used of marijuana, there have been many ongoing debates regarding the adverse health effects of marijuana smoking. Marijuana smoking was recently proved to cause pulmonary toxicity by inducing genotoxic effects or generating reactive oxygen species. Because p53, a tumor suppressor gene, has an important pathophysiologic role in the regulation of lung epithelial cell DNA damage responses, we hypothesized that p53 may be involved in the oxidative stress-mediated apoptosis induced by marijuana smoking. First, we confirmed that marijuana smoke condensate (MSC) induces oxidative stress in BEAS-2B cells. We observed that reactive oxygen species (ROS) generation was increased by MSC in the DCFH-DA assay. Also, antioxidant enzyme (superoxide dismutase, catalase) activity and their mRNA expressions were up-regulated by MSC. Second, we investigated p53 involvement in the MSC-induced apoptotic pathway in BEAS-2B cells. The results showed that MSC increased caspase-3 activation and DNA fragmentation as markers of apoptosis. In addition, the mRNA levels of apoptosis-related genes (p53 and Bax) were increased by MSC and phospho-p53, along with the increase of Bax protein expression by MSC. Apoptosis and apoptosis-related gene expression were partially blocked by an inhibitor of p53-dependent transcriptional activation (pifithrin-α). The results indicate that p53 plays a role in MSC-induced apoptosis. Taken together, the findings of the present study suggest that MSC partially induces p53-mediated apoptosis through ROS generation in human lung epithelial cells and this may have broader implications for our understanding of pulmonary diseases. PMID:23665932

  9. Evaluation of intrarenal mesenchymal stem cell injection for treatment of chronic kidney disease in cats: a pilot study.

    Science.gov (United States)

    Quimby, Jessica M; Webb, Tracy L; Gibbons, Debra S; Dow, Steven W

    2011-06-01

    The feasibility of autologous intrarenal mesenchymal stem cell (MSC) therapy in cats with chronic kidney disease (CKD) was investigated. Six cats (two healthy, four with CKD) received a single unilateral intrarenal injection of autologous bone marrow-derived or adipose tissue-derived MSC (bmMSC or aMSC) via ultrasound guidance. Minimum database and glomerular filtration rate (GFR) via nuclear scintigraphy were determined pre-injection, at 7 days and at 30 days post-injection. Intrarenal injection did not induce immediate or long-term adverse effects. Two cats with CKD that received aMSC experienced modest improvement in GFR and a mild decrease in serum creatinine concentration. Despite the possible benefits of intrarenal MSC injections for CKD cats, the number of sedations and interventions required to implement this approach would likely preclude widespread clinical application. We concluded that MSC could be transferred safely by ultrasound-guided intrarenal injection in cats, but that alternative sources and routes of MSC therapy should be investigated. PMID:21334237

  10. Effect of human umbilical cord mesenchymal stem cell-secretion on proliferation and apoptosis in hepatocytes%人脐带间充质干细胞分泌物对肝细胞增殖和凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    黎娇; 朱争艳; 杜智; 骆莹; 王鹏; 高英堂

    2010-01-01

    目的 探讨人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,HUC MSC)旁分泌物质在体外对肝细胞再生和凋亡的影响.方法 利用Ⅳ型胶原酶和胰酶消化法从脐带中分离间充质干细胞,制备含有HUCMSC旁分泌物质的条件培养基(mesenchymal stem cells-conditioned medium,MSC-CM),采用低浓度胶原酶原位循环灌流法分离肝细胞.试验分为对照组、2%MSC-CM组和8%MSC-CM组三组.采用MTT比色法观察不同浓度MSC-CM对正常肝细胞增殖的影响.测定上清中尿素、白蛋白的含量,观察不同浓度MSC-CM对肝细胞功能的影响.利用放线菌素D和肿瘤坏死因子α诱导肝细胞凋亡,采用细胞活性分析试剂盒检测不同浓度MSC-CM对肝细胞凋亡的影响.结果 与对照组比较,2%MSC-CM组吸光度(A)540nm值(P<0.01)以及上清尿素和白蛋白含量显著升高(P<0.01),肝细胞存活率增加(P<0.05);8%MSC-CM组与对照组无显著差异.结论 低浓度的MSC-CM在体外可以刺激正常肝细胞再生,抑制受损肝细胞凋亡,改善肝细胞功能.%Objective To investigate the effect of human umbilical cord mesenchymal stem cell paracrine substance on proliferation and apoptosis of liver cells in vitro. Methods Mesenchymal stem cells (MSC)were separated from human umbilical cord with type Ⅳ collagenase and trypsogen digestion method and cultured in vitro. The human umbilical cord mesenchymal stem cells-conditioned medium(MSC-CM) which contain paracrine substance of human umbilical cord mesenchymal stem cells (HUCMSC) was prepared. Hepatocytes were isolated from SD rats by low concentration collagenase perfusion procedure. There were three groups in the experiment, control group, 2% MSC-CM group and 8% MSC-CM group. The proliferation of normal hepatocytes were assayed with MTT method. We detected the urea and albumin level in culture supernatant to assay the hepatocyte function under different concentration MSC-CM. Hepatocytes were

  11. The effect of a chitosan-gelatin matrix and dexamethasone on the behavior of rabbit mesenchymal stem cells

    International Nuclear Information System (INIS)

    Cartilage tissue has poor capability of self-repair, especially in the case of severe cartilage damage due to trauma or age-related degeneration. Cell-based tissue engineering using scaffolds has provided an option for the repair of defects in adult cartilage tissue. Mesenchymal stem cells (MSC) and chondrocytes are the two major cell sources for cartilage tissue engineering. The present study combined culture conditions of MSC in a chitosan-gelatin matrix in chondrogenic media to evaluate their effects on MSC viability and chondrogenesis for cartilage tissue engineering. MSC were harvested from rabbit bone marrows and cultured in chondrogenic media supplemented, or not, with dexamethasone in a chitosan-gelatin film (C-GF). The association of C-GF and dexamethasone promoted significant increase in cell adhesivity, viability and proliferation when compared to MCS cultured in media without dexamethasone or C-GF. In addition, dexamethasone promoted increase in the collagen concentration of MSC cultures. A reduction of alkaline phosphatase activity after three weeks of culture in chondrogenic media was verified. No influence of the C-GF or of dexamethasone was observed in this matter. Therefore, it is reasonable to suggest that biomaterial-based chitosan-gelatin and chondrogenic media supplemented with dexamethasone may stimulate the proliferation and differentiation of MSC according to the complex environmental conditions. The information presented here should be useful for the development of biomaterials to regulate the chondrogenesis of MSC suitable for cartilage tissue engineering

  12. The effect of a chitosan-gelatin matrix and dexamethasone on the behavior of rabbit mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Medrado, G C B [Medicine School, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Machado, C B [Biochemistry and Immunology Department, Biological Sciences Institute, UFMG - Federal University of Minas Gerais, mailbox 486, zip code 31270-901, Belo Horizonte, MG (Brazil); Valerio, P [Biochemistry and Immunology Department, Biological Sciences Institute, UFMG - Federal University of Minas Gerais, mailbox 486, zip code 31270-901, Belo Horizonte, MG (Brazil); Sanches, M D [Medicine School, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Goes, A M [Biochemistry and Immunology Department, Biological Sciences Institute, UFMG - Federal University of Minas Gerais, mailbox 486, zip code 31270-901, Belo Horizonte, MG (Brazil)

    2006-09-15

    Cartilage tissue has poor capability of self-repair, especially in the case of severe cartilage damage due to trauma or age-related degeneration. Cell-based tissue engineering using scaffolds has provided an option for the repair of defects in adult cartilage tissue. Mesenchymal stem cells (MSC) and chondrocytes are the two major cell sources for cartilage tissue engineering. The present study combined culture conditions of MSC in a chitosan-gelatin matrix in chondrogenic media to evaluate their effects on MSC viability and chondrogenesis for cartilage tissue engineering. MSC were harvested from rabbit bone marrows and cultured in chondrogenic media supplemented, or not, with dexamethasone in a chitosan-gelatin film (C-GF). The association of C-GF and dexamethasone promoted significant increase in cell adhesivity, viability and proliferation when compared to MCS cultured in media without dexamethasone or C-GF. In addition, dexamethasone promoted increase in the collagen concentration of MSC cultures. A reduction of alkaline phosphatase activity after three weeks of culture in chondrogenic media was verified. No influence of the C-GF or of dexamethasone was observed in this matter. Therefore, it is reasonable to suggest that biomaterial-based chitosan-gelatin and chondrogenic media supplemented with dexamethasone may stimulate the proliferation and differentiation of MSC according to the complex environmental conditions. The information presented here should be useful for the development of biomaterials to regulate the chondrogenesis of MSC suitable for cartilage tissue engineering.

  13. Stem cell therapy for inflammatory bowel disease

    NARCIS (Netherlands)

    Duijvestein, Marjolijn

    2012-01-01

    Hematopoietic stem cell transplantation (HSCT) and mesenchymal stromal (MSC) cell therapy are currently under investigation as novel therapies for inflammatory bowel diseases (IBD). Hematopoietic stem cells are thought to repopulate the immune system and reset the immunological response to luminal a

  14. Molecular characterisation of stromal populations derived from human embryonic stem cells

    DEFF Research Database (Denmark)

    Harkness, L.; Twine, N. A.; Abu Dawud, R.;

    2015-01-01

    of hESC-stromal and immortalised BM-hMSC cells (hMSC-TERT). Of the 7379 genes expressed above baseline, only 9.3% of genes were differentially expressed between undifferentiated hESC-stromal and BM-hMSC. Following ex vivo osteoblast induction, 665 and 695 genes exhibited >. 2-fold change (FC) in h......ESC-stromal and BM-hMSC, respectively with 172 genes common to both cell types. Functional annotation of significantly changing genes revealed similarities in gene ontology between the two cell types. Interestingly, genes in categories of cell adhesion/motility and epithelial-mesenchymal transition (EMT) were highly...... enriched in hESC-stromal whereas genes associated with cell cycle processes were enriched in hMSC-TERT. This data suggests that while hESC-stromal cells exhibit a similar molecular phenotype to hMSC-TERT, differences exist that can be explained by ontological differences between these two cell types. h...

  15. Spatial organization of mesenchymal stem cells in vitro--results from a new individual cell-based model with podia.

    Directory of Open Access Journals (Sweden)

    Martin Hoffmann

    Full Text Available Therapeutic application of mesenchymal stem cells (MSC requires their extensive in vitro expansion. MSC in culture typically grow to confluence within a few weeks. They show spindle-shaped fibroblastoid morphology and align to each other in characteristic spatial patterns at high cell density. We present an individual cell-based model (IBM that is able to quantitatively describe the spatio-temporal organization of MSC in culture. Our model substantially improves on previous models by explicitly representing cell podia and their dynamics. It employs podia-generated forces for cell movement and adjusts cell behavior in response to cell density. At the same time, it is simple enough to simulate thousands of cells with reasonable computational effort. Experimental sheep MSC cultures were monitored under standard conditions. Automated image analysis was used to determine the location and orientation of individual cells. Our simulations quantitatively reproduced the observed growth dynamics and cell-cell alignment assuming cell density-dependent proliferation, migration, and morphology. In addition to cell growth on plain substrates our model captured cell alignment on micro-structured surfaces. We propose a specific surface micro-structure that according to our simulations can substantially enlarge cell culture harvest. The 'tool box' of cell migratory behavior newly introduced in this study significantly enhances the bandwidth of IBM. Our approach is capable of accommodating individual cell behavior and collective cell dynamics of a variety of cell types and tissues in computational systems biology.

  16. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    OpenAIRE

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Peter J Nelson; Bruns, Christiane J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associa...

  17. Human Mesenchymal Stem Cells Genetically Engineered to Overexpress Brain-derived Neurotrophic Factor Improve Outcomes in Huntington's Disease Mouse Models.

    Science.gov (United States)

    Pollock, Kari; Dahlenburg, Heather; Nelson, Haley; Fink, Kyle D; Cary, Whitney; Hendrix, Kyle; Annett, Geralyn; Torrest, Audrey; Deng, Peter; Gutierrez, Joshua; Nacey, Catherine; Pepper, Karen; Kalomoiris, Stefanos; D Anderson, Johnathon; McGee, Jeannine; Gruenloh, William; Fury, Brian; Bauer, Gerhard; Duffy, Alexandria; Tempkin, Theresa; Wheelock, Vicki; Nolta, Jan A

    2016-05-01

    Huntington's disease (HD) is a fatal degenerative autosomal dominant neuropsychiatric disease that causes neuronal death and is characterized by progressive striatal and then widespread brain atrophy. Brain-derived neurotrophic factor (BDNF) is a lead candidate for the treatment of HD, as it has been shown to prevent cell death and to stimulate the growth and migration of new neurons in the brain in transgenic mouse models. BDNF levels are reduced in HD postmortem human brain. Previous studies have shown efficacy of mesenchymal stem/stromal cells (MSC)/BDNF using murine MSCs, and the present study used human MSCs to advance the therapeutic potential of the MSC/BDNF platform for clinical application. Double-blinded studies were performed to examine the effects of intrastriatally transplanted human MSC/BDNF on disease progression in two strains of immune-suppressed HD transgenic mice: YAC128 and R6/2. MSC/BDNF treatment decreased striatal atrophy in YAC128 mice. MSC/BDNF treatment also significantly reduced anxiety as measured in the open-field assay. Both MSC and MSC/BDNF treatments induced a significant increase in neurogenesis-like activity in R6/2 mice. MSC/BDNF treatment also increased the mean lifespan of the R6/2 mice. Our genetically modified MSC/BDNF cells set a precedent for stem cell-based neurotherapeutics and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis, Alzheimer's disease, and some forms of Parkinson's disease. These cells provide a platform delivery system for future studies involving corrective gene-editing strategies. PMID:26765769

  18. Mesenchymal Stem Cell-Derived Exosomes: New Opportunity in Cell-Free Therapy

    Science.gov (United States)

    Pashoutan Sarvar, Davod; Shamsasenjan, Karim; Akbarzadehlaleh, Parvin

    2016-01-01

    Mesenchymal stromal/stem cells (MSCs) are involved in tissue homeostasis through direct cell-to-cell interaction, as well as secretion of soluble factors. Exosomes are the sort of soluble biological mediators that obtained from MSCs cultured media in vitro. MSC-derived exosomes (MSC-DEs) which produced under physiological or pathological conditions are central mediators of intercellular communications by conveying proteins, lipids, mRNAs, siRNA, ribosomal RNAs and miRNAs to the neighbor or distant cells. MSC-DEs have been tested in various disease models, and the results have revealed that their functions are similar to those of MSCs. They have the supportive functions in organisms such as repairing tissue damages, suppressing inflammatory responses, and modulating the immune system. MSC-DEs are of great interest in the scope of regenerative medicine because of their unique capacity to the regeneration of the damaged tissues, and the present paper aims to introduce MSC-DEs as a novel hope in cell-free therapy.

  19. Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization

    DEFF Research Database (Denmark)

    Elsafadi, E; Manikandan, M; Dawud, RA;

    2016-01-01

    bone marrow-derived stromal (skeletal) stem cells (hMSC). siRNA-mediated gene silencing of TAGLN impaired lineage differentiation into osteoblasts and adipocytes but enhanced cell proliferation. Additional functional studies revealed that TAGLN deficiency impaired hMSC cell motility and in vitro...... transwell cell migration. On the other hand, TAGLN overexpression reduced hMSC cell proliferation, but enhanced cell migration, osteoblastic and adipocytic differentiation, and in vivo bone formation. In addition, deficiency or overexpression of TAGLN in hMSC was associated with significant changes...... in cellular and nuclear morphology and cytoplasmic organelle composition as demonstrated by high content imaging and transmission electron microscopy that revealed pronounced alterations in the distribution of the actin filament and changes in cytoskeletal organization. Molecular signature of TAGLN...

  20. ENVIRONMENTALISM AND CLASSIC PARADIGMS OF INTERNATIONAL RELATIONS

    Directory of Open Access Journals (Sweden)

    D. D. Miniaeva

    2014-06-01

    Full Text Available This article examines an environmentalism integration process into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism. The main purpose of this study is to reveal the result of this integration. Methods used in this article include analysis and comparison of "ecological" paradigms on selected parameters (the nature of international relations, actors, targets, tools, processes. Results of research show that the beginning of the XXI century is distinguished by the development of new types of political concepts that explain interaction of elements in modern international relations in the area of environmental protection. The reason of these changes lies in the phenomena of environmentalism integration into Three paradigms of international relations. However, we cannot say that any of the examined paradigms accumulated all features of environmentalism without their modification. Better to say, it's rather similar to adaptation of environmental ideas. Therefore, to understand modern international relations processes, it is necessary to take into account their environmental element. Purchase on Elibrary.ru > Buy nowDOI: http://dx.doi.org/10.12731/2070-7568-2014-3-4

  1. Molecular characterisation of stromal populations derived from human embryonic stem cells

    DEFF Research Database (Denmark)

    Harkness, L.; Twine, N. A.; Abu Dawud, R.;

    2015-01-01

    Human bone marrow-derived stromal (skeletal) stem cells (BM-hMSC) are being employed in an increasing number of clinical trials for tissue regeneration. A limiting factor for their clinical use is the inability to obtain sufficient cell numbers. Human embryonic stem cells (hESC) can provide...... an unlimited source of clinical grade cells for therapy. We have generated MSC-like cells from hESC (called here hESC-stromal) that exhibit surface markers and differentiate to osteoblasts and adipocytes, similar to BM-hMSC. In the present study, we used microarray analysis to compare the molecular phenotype...... of hESC-stromal and immortalised BM-hMSC cells (hMSC-TERT). Of the 7379 genes expressed above baseline, only 9.3% of genes were differentially expressed between undifferentiated hESC-stromal and BM-hMSC. Following ex vivo osteoblast induction, 665 and 695 genes exhibited >. 2-fold change (FC) in h...

  2. Gene expression changes in the injured spinal cord following transplantation of mesenchymal stem cells or olfactory ensheathing cells.

    Directory of Open Access Journals (Sweden)

    Abel Torres-Espín

    Full Text Available Transplantation of bone marrow derived mesenchymal stromal cells (MSC or olfactory ensheathing cells (OEC have demonstrated beneficial effects after spinal cord injury (SCI, providing tissue protection and improving the functional recovery. However, the changes induced by these cells after their transplantation into the injured spinal cord remain largely unknown. We analyzed the changes in the spinal cord transcriptome after a contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. The gene profiles were analyzed by clustering and functional enrichment analysis based on the Gene Ontology database. We found that both MSC and OEC transplanted acutely after injury induce an early up-regulation of genes related to tissue protection and regeneration. In contrast, cells transplanted at 7 days after injury down-regulate genes related to tissue regeneration. The most important change after MSC or OEC transplant was a marked increase in expression of genes associated with foreign body response and adaptive immune response. These data suggest a regulatory effect of MSC and OEC transplantation after SCI regarding tissue repair processes, but a fast rejection response to the grafted cells. Our results provide an initial step to determine the mechanisms of action and to optimize cell therapy for SCI.

  3. Simvastatin modulates mesenchymal stromal cell proliferation and gene expression.

    Directory of Open Access Journals (Sweden)

    Dalila Lucíola Zanette

    Full Text Available Statins are widely used hypocholesterolemic drugs that block the mevalonate pathway, responsible for the biosysnthesis of cholesterol. However, statins also have pleiotropic effects that interfere with several signaling pathways. Mesenchymal stromal cells (MSC are a heterogeneous mixture of cells that can be isolated from a variety of tissues and are identified by the expression of a panel of surface markers and by their ability to differentiate in vitro into osteocytes, adipocytes and chondrocytes. MSC were isolated from amniotic membranes and bone marrows and characterized based on ISCT (International Society for Cell Therapy minimal criteria. Simvastatin-treated cells and controls were directly assayed by CFSE (Carboxyfluorescein diacetate succinimidyl ester staining to assess their cell proliferation and their RNA was used for microarray analyses and quantitative PCR (qPCR. These MSC were also evaluated for their ability to inhibit PBMC (peripheral blood mononuclear cells proliferation. We show here that simvastatin negatively modulates MSC proliferation in a dose-dependent way and regulates the expression of proliferation-related genes. Importantly, we observed that simvastatin increased the percentage of a subset of smaller MSC, which also were actively proliferating. The association of MSC decreased size with increased pluripotency and the accumulating evidence that statins may prevent cellular senescence led us to hypothesize that simvastatin induces a smaller subpopulation that may have increased ability to maintain the entire pool of MSC and also to protect them from cellular senescence induced by long-term cultures/passages in vitro. These results may be important to better understand the pleiotropic effects of statins and its effects on the biology of cells with regenerative potential.

  4. Organizational improvement using Organizational paradigms with the support of people paradigms

    Directory of Open Access Journals (Sweden)

    Md. Shariful Alam

    2011-02-01

    Full Text Available An organization is a vital part of social environment. Different parts of organization have great impact to the environment. On the other hand the different organizational strategy helps to improve the efficiency of organization and customer satisfaction. The people and tools of organization help to organization to work properly. This paper mainly describes about the organizational paradigms and people paradigms also the way how the people paradigms facilitate the organizational paradigms to improve the organizational architecture for better performance. This paper describes the different aspects of organizational like Information system strategy, Information system planning, Business process reengineering etc also End user computing, Knowledge management, Expert system of people paradigms.And finally there is a combination between those. Keywords: Business process reengineering, Customer satisfaction, end used computing, In Information System Strategy, knowledge management, Organizational improvement.

  5. Mesenchymal Stem Cells Do Not Prevent Antibody Responses against Human α-L-Iduronidase when Used to Treat Mucopolysaccharidosis Type I

    Science.gov (United States)

    Martin, Priscila Keiko Matsumoto; Stilhano, Roberta Sessa; Samoto, Vivian Yochiko; Takiya, Christina Maeda; Peres, Giovani Bravin; da Silva Michelacci, Yara Maria Correa; da Silva, Flavia Helena; Pereira, Vanessa Gonçalves; D'Almeida, Vânia; Marques, Fabio Luiz Navarro; Otake, Andreia Hanada; Chammas, Roger; Han, Sang Won

    2014-01-01

    Mucopolysaccharidosis type I (MPSI) is an autosomal recessive disease that leads to systemic lysosomal storage, which is caused by the absence of α-L-iduronidase (IDUA). Enzyme replacement therapy is recognized as the best therapeutic option for MPSI; however, high titers of anti-IDUA antibody have frequently been observed. Due to the immunosuppressant properties of MSC, we hypothesized that MSC modified with the IDUA gene would be able to produce IDUA for a long period of time. Sleeping Beauty transposon vectors were used to modify MSC because these are basically less-immunogenic plasmids. For cell transplantation, 4×106 MSC-KO-IDUA cells (MSC from KO mice modified with IDUA) were injected into the peritoneum of KO-mice three times over intervals of more than one month. The total IDUA activities from MSC-KO-IDUA before cell transplantation were 9.6, 120 and 179 U for the first, second and third injections, respectively. Only after the second cell transplantation, more than one unit of IDUA activity was detected in the blood of 3 mice for 2 days. After the third cell transplantation, a high titer of anti-IDUA antibody was detected in all of the treated mice. Anti-IDUA antibody response was also detected in C57Bl/6 mice treated with MSC-WT-IDUA. The antibody titers were high and comparable to mice that were immunized by electroporation. MSC-transplanted mice had high levels of TNF-alpha and infiltrates in the renal glomeruli. The spreading of the transplanted MSC into the peritoneum of other organs was confirmed after injection of 111In-labeled MSC. In conclusion, the antibody response against IDUA could not be avoided by MSC. On the contrary, these cells worked as an adjuvant that favored IDUA immunization. Therefore, the humoral immunosuppressant property of MSC is questionable and indicates the danger of using MSC as a source for the production of exogenous proteins to treat monogenic diseases. PMID:24642723

  6. Mesenchymal stem cells do not prevent antibody responses against human α-L-iduronidase when used to treat mucopolysaccharidosis type I.

    Directory of Open Access Journals (Sweden)

    Priscila Keiko Matsumoto Martin

    Full Text Available Mucopolysaccharidosis type I (MPSI is an autosomal recessive disease that leads to systemic lysosomal storage, which is caused by the absence of α-L-iduronidase (IDUA. Enzyme replacement therapy is recognized as the best therapeutic option for MPSI; however, high titers of anti-IDUA antibody have frequently been observed. Due to the immunosuppressant properties of MSC, we hypothesized that MSC modified with the IDUA gene would be able to produce IDUA for a long period of time. Sleeping Beauty transposon vectors were used to modify MSC because these are basically less-immunogenic plasmids. For cell transplantation, 4×10(6 MSC-KO-IDUA cells (MSC from KO mice modified with IDUA were injected into the peritoneum of KO-mice three times over intervals of more than one month. The total IDUA activities from MSC-KO-IDUA before cell transplantation were 9.6, 120 and 179 U for the first, second and third injections, respectively. Only after the second cell transplantation, more than one unit of IDUA activity was detected in the blood of 3 mice for 2 days. After the third cell transplantation, a high titer of anti-IDUA antibody was detected in all of the treated mice. Anti-IDUA antibody response was also detected in C57Bl/6 mice treated with MSC-WT-IDUA. The antibody titers were high and comparable to mice that were immunized by electroporation. MSC-transplanted mice had high levels of TNF-alpha and infiltrates in the renal glomeruli. The spreading of the transplanted MSC into the peritoneum of other organs was confirmed after injection of 111In-labeled MSC. In conclusion, the antibody response against IDUA could not be avoided by MSC. On the contrary, these cells worked as an adjuvant that favored IDUA immunization. Therefore, the humoral immunosuppressant property of MSC is questionable and indicates the danger of using MSC as a source for the production of exogenous proteins to treat monogenic diseases.

  7. Immune Mechanisms of Mesenchymal Stem Cell Therapy for Acute Graft versus Host Disease

    OpenAIRE

    Tobin, Laura M.

    2012-01-01

    The aim of this work was to investigate the role of Mesenchymal stem cells (MSC) in the modulation of immune responses, focusing on suppression and induction of immune tolerance. To date, MSC therapy has proved beneficial for the treatment of inflammatory and autoimmune diseases, such as acute Graft versus Host Disease (aGvHD) and Crohn’s disease. However, the exact mechanisms of therapeutic benefit remain unclear. The key goals of this study were to identify the role of MSC derived soluble a...

  8. Emergence and decline of scientific paradigms.

    Science.gov (United States)

    Bornholdt, S; Jensen, M H; Sneppen, K

    2011-02-01

    Scientific paradigms have a tendency to rise fast and decline slowly. This asymmetry reflects the difficulty in developing a truly original idea, compared to the ease at which a concept can be eroded by numerous modifications. Here we formulate a model for the emergence and spread of ideas which deals with this asymmetry by constraining the ability of agents to return to already abandoned concepts. The model exhibits a fairly regular pattern of global paradigm shifts, where older paradigms are eroded and subsequently replaced by new ones. The model sets the theme for a new class of pattern formation models, where local dynamics breaks the detailed balance in a way that prevents old states from defending themselves against new nucleating or invading states. The model allows for frozen events in terms of the coexistence of multiple metastable states. PMID:21405444

  9. A Paradigm for Spreadsheet Engineering Methodologies

    CERN Document Server

    Grossman, Thomas A

    2008-01-01

    Spreadsheet engineering methodologies are diverse and sometimes contradictory. It is difficult for spreadsheet developers to identify a spreadsheet engineering methodology that is appropriate for their class of spreadsheet, with its unique combination of goals, type of problem, and available time and resources. There is a lack of well-organized, proven methodologies with known costs and benefits for well-defined spreadsheet classes. It is difficult to compare and critically evaluate methodologies. We present a paradigm for organizing and interpreting spreadsheet engineering recommendations. It systematically addresses the myriad choices made when developing a spreadsheet, and explicitly considers resource constraints and other development parameters. This paradigm provides a framework for evaluation, comparison, and selection of methodologies, and a list of essential elements for developers or codifiers of new methodologies. This paradigm identifies gaps in our knowledge that merit further research.

  10. Phase transitions in paradigm shift models.

    Directory of Open Access Journals (Sweden)

    Huiseung Chae

    Full Text Available Two general models for paradigm shifts, deterministic propagation model (DM and stochastic propagation model (SM, are proposed to describe paradigm shifts and the adoption of new technological levels. By defining the order parameter m based on the diversity of ideas, Δ, it is studied when and how the phase transition or the disappearance of a dominant paradigm occurs as a cost C in DM or an innovation probability α in SM increases. In addition, we also investigate how the propagation processes affect the transition nature. From analytical calculations and numerical simulations m is shown to satisfy the scaling relation m=1-f(C/N for DM with the number of agents N. In contrast, m in SM scales as m=1-f(α(aN.

  11. A fat option for the pig: Hepatocytic differentiated mesenchymal stem cells for translational research

    Energy Technology Data Exchange (ETDEWEB)

    Brückner, Sandra, E-mail: sandra.brueckner@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); Tautenhahn, Hans-Michael, E-mail: hans-michael.tautenhahn@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); TRM, Translational Centre for Regenerative Medicine, Philipp-Rosenthal-Str. 55, Leipzig D-04103 (Germany); Winkler, Sandra, E-mail: sandra.pelz@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); Stock, Peggy, E-mail: peggy.stock@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); Dollinger, Matthias, E-mail: matthias.dollinger@uniklinik-ulm.de [University Hospital Ulm, First Department of Medicine, Albert-Einstein-Allee 23, Ulm D-89081 (Germany); Christ, Bruno, E-mail: bruno.christ@medizin.uni-leipzig.de [University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103 (Germany); TRM, Translational Centre for Regenerative Medicine, Philipp-Rosenthal-Str. 55, Leipzig D-04103 (Germany)

    2014-02-15

    Study background: Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Because of their anti-inflammatory and -apoptotic as well as pro-proliferative features, mesenchymal stem cells differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical translation of basic research requires pre-clinical approval in large animals. Therefore, we characterized porcine mesenchymal stem cells (MSC) from adipose tissue and bone marrow and their hepatocyte differentiation potential for future assessment of functional liver support after surgical intervention in the pig model. Methods: Mesenchymal surface antigens and multi-lineage differentiation potential of porcine MSC isolated by collagenase digestion either from bone marrow or adipose tissue (subcutaneous/visceral) were assessed by flow cytometry. Morphology and functional properties (urea-, glycogen synthesis and cytochrome P450 activity) were determined during culture under differentiation conditions and compared with primary porcine hepatocytes. Results: MSC from porcine adipose tissue and from bone marrow express the typical mesenchymal markers CD44, CD29, CD90 and CD105 but not haematopoietic markers. MSC from both sources displayed differentiation into the osteogenic as well as adipogenic lineage. After hepatocyte differentiation, expression of CD105 decreased significantly and cells adopted the typical polygonal morphology of hepatocytes. Glycogen storage was comparable in adipose tissue- and bone marrow-derived cells. Urea synthesis was about 35% lower in visceral than in subcutaneous adipose tissue-derived MSC. Cytochrome P450 activity increased significantly during differentiation and was twice as high in hepatocyte-like cells generated from bone marrow as from adipose tissue. Conclusion: The hepatocyte

  12. A fat option for the pig: Hepatocytic differentiated mesenchymal stem cells for translational research

    International Nuclear Information System (INIS)

    Study background: Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Because of their anti-inflammatory and -apoptotic as well as pro-proliferative features, mesenchymal stem cells differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical translation of basic research requires pre-clinical approval in large animals. Therefore, we characterized porcine mesenchymal stem cells (MSC) from adipose tissue and bone marrow and their hepatocyte differentiation potential for future assessment of functional liver support after surgical intervention in the pig model. Methods: Mesenchymal surface antigens and multi-lineage differentiation potential of porcine MSC isolated by collagenase digestion either from bone marrow or adipose tissue (subcutaneous/visceral) were assessed by flow cytometry. Morphology and functional properties (urea-, glycogen synthesis and cytochrome P450 activity) were determined during culture under differentiation conditions and compared with primary porcine hepatocytes. Results: MSC from porcine adipose tissue and from bone marrow express the typical mesenchymal markers CD44, CD29, CD90 and CD105 but not haematopoietic markers. MSC from both sources displayed differentiation into the osteogenic as well as adipogenic lineage. After hepatocyte differentiation, expression of CD105 decreased significantly and cells adopted the typical polygonal morphology of hepatocytes. Glycogen storage was comparable in adipose tissue- and bone marrow-derived cells. Urea synthesis was about 35% lower in visceral than in subcutaneous adipose tissue-derived MSC. Cytochrome P450 activity increased significantly during differentiation and was twice as high in hepatocyte-like cells generated from bone marrow as from adipose tissue. Conclusion: The hepatocyte

  13. Synthesis and characterization of aluminum and gallium complexes of heterocyclic thiosemicarbazones. crystal structures of Me2M[SC4H3CHNNC(S)SCH3] (M=Al, Ga)

    International Nuclear Information System (INIS)

    The synthesis and characterization of the monomeric group 13 heterocyclic thiosemicarbazone complexes Me2M[SC4H3CHNNC(S)SCH3] (M=Al (2), Ga (3)) are described. Compounds 2-3 were prepared using MMe3 (M=Al, Ga) in toluene with 2-thiophenecarboxaldehyde-S-methyldithiocarbazate under anaerobic conditions. These complexes have been characterized by 1H NMR, 13C NMR, elemental analyses, and single-crystal X-ray diffraction. 2 crystallizes in the monoclinic space group P21/c with unit cell parameters a=10.2930(5) A, b=18.564 (1) A, c=7.3812(6) A, V=1347.9(2) A3, Dcalc=1.342 gcm-3 for Z=4, 9281 reflections with Ibca with unit cell parameters a=13.340(3) A, b=19.9070(5) A, c=11.3690(2) A, V=2673.88(9) A3, Dcalc=1.511 gcm-3 for Z=8, 17004 reflections with I>3σ(I), R1=0.0480 and wR2=0.0524. Compound 3 is a monomeric gallium compound with a weak interaction between the pendant thiophene and the gallium center

  14. [Immunoregulatory role of mesenchymal stem cells in bone reparation processes].

    Science.gov (United States)

    Zubov, D O

    2008-01-01

    Bone marrow contains mesenchymal stem cells (MSC) including osteoblast progenitor cells. When culturedunder conditions promoting an osteoblastic phenotype,MSC proliferate to form colonies that produce alkaline phosphatase and, subsequently, a mature osteoblastic phenotype. Transplantation of cultured autologous MSC to patients with non-healing bone fractures gives a good result leading to complete bone fracture consolidation. The aim of the study is to determine a quantitative production of IL-1beta, IL-2, IL-4, IL-6, IL-8 and TNF-alpha by cultured uncommitted and committed osteogenic MSC. The results showed that the cytokine profile consisting of IL-1beta, IL-2, IL-4, IL-6, IL-8 and TNF-alpha is secreted by cultured MSC. The secretion of IL-1beta and IL-2 by cultured MSC together with hyper production of IL-6 (up to 276.5 pg/ml, pactivators of bone resorption, inflammation and some immunological reactions in the process of altered osteoreparation. PMID:18756772

  15. Role of mesenchymal stem cell-derived fibrinolytic factor in tissue regeneration and cancer progression.

    Science.gov (United States)

    Heissig, Beate; Dhahri, Douaa; Eiamboonsert, Salita; Salama, Yousef; Shimazu, Hiroshi; Munakata, Shinya; Hattori, Koichi

    2015-12-01

    Tissue regeneration during wound healing or cancer growth and progression depends on the establishment of a cellular microenvironment. Mesenchymal stem cells (MSC) are part of this cellular microenvironment, where they functionally modulate cell homing, angiogenesis, and immune modulation. MSC recruitment involves detachment of these cells from their niche, and finally MSC migration into their preferred niches; the wounded area, the tumor bed, and the BM, just to name a few. During this recruitment phase, focal proteolysis disrupts the extracellular matrix (ECM) architecture, breaks cell-matrix interactions with receptors, and integrins, and causes the release of bioactive fragments from ECM molecules. MSC produce a broad array of proteases, promoting remodeling of the surrounding ECM through proteolytic mechanisms. The fibrinolytic system, with its main player plasmin, plays a crucial role in cell migration, growth factor bioavailability, and the regulation of other protease systems during inflammation, tissue regeneration, and cancer. Key components of the fibrinolytic cascade, including the urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), are expressed in MSC. This review will introduce general functional properties of the fibrinolytic system, which go beyond its known function of fibrin clot dissolution (fibrinolysis). We will focus on the role of the fibrinolytic system for MSC biology, summarizing our current understanding of the role of the fibrinolytic system for MSC recruitment and the functional consequences for tissue regeneration and cancer. Aspects of MSC origin, maintenance, and the mechanisms by which these cells contribute to altered protease activity in the microenvironment under normal and pathological conditions will also be discussed.

  16. Addition of Adipose-Derived Stem Cells to Mesenchymal Stem Cell Sheets Improves Bone Formation at an Ectopic Site

    Directory of Open Access Journals (Sweden)

    Zhifa Wang

    2016-02-01

    Full Text Available To determine the effect of adipose-derived stem cells (ADSCs added to bone marrow-derived mesenchymal stem cell (MSC sheets on bone formation at an ectopic site. We isolated MSCs and ADSCs from the same rabbits. We then prepared MSC sheets for implantation with or without ADSCs subcutaneously in the backs of severe combined immunodeficiency (SCID mice. We assessed bone formation at eight weeks after implantation by micro-computed tomography and histological analysis. In osteogenic medium, MSCs grew to form multilayer sheets containing many calcium nodules. MSC sheets without ADSCs formed bone-like tissue; although neo-bone and cartilage-like tissues were sparse and unevenly distributed by eight weeks after implantation. In comparison, MSC sheets with ADSCs promoted better bone regeneration as evidenced by the greater density of bone, increased mineral deposition, obvious formation of blood vessels, large number of interconnected ossified trabeculae and woven bone structures, and greater bone volume/total volume within the composite constructs. Our results indicate that although sheets of only MSCs have the potential to form tissue engineered bone at an ectopic site, the addition of ADSCs can significantly increase the osteogenic potential of MSC sheets. Thus, the combination of MSC sheets with ADSCs may be regarded as a promising therapeutic strategy to stimulate bone regeneration.

  17. Comparison of human sodium iodide symporter (hNIS) gene expression between lentiviral and adenoviral vectors in rat mesenchymal stem cell

    International Nuclear Information System (INIS)

    Quantitative comparison of transgene expression within stem cells between lentivirus and adenovirus-mediated delivery systems has not been done. Here, we evaluated the human sodium iodide symporter (hNIS) gene expression in rat mesenchymal stem cell (rMSC) transduced by lentivirus or adenovirus, and compared the hNIS expression quantitatively between the two delivery systems. Lentiviral-mediated stably hNIS expressing rMSC (lenti-hNIS-rMSC) was constructed by cloning the hNIS gene into pLenti6/UbC/V5-DEST (Invitrogen) to obtain pLenti-hNIS, transducing rMSC with the pLenti-hNIS, and selecting with blasticidin for 3 weeks. Recombinant adenovirus expressing hNIS gene (Rad-hNIS) was produced by homologous recombination and Rad-hNIS transduced rMSC (adeno-hNIS-rMSC) was evaluated for the hNIS expression 48 hours post infection at MOI 1, 5, 20, 50, and 100. The hNIS expression in lenti-hNIS-rMSC or adeno-hNIS-rMSC was assessed by immunocytochemistry, western blot, and I-125 uptake. Immunocytochemistry using mono-clonal anti-hNIS antibody revealed that intensity of hNIS immunoreactivity in lenti-hNIS-rMSC was greater than that in adeno-hNIS-rMSC at MOl 20 but lower than that at MOl 50. Western blot analysis also showed that lenti-hNIS-rMSC was intermediate between adeno-hNIS-rMSCs at MOl 20 and 50 in hNIS expression. However in vitro I-125 uptake test demonstrated that iodide uptake in lenti-hNIS-rMSC (297046659 picomole/106 cells) was greater than that in adeno-hNIS-rMSC at MOI 100 (61682134 picomole/106 cells). These results suggest that lentivirus mediated hNIS expression is greater in terms of hNIS function but lower in terms of hNIS protein amount than adenovirus mediated hNIS expression 48 hours post infection. Stem cell tracking using hNIS as a reporter gene should be conducted in consideration of relative viral efficiency of transgene expression

  18. Response to intravenous allogeneic equine cord-blood-derived mesenchymal stromal cells administered from chilled or frozen state in serum and protein free media

    Directory of Open Access Journals (Sweden)

    Lynn Brandon Williams

    2016-07-01

    Full Text Available Equine Mesenchymal stromal cells (MSC are commonly transported, chilled or frozen, to veterinary clinics. These MSC must remain viable and minimally affected by culture, transport, or injection processes. The safety of two carrier solutions developed for optimal viability and excipient use were evaluated in ponies, with and without allogeneic cord blood-derived (CB MSC. We hypothesized that neither the carrier solutions nor CB-MSC would elicit measurable changes in clinical, hematological, or biochemical parameters. In 9 ponies (study 1 a bolus of HypoThermosol® FRS (HTS-FRS, CryoStor® CS10 (CS10 or saline was injected IV (n=3/treatment. Study 2, following a one week washout period 5x107 pooled allogeneic CB-MSC were administered IV in HTS-FRS following 24h simulated chilled transport. Study 3, following another one week washout period 5x107 pooled allogeneic CB-MSC were administered IV in CS10 immediately after thawing. Nine ponies received CB-MSCs in study 2 and 3 and three ponies received the cell carrier media without cells. CB-MSCs were pooled in equal numbers from five unrelated donors. In all studies ponies were monitored with physical examination, and blood collection for 7 days following injection. CD4 and CD8 lymphocyte populations were also evaluated in each blood sample.In all three studies, physical exam, complete blood cell count, serum biochemistry, and coagulation panel did not deviate from established normal ranges. Proportions of CD4+ and CD8+ lymphocytes increased at 168h post injection in CB-MSC treatment groups regardless of the carrier solution. Decreases in CD4+/CD8+ double positive populations were observed at 24 h and 72 h in CB-MSC treated animals. There was no difference in viability between CB-MSC suspended in HTS-FRS or CS10.HTS-FRS and CS10 used for low volume excipient injection of MSC suspensions was not associated with short-term adverse reactions. HTS-FRS and CS10 both adequately maintain CB-MSC viability

  19. Multiple intravenous infusions of bone marrow mesenchymal stem cells reverse hyperglycemia in experimental type 2 diabetes rats.

    Science.gov (United States)

    Hao, Haojie; Liu, Jiejie; Shen, Jing; Zhao, Yali; Liu, Huilin; Hou, Qian; Tong, Chuan; Ti, Dongdong; Dong, Liang; Cheng, Yu; Mu, Yiming; Liu, Jianping; Fu, Xiaobing; Han, Weidong

    2013-07-01

    The worldwide rapid increase in diabetes poses a significant challenge to current therapeutic approaches. Single-dose mesenchymal stem cell (MSC) infusion ameliorates hyperglycemia but fails to restore normoglycemia in diabetic animals. We therefore hypothesized that multiple intravenous MSC infusions may reverse hyperglycemia in type 2 diabetes (T2D) rats. We administered serial allogenous bone-marrow derived MSC infusions (1 × 10(6)cells/infusion) via the tail vein once every 2 weeks to T2D rats, induced by high-fat diet and streptozocin (STZ) administration. Hyperglycemia decreased only transiently after a single infusion in early-phase (1 week) T2D rats, but approximated normal levels after at least three-time infusions. This normal blood level was maintained for at least 9 weeks. Serum concentrations of both insulin and C-peptide were dramatically increased after serial MSC infusions. Oral glucose tolerance tests revealed that glucose metabolism was significantly ameliorated. Immunofluorescence analysis of insulin/glucagon staining revealed the restoration of islet structure and number after multiple MSC treatments. When multiple-MSC treatment was initiated in late-phase (5 week) T2D rats, the results were slightly different. The results of this study suggested that a multiple-MSC infusion strategy offers a viable clinical option for T2D patients.

  20. Collagen Promotes Higher Adhesion, Survival and Proliferation of Mesenchymal Stem Cells.

    Directory of Open Access Journals (Sweden)

    Chinnapaka Somaiah

    Full Text Available Mesenchymal stem cells (MSC can differentiate into several cell types and are desirable candidates for cell therapy and tissue engineering. However, due to poor cell survival, proliferation and differentiation in the patient, the therapy outcomes have not been satisfactory. Although several studies have been done to understand the conditions that promote proliferation, differentiation and migration of MSC in vitro and in vivo, still there is no clear understanding on the effect of non-cellular bio molecules. Of the many factors that influence the cell behavior, the immediate cell microenvironment plays a major role. In this context, we studied the effect of extracellular matrix (ECM proteins in controlling cell survival, proliferation, migration and directed MSC differentiation. We found that collagen promoted cell proliferation, cell survival under stress and promoted high cell adhesion to the cell culture surface. Increased osteogenic differentiation accompanied by high active RHOA (Ras homology gene family member A levels was exhibited by MSC cultured on collagen. In conclusion, our study shows that collagen will be a suitable matrix for large scale production of MSC with high survival rate and to obtain high osteogenic differentiation for therapy.

  1. Reinforcing the Afrocentric Paradigm: A Theoretical Project

    Science.gov (United States)

    Sams, Timothy E.

    2010-01-01

    Thomas Kuhn's 1962 groundbreaking work, "The Scientific Revolution," established the process for creating, and the components of, a disciplinary paradigm. This "scientific revolution" has evolved to become the standard for determining a field's claim to disciplinary status. In 2001 and 2003, Ama Mazama, used Kuhn's model to establish the…

  2. A Review of Process Modeling Language Paradigms

    Institute of Scientific and Technical Information of China (English)

    MA Qin-hai; GUAN Zhi-min; LI Ying; ZHAO Xi-nan

    2002-01-01

    Process representation or modeling plays an important role in business process engineering.Process modeling languages can be evaluated by the extent to which they provide constructs useful for representing and reasoning about the aspects of a process, and subsequently are chosen for a certain purpose.This paper reviews process modeling language paradigms and points out their advantages and disadvantages.

  3. Toward an Ecological Paradigm in Adventure Programming

    Science.gov (United States)

    Beringer, Almut

    2004-01-01

    Many forms of adventure therapy, in particular wilderness therapy, rely on challenges in the outdoors to achieve objectives of client change. While nature is drawn on as a medium for therapy and healing, some adventure therapists give nature little if any mention when it comes to explaining therapeutic success. The dominant paradigm in psychology…

  4. Augmenting the ADDIE Paradigm for Instructional Design

    Science.gov (United States)

    Ni, Xiaopeng; Branch, Robert Maribe

    2008-01-01

    The authors discuss topics appropriate for augmenting the ADDIE paradigm for instructional design. The topics selected are based on data from a study of working professionals who successfully completed an instructional design and technology certificate program and who identified related topics that they regarded as beneficial. The participants…

  5. New Paradigms for Computer Aids to Invention.

    Science.gov (United States)

    Langston, M. Diane

    Many people are interested in computer aids to rhetorical invention and want to know how to evaluate an invention aid, what the criteria are for a good one, and how to assess the trade-offs involved in buying one product or another. The frame of reference for this evaluation is an "old paradigm," which treats the computer as if it were paper, but…

  6. Empirical Testing of an Affective Learning Paradigm.

    Science.gov (United States)

    Asmus, Edward P., Jr.

    1980-01-01

    This investigation of a college music course examined the effectiveness of a cyclical affective learning paradigm based on the premise that student affect toward a course of instruction will dictate, in part, cognitive performance. Results suggest that teachers would be better advised to concentrate on cognitive instruction than on affect.…

  7. Haptics in computer music : a paradigm shift

    CERN Document Server

    Castagné, Nicolas; Florens, Jean-Loup; Luciani, Annie

    2010-01-01

    With an historical point of view combined with a bibliographic overview, the article discusses the idea that haptic force feedback transducers correspond with a paradigm shift in our real-time tools for creating music. So doing, il shows that computer music may be regarded as a major field of research and application for haptics.

  8. Has the Education Paradigm Begun to Shift?

    Science.gov (United States)

    Chadwick, Clifton B.

    2014-01-01

    The author reviews various elements of what may be considered as evidence that the long-awaited shift in the education paradigm is actually happening. Concepts like student-centered learning, attainment-based evaluation, knowledge-based constructivism, and effort-based intelligence are growing, are being more widely recognized as important, and…

  9. Production planning development and paradigm integration

    Directory of Open Access Journals (Sweden)

    Galina Ledneva

    2009-12-01

    Full Text Available The paper reviews principles of different concepts of enterprise management including a theory of constrains, a Balanced Scorecard, lean production, Six Sigma. The authors believe that creating some mix or integration of these paradigms can bring extraordinary effect for production management. As example the modified Balanced Scorecard based on constraints and its application on Magnitorsk metallurgical enterprise in Russia is described.

  10. Operationalizing Social Justice Counseling: Paradigm to Practice

    Science.gov (United States)

    Lewis, Judith A.

    2011-01-01

    Social justice counseling, like all humanistic models, recognizes the dignity of each human being, affirms the right of all people to choose and work toward their own goals, and asserts the importance of service to community. The social justice paradigm brings a special emphasis on the role of the environment. (Contains 1 figure and 1 table.)

  11. A new paradigm for doing Reformed dogmatics

    Directory of Open Access Journals (Sweden)

    G. J. Spykman

    1992-06-01

    Full Text Available When discussing Reformational Theology: A New Paradigm for Doing Dogmatics some people may call it my opus magnum. Perhaps time 'will tell. The book has only recently - early 1992 - entered the marketplace of theological ideas. How critic readers and reviewers respond will go a long way toward settling the case.

  12. Den postmoderna stadens två paradigm

    DEFF Research Database (Denmark)

    Nielsen, Tom

    2005-01-01

    the attention of politicians, planners and architects today is focused on the individual, not the collective. But the policy of the third way has no counterpart in an urbanism torn between two paradigms. Tom Nielsen paints the picture of what has to urban development since the welfare state...

  13. ACCOUNTING PARADIGMS WHICH FAVOR HISTORICAL COST

    OpenAIRE

    Valentin Gabriel CRISTEA

    2014-01-01

    Henning Kirkegaard shows that the evolution of accounting is to shift from one paradigm to another . Business continuity perspective should guide the company into the future , without confine it exclusively in the past. Accounting in its classical form , however, can not be dissociated from the historical cost evaluation .

  14. 06472 Abstracts Collection - XQuery Implementation Paradigms

    NARCIS (Netherlands)

    Boncz, Peter A.; Grust, Torsten; Siméon, Jerome; Keulen, van Maurice; Boncz, P.A.; Grust, T.; Siméon, J.; Keulen, van M.

    2007-01-01

    From 19.11.2006 to 22.11.2006, the Dagstuhl Seminar 06472 ``XQuery Implementation Paradigms'' was held in the International Conference and Research Center (IBFI), Schloss Dagstuhl. During the seminar, several participants presented their current research, and ongoing work and open problems were disc

  15. 06472 Abstracts Collection - XQuery Implementation Paradigms

    NARCIS (Netherlands)

    Boncz, P.A.; Grust, T.; Siméon, J.; Keulen, M. van

    2007-01-01

    From 19.11.2006 to 22.11.2006, the Dagstuhl Seminar 06472 "XQuery Implementation Paradigms" was held in the International Conference and Research Center (IBFI), Schloss Dagstuhl. During the seminar, several participants presented their current research, and ongoing work and open problems were discus

  16. Redesigning Higher Education: Embracing a New Paradigm

    Science.gov (United States)

    Watson, William R.; Watson, Sunnie Lee

    2014-01-01

    Higher education is under enormous pressure to transform itself and embrace a new paradigm. Operating under an outdated model that no longer aligns with the realities of modern society, institutions of higher education are recognizing the need to drastically remake themselves or possibly cease to exist. This article explores the current landscape…

  17. Dark matter and the neutrino portal paradigm

    CERN Document Server

    González-Macías, Vannia; Wudka, José

    2016-01-01

    A simple extension of the Standard Model (SM) that provides an explicit realization of the dark-matter (DM) neutrino-portal paradigm is presented. The leading interactions between the dark sector, containing scalars and relic fermions, and the SM involve neutrinos. This model meets all observational constraints.

  18. ACCOUNTING PARADIGMS WHICH FAVOR HISTORICAL COST

    Directory of Open Access Journals (Sweden)

    Valentin Gabriel CRISTEA

    2014-05-01

    Full Text Available Henning Kirkegaard shows that the evolution of accounting is to shift from one paradigm to another . Business continuity perspective should guide the company into the future , without confine it exclusively in the past. Accounting in its classical form , however, can not be dissociated from the historical cost evaluation .

  19. Towards personalized regenerative cell therapy

    DEFF Research Database (Denmark)

    Lin, Lin; Bolund, Lars; Luo, Yonglun

    2015-01-01

    Mesenchymal stem cells (MSCs) are adult stem cells with the capacity of self-renewal and multilineage differentiation, and can be isolated from several adult tissues. However, isolating MSCs from adult tissues for cell therapy is hampered by the invasive procedure, the rarity of the cells...... and their attenuated proliferation capacity when cultivated and expanded in vitro. Human MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have now evolved as a promising alternative cell source for MSCs and regenerative medicine. Several groups, including ours, have reported successful derivation...... of functional iPSC-MSCs and applied these cells in MSC-based therapeutic testing. Still, the current experience and understanding of iPSC-MSCs with respect to production methods, safety and efficacy are primitive. In this review, we highlight the methodological progress in iPSC-MSC research, describing...

  20. Mesenchymal stem cells for clinical application.

    Science.gov (United States)

    Sensebé, L; Krampera, M; Schrezenmeier, H; Bourin, P; Giordano, R

    2010-02-01

    Mesenchymal Stem Cells/Multipotent Marrow Stromal Cells (MSC) are multipotent adult stem cells present in all tissues, as part of the perivascular population. As multipotent cells, MSCs can differentiate into different tissues originating from mesoderm ranging from bone and cartilage, to cardiac muscle. Conflicting data show that MSCs could be pluripotent and able to differentiate into tissues and cells of non-mesodermic origin as neurons or epithelial cells. Moreover, MSCs exhibit non-HLA restricted immunosuppressive properties. This wide range of properties leads to increasing uses of MSC for immunomodulation or tissue repair. Based on their immunosuppressive properties MSC are used particularly in the treatment of graft versus host disease, For tissue repair, MSCs can work by different ways from cell replacement to paracrine effects through the release of cytokines and to regulation of immune/inflammatory responses. In regenerative medicine, trials are in progress or planed for healing/repair of different tissue or organs as bone, cartilage, vessels, myocardium, or epithelia. Although it has been demonstrated that ex-vivo expansion processes using fetal bovine serum, recombinant growth factors (e.g. FGF2) or platelet lysate are feasible, definitive standards to produce clinical-grade MSC are still lacking. MSCs have to be produced according GMP and regulation constraints. For answering to the numerous challenges in this fast developing field of biology and medicine, integrative networks linking together research teams, cell therapy laboratories and clinical teams are needed.