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Sample records for autologous mesenchymal stem

  1. Importance of mesenchymal stem cells in autologous fat grafting

    DEFF Research Database (Denmark)

    Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter Viktor

    2012-01-01

    Autologous fat grafting (lipofilling) enables repair and augmentation of soft tissues and is increasingly used both in aesthetic and reconstructive surgery. Autologous fat has several advantages, including biocompatibility, versatility, natural appearance, and low donor site morbidity. The main...... the fat graft with adipose tissue-derived mesenchymal stem cells (ASC) before transplantation. We have reviewed original studies published on fat transplantation enriched with ASC. We found four murine and three human studies that investigated the subject after a sensitive search of publications...... limitation is unpredictable graft resorption, which ranges from 25%-80%, probably as a result of ischaemia and lack of neoangiogenesis. To obviate these disadvantages, several studies have searched for new ways of increasing the viability of the transplanted tissue. One promising approach has been to enrich...

  2. A Biological Pacemaker Restored by Autologous Transplantation of Bone Marrow Mesenchymal Stem Cells

    Institute of Scientific and Technical Information of China (English)

    REN Xiao-qing; PU Jie-lin; ZHANG Shu; MENG Liang; WANG Fang-zheng

    2008-01-01

    Objective:To restore cardiac autonomic pace function by autologous transplantation and committed differentiation of bone marrow mesenchymal stem cells, and explore the technique for the treatment of sick sinus syndrome. Methods:Mesenchymal stem cells isolated from canine bone marrow were culture-expanded and differentiated in vitro by 5-azacytidine. The models of sick sinus syndrome in canines were established by ablating sinus node with radio-frequency technique. Differentiated mesenchymal stem cells labeled by BrdU were autologously transplanted into sinus node area through direct injection. The effects of autologous transplantation of mesenchymal stem cells on cardiac autonomic pace function in sick sinus syndrome models were evaluated by electrocardiography, pathologic and immunohistochemical staining technique.Results:There was distinct improvement on pace function of sick sinus syndrome animal models while differentiated mesenchymal stem cells were auto-transplanted into sinus node area. Mesenchymal stem cells transplanted in sinus node area were differentiated into similar sinus node cells and endothelial cells in vivo, and established gap junction with native cardiomyocytes. Conclusion:The committed-induced mesenchymal stem cells transplanted into sinus node area can differentiate into analogous sinus node cells and improve pace function in canine sick sinus syndrome models.

  3. Transplantation of autologous bone marrow-derived mesenchymal stem cells for traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Jindou Jiang; Xingyao Bu; Meng Liu; Peixun Cheng

    2012-01-01

    Results from the present study demonstrated that transplantation of autologous bone marrow-derived mesenchymal stem cells into the lesion site in rat brain significantly ameliorated brain tissue pathological changes and brain edema, attenuated glial cell proliferation, and increased brain-derived neurotrophic factor expression. In addition, the number of cells double-labeled for 5-bromodeoxyuridine/glial fibrillary acidic protein and cells expressing nestin increased. Finally, blood vessels were newly generated, and the rats exhibited improved motor and cognitive functions. These results suggested that transplantation of autologous bone marrow-derived mesenchymal stem cells promoted brain remodeling and improved neurological functions following traumatic brain injury.

  4. Autologous mesenchymal stem cells transplantation in adriamycin-induced cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jing; LI Geng-shan; LI Guo-cao; ZHOU Qing; LI Wen-qiang; XU Hong-xin

    2005-01-01

    @@ Recent studies have suggested benefits of mesenchymal stem cells (MSCs) transplantation for the regeneration of cardiac tissue and function improvement of regionally infracted myocardium, but its effects on global heart failure is still little known. This study suggested the capacity of MSCs to transdifferentiate to cardiac cells in a nonischemic cardiomyopathic setting, and the effect of the cells on heart function.

  5. Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats

    OpenAIRE

    Arzi, Boaz; Mills-Ko, Emily; Frank J.M. Verstraete; Kol, Amir; Walker, Naomi J.; Badgley, Megan R.; Fazel, Nasim; William J. Murphy; Vapniarsky, Natalia; Borjesson, Dori L.

    2015-01-01

    Mesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous AS...

  6. The Use of Autologous Mesenchymal Stem Cells for Cell Therapy of Patients with Amyotrophic Lateral Sclerosis in Belarus.

    Science.gov (United States)

    Rushkevich, Yu N; Kosmacheva, S M; Zabrodets, G V; Ignatenko, S I; Goncharova, N V; Severin, I N; Likhachev, S A; Potapnev, M P

    2015-08-01

    We studied a new method of treatment of amyotrophic lateral sclerosis with autologous mesenchymal stem cells. Autologous mesenchymal stem cells were injected intravenously (intact cells) or via lumbar puncture (cells committed to neuronal differentiation). Evaluation of the results of cell therapy after 12-month follow-up revealed slowing down of the disease progression in 10 patients in comparison with the control group consisting of 15 patients. The cell therapy was safe for the patients.

  7. Autologous serum can induce mesenchymal stem cells into hepatocyte-like cells

    Institute of Scientific and Technical Information of China (English)

    Yang Yi; Huo Jianhua; Qu Bo; Wu Shenli; Zhang Mingyu; Wang Zuoren

    2008-01-01

    Objective: To investigate whether the rabbit serum after radiofrequency ablation to liver tumor can induce mesenchymal stem cells (MSCs) differentiating into hepatocyte-like cells in order to find a new source and culture process for repairing liver injury. Methods: A tumor piece of 1 mm×1 mm×1 mm was transplanted into a tunnel at right liver of rabbits. The model of liver tumor was established after 2-3 weeks. The serum was collected from rabbits 72 h after being subjected to radiofrequency ablation of the liver tumor. Mesenchymal stem cells were isolated from rabbit bone marrow and cultured in DMEM containing autologous rabbit serum. Three kinds of media (L-DMEM) were tested respectively: ① containing 10% fetal calf serum (FCS);② containing 30% rabbit autologous serum after radiofrequency ablation of the liver tumor (ASRF); ③ containing 30% rabbit autologous serum (AS). MSCs were cultured on 12-well plates until passage 2 and examined under the light and electron microscopy at indicted intervals. The expression of albumin and CK18 was detected using immunofluorescence to identify the characteristics of differentiated cells. Results: MSCs performed differently in the presence of fetal calf serum, rabbit autologous serum and rabbit autologous serum after radiofrequency ablation of the liver tumor. Induced by the serum after radiofrequency ablation to liver tumor for 7 d, the spindle-shaped MSCs turned into round shaped and resembled hepatocyte-like cells. The reactions were not found in MSCs cultured in FCS and AS groups. After induction for 14 d, slender microvilli, cell-cell junction structure and cholangiole emerged, and the differentiated cells expressed albumin and CK18. All those could not been observed in 10% FCS and 30% autologous serum groups. Conclusion: Mesenchymal stem cells differentiate into hepatocyte-like cells in the serum after radiofrequency ablation of liver tumor, providing us a potential cell source and culture process for clinical

  8. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Puente, Pilar de la, E-mail: pilardelapuentegarcia@gmail.com [Tissue Bank, San Francisco Clinic Foundation, Av./Facultad 51, 5°, 24004 León (Spain); Ludeña, Dolores [Pathology Service, University Hospital of Salamanca, P/San Vicente 58-182, 37007 Salamanca (Spain); López, Marta; Ramos, Jennifer; Iglesias, Javier [Tissue Bank, San Francisco Clinic Foundation, Av./Facultad 51, 5°, 24004 León (Spain)

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  9. Comparison Between Transepicardial Cell Transplantations: Autologous Undifferentiated Versus Differentiated Marrow Mesenchymal Stem Cells

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    Farid Azmoudeh Ardalan

    2007-06-01

    Full Text Available Background: Marrow-derived mesenchymal stem cells (MSCs have been heralded as a source of great promise for the regeneration of the infarcted heart. There are no clear data as to whether or not in vitro differentiation of MSCs into major myocardial cells can increase the beneficial effects of MSCs. The aim of this study was to address this issue.Methods: To induce MSCs to transdifferentiate into cardiomyocytes and endothelial cells, 5-Azacytidine and vascular endothelial growth factor (VEGF were used, respectively. Myocardial infarction in rabbits was generated by ligating the left anterior descending coronary artery. The animals were divided into three experimental groups: I control group, II undifferentiated mesenchymal stem cell transplantation group, and III differentiated mesenchymal stem cell transplantation group. The three groups received peri-infarct injections of culture media, autologous undifferentiated MSCs, and autologous differentiated MSCs, respectively. Echocardiography and pathology were performed in order to search for improvement in the cardiac function and reduction in the infarct size. Results: Improvements in the left ventricular function and reductions in the infarcted area were observed in both cell transplanted groups (Groups II and III to the same degree. Conclusions: There is no need for prior differentiation induction of marrow-derived MSCs before transplantation, and peri-infarct implantation of MSCs can effectively reduce the size of the infarct and improve the cardiac function.

  10. Autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia

    Institute of Scientific and Technical Information of China (English)

    Lu Debin; Jiang Youzhao; Liang Ziwen; Li Xiaoyan; Zhang Zhonghui; Chen Bing

    2008-01-01

    Objective: To study the efficacy and safety of autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Methods: Fifty Type 2 diabetic patients with lower limb ischemia were enrolled and randomized to either transplanted group or control group. Patients in both group received the same conventional treatment. Meanwhile, 20 ml bone marrow from each transplanted patient were collected, and the mesenchymal stem cells were separated by density gradient centrifugation and cultured in the medium with autologous serum. After three-weeks adherent culture in vitro, 7.32×108-5.61×109 mesenchymal stern cells were harvested and transplanted by multiple intramuscular and hypodermic injections into the impaired lower limbs. Results: At the end of 12-week follow-up, 5 patients were excluded from this study because of clinical worsening or failure of cell culture. Main ischemic symptoms, including rest pain and intermittent claudication, were improved significantly in transplanted patients. The ulcer healing rate of the transplanted group (15 of 18, 83.33%) was significantly higher than that of the control group (9 of 20, 45.00%, P=0.012).The mean of resting ankle-brachial index (ABI) in transplanted group significantly was increased from 0.61±0.09 to 0.74±0.11 (P<0.001). Magnetic resonance angiography (MRA) demonstrated that there were more patients whose score of new vessels exceeded or equaled to 2 in the transplant patients (11 of 15) than in control patients (2 of 14, P=0.001). Lower limb amputation rate was significantly lower in transplanted group than in the control group (P=0.040). No adverse effects was observed in transplanted group. Conclusion: These results indicate that the autologous transplantation of bone marrow mesenehymal stem cells relieves critical lower limb ischemia and promotes ulcers healing in Type 2 diabetic patients.

  11. Autologous adipose tissue-derived mesenchymal stem cells are involved in rat liver regeneration following repeat partial hepatectomy

    OpenAIRE

    Liu, Tao; MU, HONG; Shen, Zhongyang; SONG, ZHUOLUN; Chen, Xiaobo; Wang, Yuliang

    2016-01-01

    Adipose tissue-derived mesenchymal stem cells (ADSCs) have been considered to be attractive and readily available adult mesenchymal stem cells, and they are becoming increasingly popular for use in regenerative cell therapy, as they are readily accessible through minimally invasive techniques. The present study investigated whether autologous ADSC transplantation promoted liver regeneration following a repeat partial hepatectomy in rats. The rats were divided into three groups as follows: 70%...

  12. Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence

    Science.gov (United States)

    Perrot, Pierre; Rousseau, Julie; Bouffaut, Anne-Laure; Rédini, Françoise; Cassagnau, Elisabeth; Deschaseaux, Frédéric; Heymann, Marie-Françoise; Heymann, Dominique; Duteille, Franck; Trichet, Valérie; Gouin, François

    2010-01-01

    Background Osteosarcoma is the most common malignant primary bone tumour in young adult treated by neo adjuvant chemotherapy, surgical tumor removal and adjuvant multidrug chemotherapy. For correction of soft tissue defect consecutive to surgery and/or tumor treatment, autologous fat graft has been proposed in plastic and reconstructive surgery. Principal Findings We report here a case of a late local recurrence of osteosarcoma which occurred 13 years after the initial pathology and 18 months after a lipofilling procedure. Because such recurrence was highly unexpected, we investigated the possible relationship of tumor growth with fat injections and with mesenchymal stem/stromal cell like cells which are largely found in fatty tissue. Results obtained in osteosarcoma pre-clinical models show that fat grafts or progenitor cells promoted tumor growth. Significance These observations and results raise the question of whether autologous fat grafting is a safe reconstructive procedure in a known post neoplasic context. PMID:20544017

  13. Bone marrow concentrate for autologous transplantation in minipigs. Characterization and osteogenic potential of mesenchymal stem cells.

    Science.gov (United States)

    Herten, M; Grassmann, J P; Sager, M; Benga, L; Fischer, J C; Jäger, M; Betsch, M; Wild, M; Hakimi, M; Jungbluth, P

    2013-01-01

    Autologous bone marrow plays an increasing role in the treatment of bone, cartilage and tendon healing disorders. Cell-based therapies display promising results in the support of local regeneration, especially therapies using intra-operative one-step treatments with autologous progenitor cells. In the present study, bone marrow-derived cells were concentrated in a point-of-care device and investigated for their mesenchymal stem cell (MSC) characteristics and their osteogenic potential. Bone marrow was harvested from the iliac crest of 16 minipigs. The mononucleated cells (MNC) were concentrated by gradient density centrifugation, cultivated, characterized by flow cytometry and stimulated into osteoblasts, adipocytes, and chondrocytes. Cell differentiation was investigated by histological and immunohistological staining of relevant lineage markers. The proliferation capacity was determined via colony forming units of fibroblast and of osteogenic alkaline-phosphatase-positive-cells. The MNC could be enriched 3.5-fold in nucleated cell concentrate in comparison to bone marrow. Flow cytometry analysis revealed a positive signal for the MSC markers. Cells could be differentiated into the three lines confirming the MSC character. The cellular osteogenic potential correlated significantly with the percentage of newly formed bone in vivo in a porcine metaphyseal long-bone defect model. This study demonstrates that bone marrow concentrate from minipigs display cells with MSC character and their osteogenic differentiation potential can be used for osseous defect repair in autologous transplantations.

  14. Platelet-rich plasma-induced bone marrow mesenchymal stem cells versus autologous nerve grafting for sciatic nerve repair

    Institute of Scientific and Technical Information of China (English)

    Changsuo Xia; Yajuan Li; Wen Cao; Zhaohua Yu

    2010-01-01

    Autologous nerve grafting is the gold standard of peripheral nerve repair.We previously showed that autologous platelet-rich plasma(PRP)contains high concentrations of growth factors and can induce in vitro cultured bone marrow mesenchymal stem cells(BMSCs)to differentiate into Schwann cells.Here we used PRP-induced BMSCs combined with chemically extracted acellular nerves to repair sciatic nerve defects and compared the effect with autologous nerve grafting.The BMSCs and chemically extracted acellular nerve promoted target muscle wet weight restoration,motor nerve conduction velocity,and axonal and myelin sheath regeneration,with similar effectiveness to autologous nerve grafting.This finding suggests that PRP induced BMSCs can be used to repair peripheral nerve defects.

  15. Reconstruction of beagle hemi-mandibular defects with allogenic mandibular scaffolds and autologous mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    ChangKui Liu

    Full Text Available Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs can increase the integration of massive allografts (hemi-mandible in a large animal model.Thirty beagle dogs received surgical left-sided hemi-mandibular defects, and then divided into two equal groups. Bony defects of the control group were reconstructed using allografts only. Those of the experimental group were reconstructed using allogenic mandibular scaffold-loaded autologous MSCs. Beagles from each group were killed at 4 (n = 4, 12 (n = 4, 24 (n = 4 or 48 weeks (n = 3 postoperatively. CT and micro-CT scans, histological analyses and the bone mineral density (BMD of transplants were used to evaluate defect reconstruction outcomes.Gross and CT examinations showed that the autologous bone grafts had healed in both groups. At 48 weeks, the allogenic mandibular scaffolds of the experimental group had been completely replaced by new bone, which has a smaller surface area to that of the original allogenic scaffold, whereas the scaffold in control dogs remained the same size as the original allogenic scaffold throughout. At 12 weeks, the BMD of the experimental group was significantly higher than the control group (p<0.05, and all micro-architectural parameters were significantly different between groups (p<0.05. Histological analyses showed almost all transplanted allogeneic bone was replaced by new bone, principally fibrous ossification, in the experimental group, which differed from the control group where little new bone formed.Our study demonstrated the feasibility of MSC-loaded allogenic mandibular scaffolds for the reconstruction of hemi-mandibular defects. Further studies are needed to test whether these results can be surpassed by the use of allogenic mandibular scaffolds loaded with a combination of MSCs and osteoinductive growth

  16. Effect of autologous bone mesenchymal stem cell transplantation on neurological function in rehabilitation period of multifocal cerebral hemorrhage

    Institute of Scientific and Technical Information of China (English)

    Rui Zhang

    2016-01-01

    Objective:To study the effect of autologous bone mesenchymal stem cell transplantation on neurological function in rehabilitation period of multifocal cerebral hemorrhage.Methods:A total of 48 patients with multifocal cerebral hemorrhage who were treated in our hospital from April 2012 to December 2014 were selected as the research subjects, the therapy was made according to the illness and the patients’ will, combined treatment group received minimally invasive evacuation of hematoma combined with autologous bone mesenchymal stem cell transplantation therapy, surgical treatment group received regular minimally invasive evacuation of hematoma, and then imaging features, endothelial progenitor cell activation in peripheral blood as well as the content of nerve injury molecules and neurotrophic factors in serum of two groups were compared.Results:According to the result of head CT scan, the degree of brain edema of both groups was reduced 14 days after treatment, and the reducing degree of brain edema of combined treatment group was more significant than that of surgical treatment group; the 7th day, 14th day, 21st day and 28th day after treatment, CD34+CD133+endothelial progenitor cell levels in peripheral blood of combined treatment group were higher than those of surgical treatment group; 7th day and 14th day after treatment, serum S100β and NSE levels of combined treatment group were significantly lower than those of surgical treatment group; 21st day and 28th day after treatment, serum BDNF and NGF levels of combined treatment group were significantly higher than those of surgical treatment group. Conclusions:Autologous bone mesenchymal stem cell transplantation can relieve cerebral edema, increase the content of endothelial progenitor cells and neurotrophic factors and decrease neurological function injury in patients with multifocal cerebral hemorrhage, and it is conducive to the recovery of neurological function in patients with cerebral hemorrhage.

  17. Scaffold-based delivery of autologous mesenchymal stem cells for mandibular distraction osteogenesis: preliminary studies in a porcine model.

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    Zongyang Sun

    Full Text Available PURPOSE: Bone regeneration through distraction osteogenesis (DO is promising but remarkably slow. To accelerate it, autologous mesenchymal stem cells have been directly injected to the distraction site in a few recent studies. Compared to direct injection, a scaffold-based method can provide earlier cell delivery with potentially better controlled cell distribution and retention. This pilot project investigated a scaffold-based cell-delivery approach in a porcine mandibular DO model. MATERIALS AND METHODS: Eleven adolescent domestic pigs were used for two major sets of studies. The in-vitro set established methodologies to: aspirate bone marrow from the tibia; isolate, characterize and expand bone marrow-derived mesenchymal stem cells (BM-MSCs; enhance BM-MSC osteogenic differentiation using FGF-2; and confirm cell integration with a gelatin-based Gelfoam scaffold. The in-vivo set transplanted autologous stem cells into the mandibular distraction sites using Gelfoam scaffolds; completed a standard DO-course and assessed bone regeneration by macroscopic, radiographic and histological methods. Repeated-measure ANOVAs and t-tests were used for statistical analyses. RESULTS: From aspirated bone marrow, multi-potent, heterogeneous BM-MSCs purified from hematopoietic stem cell contamination were obtained. FGF-2 significantly enhanced pig BM-MSC osteogenic differentiation and proliferation, with 5 ng/ml determined as the optimal dosage. Pig BM-MSCs integrated readily with Gelfoam and maintained viability and proliferative ability. After integration with Gelfoam scaffolds, 2.4-5.8×10(7 autologous BM-MSCs (undifferentiated or differentiated were transplanted to each experimental DO site. Among 8 evaluable DO sites included in the final analyses, the experimental DO sites demonstrated less interfragmentary mobility, more advanced gap obliteration, higher mineral content and faster mineral apposition than the control sites, and all transplanted scaffolds

  18. AKT-modified autologous intracoronary mesenchymal stem cells prevent remodeling and repair in swine infarcted myocardium

    Institute of Scientific and Technical Information of China (English)

    YU Yun-sheng; SHEN Zhen-ya; YE Wen-xue; HUANG Hao-yue; HUA Fei; CHEN Yi-huan; CHEN Ke; LAO Wei-jie; TAO Li

    2010-01-01

    Background Transplantation of adult bone marrow-derived mesenchymal stem cells (MSCs) has been proposed as a strategy for cardiac repair following myocardial damage. However cell transplantation strategies to replace lost myocardium are limited by the inability to deliver large numbers of cells that resist peritransplantation graft cell death. Accordingly, we set out to isolate and expand adult swine bone marrow-derived MSCs, and to engineer these cells to overexpress AKT1 (protein kinase B), to test the hypothesis that AKT1 -engineered MSCs are more resistant to apoptosis and can enhance cardiac repair after transplantation into the ischemic swine heart.Methods The CDS (regulation domain of AKT1) AKT1-cDNA fragment was amplified, and MSCs were transfected following synthesis with a pCDH1-AKT1 shuttling plasmid. Western blotting analysis and real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed. Myocardial infarction (Ml) models were constructed in Meishan pigs, and cardiac function was evaluated by magnetic resonance imaging (MRI) measurements and echocardiography 4 weeks later. All pigs were assigned to four groups: control (A), DMEM (B), MSC (C), and AKT-transfected (D). MSCs were transfected with the AKT1 gene, and autologous BrdU-labeled stem cells (1 × 107/5 ml) were injected into left anterior descending coronary atery (LAD) of the infarct heart in groups C and D. In group B, DMEM was injected using the same approach. In group A, there was no injection following LAD occlusion. After 4 weeks, cardiac function and regional perfusion measurements were repeated by MRI and echocardiography, and histological characteristics of the hearts were assessed. Connecxin-43 (CX-43), BrdU, and von Willebrand factor (VWF) immunoreactivity was tested using enzyme linked immunosorbent assay (ELISA). Vascular endothelial growth factor (VEGF), transforming growth factor-(31 (TGF-p1) were analyzed at the same time.Results AKT1-cDNA was cloned into p

  19. Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model

    Science.gov (United States)

    Tanaka, Yuya; Shirasawa, Bungo; Takeuchi, Yuriko; Kawamura, Daichi; Nakamura, Tamami; Samura, Makoto; Nishimoto, Arata; Ueno, Koji; Morikage, Noriyasu; Hosoyama, Tohru; Hamano, Kimikazu

    2016-01-01

    Mesenchymal stem cells (MSCs) constitute one of the most powerful tools for therapeutic angiogenesis in infarcted hearts. However, conventional MSC transplantation approaches result in insufficient therapeutic effects due to poor retention of graft cells in severe ischemic diseases. Cell sheet technology has been developed as a new method to prolong graft cell retention even in ischemic tissue. Recently, we demonstrated that hypoxic pretreatment enhances the therapeutic efficacy of cell sheet implantation in infarcted mouse hearts. In this study, we investigated whether hypoxic pretreatment activates the therapeutic functions of bone marrow-derived MSC (BM-MSC) sheets and improves cardiac function in rabbit infarcted hearts following autologous transplantation. Production of vascular endothelial growth factor (VEGF) was increased in BM-MSC monolayer sheets and it peaked at 48 h under hypoxic culture conditions (2% O2). To examine in vivo effects, preconditioned autologous BM-MSC sheets were implanted into a rabbit old myocardial infarction model. Implantation of preconditioned BM-MSC sheets accelerated angiogenesis in the peri-infarcted area and decreased the infarcted area, leading to improvement of the left ventricular function of the infarcted heart. Importantly, the therapeutic efficacy of the preconditioned BM-MSC sheets was higher than that of standardly cultured sheets. Thus, implantation of autologous preconditioned BM-MSC sheets is a feasible approach for enhancing therapeutic angiogenesis in chronically infarcted hearts. PMID:27347329

  20. Science Letters: Brain natriuretic peptide: A potential indicator of cardiomyogenesis after autologous mesenchymal stem cell transplantation?

    Institute of Scientific and Technical Information of China (English)

    LI Nan; WANG Jian-an

    2006-01-01

    We observed in a pilot study that there was a transient elevation of brain natriuretic peptide (BNP) level shortly after the transplantation in the patient with ischemic heart failure, which is unexplainable by the simultaneous increase of the cardiac output and six-minute walk distance. Similar findings were observed in the phase I trial. We postulated on the basis of the finding of Fukuda in vitro that this transient elevation of BNP level against the improvement of cardiac function and exercise capacity might indicate cardiomyogenesis in patients after mesenchymal stem cell transplantation. Further study is warranted to verify the hypothesis.

  1. Role of the autologous mesenchymal stem cells compared with platelet rich plasma on cicatrization of cutaneous wounds in diabetic mice

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    Napoleão M. Argolo Neto

    Full Text Available Abstract: Chronic cutaneous lesions affect 15% of diabetic human patients and represent a risk 15 to 46 times larger of limb amputations compared to people with normal glycemia. It is assumed that half of these amputations could be prevented by early treatment of wounds, for example, with proper cell therapy. Objectives: In this study, the action of the autologous transplant of mesenchymal stem-cells (MSC was evaluated compared to the treatment with autologous platelet rich plasma (PRP in the cicatrization of cutaneous lesions induced in diabetic mice. These animals were previously treated with streptozootocin to induce diabetes mellitus and round wounds of 1.5cm in diameter were created in the posterior region. Diameters of the wounds and healing time were evaluated during 30 days and the results were submitted to variance analysis and Tukey's test average. It was noticed that the animals treated with MSC presented a more accelerated cicatrization of the cutaneous lesion than the animals treated with PRP. However, the treatment with PRP presented better results than just the daily asepsis of the lesions with saline or covering them with semi-permeable bandage. Besides, the use of semi-permeable bandage kept the cutaneous lesions of diabetic mice did not interfere negatively with cicatrization, proved to be harmless to use, but kept the cutaneous lesions more hydrated than the ones exposed to the environment.

  2. Use of autologous mesenchymal stem cells derived from bone marrow for the treatment of naturally injured spinal cord in dogs.

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    Penha, Euler Moraes; Meira, Cássio Santana; Guimarães, Elisalva Teixeira; Mendonça, Marcus Vinícius Pinheiro; Gravely, Faye Alice; Pinheiro, Cláudia Maria Bahia; Pinheiro, Taiana Maria Bahia; Barrouin-Melo, Stella Maria; Ribeiro-Dos-Santos, Ricardo; Soares, Milena Botelho Pereira

    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 days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury.

  3. Use of Autologous Mesenchymal Stem Cells Derived from Bone Marrow for the Treatment of Naturally Injured Spinal Cord in Dogs

    Science.gov (United States)

    Penha, Euler Moraes; Meira, Cássio Santana; Guimarães, Elisalva Teixeira; Mendonça, Marcus Vinícius Pinheiro; Gravely, Faye Alice; Pinheiro, Cláudia Maria Bahia; Pinheiro, Taiana Maria Bahia; Barrouin-Melo, Stella Maria; Ribeiro-dos-Santos, Ricardo; Soares, Milena Botelho Pereira

    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 days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury. PMID:24723956

  4. Use of Autologous Mesenchymal Stem Cells Derived from Bone Marrow for the Treatment of Naturally Injured Spinal Cord in Dogs

    Directory of Open Access Journals (Sweden)

    Euler Moraes Penha

    2014-01-01

    Full Text Available 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 days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury.

  5. Feasibility of Treating Irradiated Bone with Intramedullary Delivered Autologous Mesenchymal Stem Cells

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    Bérengère Phulpin

    2011-01-01

    Full Text Available Background. We aimed to explore (i the short-term retention of intramedullary implanted mesenchymal stem cells BMSCs and (ii their impact on the bone blood flow and metabolism in a rat model of hindlimb irradiation. Methods. Three months after 30 Gy irradiation, fourteen animals were referred into 2 groups: a sham-operated group (n=6 and a treated group (n=8 in which 111In-labelled BMSCs (2×106 cells were injected in irradiated tibias. Bone blood flow and metabolism were assessed by serial T99mc-HDP scintigraphy and 1-wk cell retention by recordings of T99mc/111In activities. Results. The amount of intramedullary implanted BMSCs was of 70% at 2 H, 40% at 48 H, and 38% at 168 H. Bone blood flow and bone metabolism were significantly increased during the first week after cell transplantation, but these effects were found to reduce at 2-mo followup. Conclusion. Short-term cell retention produced concomitant enhancement in irradiated bone blood flow and metabolism.

  6. Preparation of a nano- and micro-fibrous decellularized scaffold seeded with autologous mesenchymal stem cells for inguinal hernia repair

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    Zhang Y

    2017-02-01

    Full Text Available Yinlong Zhang,1,* Yuanyuan Zhou,1,* Xu Zhou,2,* Bin Zhao,1,* Jie Chai,1 Hongyi Liu,1 Yifei Zheng,1 Jinling Wang,3 Yaozong Wang,4 Yilin Zhao2 1Medical College, Xiamen University, 2Department of Oncology and Vascular Intervention Radiology, 3Department of Emergency, 4Department of Orthopaedics, Zhongshan Hospital, Xiamen University, Xiamen, People’s Republic of China *These authors contributed equally to this work Abstract: Prosthetic meshes used for hernioplasty are usually complicated with chronic pain due to avascular fibrotic scar or mesh shrinkage. In this study, we developed a tissue-engineered mesh (TEM by seeding autologous bone marrow-derived mesenchymal stem cells onto nanosized fibers decellularized aorta (DA. DA was achieved by decellularizing the aorta sample sequentially with physical, mechanical, biological enzymatic digestion, and chemical detergent processes. The tertiary structure of DA was constituted with micro-, submicro-, and nanosized fibers, and the original strength of fresh aorta was retained. Inguinal hernia rabbit models were treated with TEMs or acellular meshes (AMs. After implantation, TEM-treated rabbit models showed no hernia recurrence, whereas AM-treated animals displayed bulges in inguinal area. At harvest, TEMs were thicker, have less adhesion, and have stronger mechanical strength compared to AMs (P<0.05. Moreover, TEM showed better cell infiltration, tissue regeneration, and neovascularization (P<0.05. Therefore, these cell-seeded DAs with nanosized fibers have potential for use in inguinal hernioplasty. Keywords: nanobiomaterial, tissue engineering, inguinal hernia, hernioplasty, decellularized aorta 

  7. Preparation of a nano- and micro-fibrous decellularized scaffold seeded with autologous mesenchymal stem cells for inguinal hernia repair

    Science.gov (United States)

    Zhang, Yinlong; Zhou, Yuanyuan; Zhou, Xu; Zhao, Bin; Chai, Jie; Liu, Hongyi; Zheng, Yifei; Wang, Jinling; Wang, Yaozong; Zhao, Yilin

    2017-01-01

    Prosthetic meshes used for hernioplasty are usually complicated with chronic pain due to avascular fibrotic scar or mesh shrinkage. In this study, we developed a tissue-engineered mesh (TEM) by seeding autologous bone marrow-derived mesenchymal stem cells onto nanosized fibers decellularized aorta (DA). DA was achieved by decellularizing the aorta sample sequentially with physical, mechanical, biological enzymatic digestion, and chemical detergent processes. The tertiary structure of DA was constituted with micro-, submicro-, and nanosized fibers, and the original strength of fresh aorta was retained. Inguinal hernia rabbit models were treated with TEMs or acellular meshes (AMs). After implantation, TEM-treated rabbit models showed no hernia recurrence, whereas AM-treated animals displayed bulges in inguinal area. At harvest, TEMs were thicker, have less adhesion, and have stronger mechanical strength compared to AMs (P<0.05). Moreover, TEM showed better cell infiltration, tissue regeneration, and neovascularization (P<0.05). Therefore, these cell-seeded DAs with nanosized fibers have potential for use in inguinal hernioplasty. PMID:28260890

  8. Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.

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    Sara Llufriu

    Full Text Available Uncontrolled studies of mesenchymal stem cells (MSCs in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL on magnetic resonance imaging (MRI at 6 months and at the end of the study.Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS 3.0-6.5 were randomized to receive IV 1-2×10(6 bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite, and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects.At baseline 9 patients were randomized to receive MSCs (n = 5 or placebo (n = 4. One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1-8.8 vs 12.3, 95% CI = 4.4-34.5, p = 0.064, and at the end of study to reduced mean GEL (-2.8±5.9 vs 3±5.4, p = 0.075. No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+ cells in blood of MSCs treated patients.Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266.

  9. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells

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    Ra Jeong Chan

    2011-10-01

    Full Text Available Abstract Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that ex-vivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here.

  10. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture

    Science.gov (United States)

    Muir, Peter; Hans, Eric C.; Racette, Molly; Volstad, Nicola; Sample, Susannah J.; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L.; Bloom, Debra D.; Bleedorn, Jason A.; Hao, Zhengling; Amene, Ermias; Suresh, M.; Hematti, Peiman

    2016-01-01

    Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response

  11. Randomized Comparison of Allogeneic Vs. Autologous Mesenchymal Stem Cells for Non-lschemic Dilated Cardiomyopathy: POSEIDON-DCM Trial

    Science.gov (United States)

    Hare, Joshua M.; DiFede, Darcy L; Castellanos, Angela M; Florea, Victoria; Landin, Ana M; El-Khorazaty, Jill; Khan, Aisha; Mushtaq, Muzammil; Lowery, Maureen H; Byrnes, John J; Hendel, Robert C; Cohen, Mauricio G; Alfonso, Carlos E; Valasaki, Krystalenia; Pujol, Marietsy V; Golpanian, Samuel; Ghersin, Eduard; Fishman, Joel E; Pattany, Pradip; Gomes, Samirah A; Delgado, Cindy; Miki, Roberto; Abuzeid, Fouad; Vidro-Casiano, Mayra; Premer, Courtney; Medina, Audrey; Porras, Valeria; Hatzistergos, Konstantinos E.; Anderson, Erica; Mendizabal, Adam; Mitrani, Raul; Heldman, Alan W.

    2016-01-01

    Background While human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic non-ischemic dilated cardiomyopathy (NIDCM). Objectives The POSEIDON-DCM trial is a randomized comparison of safety and efficacy of autologous (auto) vs. allogeneic (allo) bone marrow-derived hMSCs in NIDCM. Methods Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients (age: 55.8 ± 11.2; 32% female) received hMSCs (100 million) by transendocardial stem cell injection (TESI) in ten left ventricular sites by NOGA Catheter. Treated patients were evaluated at baseline, 30 days, 3-, 6-, and 12-months for safety: serious adverse events (SAE), and efficacy endpoints: Ejection Fraction (EF), Minnesota Living with Heart Failure Questionnaire (MLHFQ), Six Minute Walk Test (6MWT), MACE, and immune-biomarkers. This trial is registered with ClinicalTrials.gov, #NCT01392625. Results There were no 30-day treatment-emergent (TE)-SAEs. 12-month SAE incidence was 28.2% (95% CI: 12.8, 55.1) in allo, and 63.5% (95% CI: 40.8, 85.7; p=0.1004) in auto. One allo-group patient developed an elevated donor specific cPRA. EF increased in allo by 8.0 units (95% Cl: 2.8, 13.2; p=0.004), and in auto: 5.4 units (95% Cl: −1.4, 12.1; p=0.116, allo vs. auto p=0.4887). 6MWT increased for allo: 37.0 meters (95% Cl: 2.0 to 72.0; p=0.04), but not auto: 7.3 meters (95% Cl: −47.8, 33.3; p=0.71, auto vs. allo p=0.0168). MLHFQ score decreased in allo (p=0.0022), and auto (p=0.463; p=0.172). The MACE rate was lower in allo vs. auto (p=0.0186). Tumor necrosis factor alpha (TNF-α) decreased (p=0.0001 for each), to a greater extent in allo vs. auto at six-months (p=0.05). Conclusion These findings demonstrate safety and support greater, clinically meaningful efficacy of allo-hMSC vs. auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are

  12. Neural stem cell-like cells derived from autologous bone mesenchymal stem cells for the treatment of patients with cerebral palsy

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    Chen Guojun

    2013-01-01

    Full Text Available Abstract Background Stem cell therapy is a promising treatment for cerebral palsy, which refers to a category of brain diseases that are associated with chronic motor disability in children. Autologous MSCs may be a better cell source and have been studied for the treatment of cerebral palsy because of their functions in tissue repair and the regulation of immunological processes. Methods To assess neural stem cell–like (NSC-like cells derived from autologous marrow mesenchymal stem cells as a novel treatment for patients with moderate-to-severe cerebral palsy, a total of 60 cerebral palsy patients were enrolled in this open-label, non-randomised, observer-blinded controlled clinical study with a 6-months follow-up. For the transplantation group, a total of 30 cerebral palsy patients received an autologous NSC-like cells transplantation (1-2 × 107 cells into the subarachnoid cavity and rehabilitation treatments whereas 30 patients in the control group only received rehabilitation treatment. Results We recorded the gross motor function measurement scores, language quotients, and adverse events up to 6 months post-treatment. The gross motor function measurement scores in the transplantation group were significantly higher at month 3 (the score increase was 42.6, 95% CI: 9.8–75.3, P=.011 and month 6 (the score increase was 58.6, 95% CI: 25.8–91.4, P=.001 post-treatment compared with the baseline scores. The increase in the Gross Motor Function Measurement scores in the control group was not significant. The increases in the language quotients at months 1, 3, and 6 post-treatment were not statistically significant when compared with the baseline quotients in both groups. All the 60 patients survived, and none of the patients experienced serious adverse events or complications. Conclusion Our results indicated that NSC-like cells are safe and effective for the treatment of motor deficits related to cerebral palsy. Further randomised clinical

  13. The Fate and Distribution of Autologous Bone Marrow Mesenchymal Stem Cells with Intra-Arterial Infusion in Osteonecrosis of the Femoral Head in Dogs

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    Hongting Jin

    2016-01-01

    Full Text Available This study aimed to investigate if autologous bone marrow mesenchymal stem cells (MSCs could treat osteonecrosis of the femoral head (ONFH and what the fate and distribution of the cells are in dogs. Twelve Beagle dogs were randomly divided into two groups: MSCs group and SHAM operated group. After three weeks, dogs in MSCs group and SHAM operated group were intra-arterially injected with autologous MSCs and 0.9% normal saline, respectively. Eight weeks after treatment, the necrotic volume of the femoral heads was significantly reduced in MSCs group. Moreover, the trabecular bone volume was increased and the empty lacunae rate was decreased in MSCs group. In addition, the BrdU-positive MSCs were unevenly distributed in femoral heads and various vital organs. But no obvious abnormalities were observed. Furthermore, most of BrdU-positive MSCs in necrotic region expressed osteocalcin in MSCs group and a few expressed peroxisome proliferator-activated receptor-γ (PPAR-γ. Taken together, these data indicated that intra-arterially infused MSCs could migrate into the necrotic field of femoral heads and differentiate into osteoblasts, thus improving the necrosis of femoral heads. It suggests that intra-arterial infusion of autologous MSCs might be a feasible and relatively safe method for the treatment of femoral head necrosis.

  14. Effects of Tongxinluo-facilitated cellular cardiomyoplasty with autologous bone marrow-mesenchymal stem cells on postinfarct swine hearts

    Institute of Scientific and Technical Information of China (English)

    QIAN Hai-yan; LU Min-jie; ZHAO Shi-hua; YANG Yue-jin; HUANG Ji; GAO Run-lin; DOU Ke-fei; YANG Guo-sheng; LI Jian-jun; SHEN Rui; HE Zuo-xiang

    2007-01-01

    Background Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion.Methods Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n=7); group 2,administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n=7); group 3,MSCs alone (n=7) and group 4, TXL + MSCs (n=7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3×107 cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint.Results At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P<0.0001); the capillary density was also significantly greater than in the control group,group 2 or 3 both in the infarcted zone (P<0.0001) and the peri-infarct zone (P<0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the

  15. Guided bone regeneration in pig calvarial bone defects using autologous mesenchymal stem/progenitor cells - a comparison of different tissue sources.

    Science.gov (United States)

    Stockmann, Philipp; Park, Jung; von Wilmowsky, Cornelius; Nkenke, Emeka; Felszeghy, Endre; Dehner, Jan-Friedrich; Schmitt, Christian; Tudor, Christian; Schlegel, Karl Andreas

    2012-06-01

    Due to donor side morbidity and the absence of osteogenic properties in bone substitutes, there is a growing need for an alternative to traditional bone grafting within the scope of tissue engineering. This animal study was conducted to compare the in vivo osteogenic potential of adipose-derived (AD), periosteum-derived (PD) and bone marrow-derived (BM) mesenchymal stem/progenitor cells (MSC). Autologous mesenchymal stem/progenitor cells of named tissue origin were induced into osteogenic differentiation following in vitro cell expansion. Ex vivo cultivated cells were seeded on a collagen scaffold and subsequently added to freshly created monocortical calvarial bone defects in 21 domestic pigs. Pure collagen scaffold served as a control defect. The animals were sacrificed at specific time points and de novo bone formation was quantitatively analyzed by histomorphometry. Bone volume/total defect volume (BV/TV) and the mineralization rate of newly formed bone were compared among the groups. In the early stages of wound healing, up to 30 days, the test defects did not show better bone regeneration than those in the control defect, but the bone healing process in the test defects was accelerated in the later stage compared to those in the control defect. All the test defects showed complete osseous healing after 90 days compared to those in the control defect. During the observation period, no significant differences in BV/TV and mineralization of newly formed bone among the test defects were observed. Irrespective of the tissue sources of MSC, the speed and pattern of osseous healing after cell transplantations into monocortical bone defects were comparable. Our results indicate that the efficiency of autologous AD-MSC, PD-MSC and BM-MSC transplantation following ex vivo cell expansion is not significantly different for the guided regeneration of bone defects.

  16. Autologous mesenchymal stem cells applied on the pressure ulcers had produced a surprising outcome in a severe case of neuromyelitis optica

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    Adriana Octaviana Dulamea

    2015-01-01

    Full Text Available Recent studies provided evidence that mesenchymal stem cells (MSCs have regenerative potential in cutaneous repair and profound immunomodulatory properties making them a candidate for therapy of neuroimmunologic diseases. Neuromyelitis optica (NMO is an autoimmune, demyelinating central nervous system disorder characterized by a longitudinally extensive spinal cord lesion. A 46-year-old male diagnosed with NMO had relapses with paraplegia despite treatment and developed two stage IV pressure ulcers (PUs on his legs. The patient consented for local application of autologous MSCs on PUs. MSCs isolated from the patient′s bone marrow aspirate were multiplied in vitro during three passages and embedded in a tridimensional collagen-rich matrix which was applied on the PUs. Eight days after MSCs application the patient showed a progressive healing of PUs and improvement of disability. Two months later the patient was able to walk 20 m with bilateral assistance and one year later he started to walk without assistance. For 76 months the patient had no relapse and no adverse event was reported. The original method of local application of autologous BM-MSCs contributed to healing of PUs. For 6 years the patient was free of relapses and showed an improvement of disability. The association of cutaneous repair, sustained remission of NMO and improvement of disability might be explained by a promotion/optimization of recovery mechanisms in the central nervous system even if alternative hypothesis should be considered. Further studies are needed to assess the safety and efficacy of mesenchymal stem cells in NMO treatment.

  17. The effect of leukocyte-reduced platelet-rich plasma on the proliferation of autologous adipose-tissue derived mesenchymal stem cells.

    Science.gov (United States)

    Loibl, Markus; Lang, Siegmund; Brockhoff, Gero; Gueorguiev, Boyko; Hilber, Franz; Worlicek, Michael; Baumann, Florian; Grechenig, Stephan; Zellner, Johannes; Huber, Michaela; Valderrabano, Victor; Angele, Peter; Nerlich, Michael; Prantl, Lukas; Gehmert, Sebastian

    2016-01-01

    Clinical application of platelet-rich plasma (PRP) and stem cells has become more and more important in regenerative medicine during the last decade. However, differences in PRP preparations may contribute to variable PRP compositions with unpredictable effects on a cellular level. In the present study, we modified the centrifugation settings in order to provide a leukocyte-reduced PRP and evaluated the interactions between PRP and adipose-tissue derived mesenchymal stem cells (ASCs).PRP was obtained after modification of three different centrifugation settings and investigated by hemogram analysis, quantification of protein content and growth factor concentration. ASCs were cultured in serum-free α-MEM supplemented with autologous 10% or 20% leukocyte-reduced PRP. Cell cycle kinetics of ASCs were analyzed using flow cytometric analyses after 48 hours.Thrombocytes in PRP were concentrated, whereas erythrocytes, and white blood cells (WBC) were reduced, independent of centrifugation settings. Disabling the brake further reduced the number of WBCs. A higher percentage of cells in the S-phase in the presence of 20% PRP in comparison to 10% PRP and 20% fetal calf serum (FCS) advocates the proliferation stimulation of ASCs.These findings clearly demonstrate considerable differences between three PRP separation settings and assist in safeguarding the combination of leukocyte-reduced PRP and stem cells for regenerative therapies.

  18. Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

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    Boos AM

    2014-11-01

    Full Text Available Anja M Boos,1,* Annika Weigand,1,* Gloria Deschler,1 Thomas Gerber,2 Andreas Arkudas,1 Ulrich Kneser,1 Raymund E Horch,1 Justus P Beier11Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg FAU, Erlangen, 2Institute of Physics, University of Rostock, Rostock, Germany *These authors contributed equally to this work Abstract: New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2, and different carrier materials (fibrin, cell culture medium, autologous serum was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 µg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin. Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly

  19. Isolation of mesenchymal stem cells from equine umbilical cord blood

    OpenAIRE

    Thomsen Preben D; Heerkens Tammy; Koch Thomas G; Betts Dean H

    2007-01-01

    Background: There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC) have been isolated from fresh umbilical cord blood of humans collected non-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is lo...

  20. Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: Viable therapy for type III.C. a diabetes mellitus

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    Umang G Thakkar

    2014-12-01

    Full Text Available Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC along with his bone marrow derived hematopoietic stem cells (BM-HSC. Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus.

  1. Human fetal mesenchymal stem cells.

    Science.gov (United States)

    O'Donoghue, Keelin; Chan, Jerry

    2006-09-01

    Stem cells have been isolated at all stages of development from the early developing embryo to the post-reproductive adult organism. However, the fetal environment is unique as it is the only time in ontogeny that there is migration of stem cells in large numbers into different organ compartments. While fetal neural and haemopoietic stem cells (HSC) have been well characterised, only recently have mesenchymal stem cells from the human fetus been isolated and evaluated. Our group have characterised in human fetal blood, liver and bone marrow a population of non-haemopoietic, non-endothelial cells with an immunophenotype similar to adult bone marrow-derived mesenchymal stem cells (MSC). These cells, human fetal mesenchymal stem cells (hfMSC), are true multipotent stem cells with greater self-renewal and differentiation capacity than their adult counterparts. They circulate in first trimester fetal blood and have been found to traffic into the maternal circulation, engrafting in bone marrow, where they remain microchimeric for decades after pregnancy. Though fetal microchimerism has been implicated in the pathogenesis of autoimmune disease, the biological role of hfMSC microchimerism is unknown. Potential downstream applications of hfMSC include their use as a target cell for non-invasive pre-natal diagnosis from maternal blood, and for fetal cellular and gene therapy. Using hfMSC in fetal therapy offers the theoretical advantages of avoidance of immune rejection, increased engraftment, and treatment before disease pathology sets in. Aside from allogeneic hfMSC in utero transplantation, the use of autologous hfMSC has been brought a step forward with the development of early blood sampling techniques, efficient viral transduction and clonal expansion. Work is ongoing to determine hfMSC fate post-transplantation in murine models of genetic disease. In this review we will examine what is known about hfMSC biology, as well as discussing areas for future research. The

  2. [Effects of local transplantation of autologous adipose-derived mesenchymal stem cells on the formation of hyperplastic scar on rabbit ears].

    Science.gov (United States)

    Chen, L; Wang, D L; Wei, Z R; Wang, B; Qi, J P; Sun, G F

    2016-10-20

    Objective: To investigate the effects of local transplantation of autologous adipose-derived mesenchymal stem cells (ADSCs) on the formation of hyperplastic scar on rabbit ears. Methods: ADSCs were isolated from inguinal fat of six New Zealand rabbits and then sub-cultured. ADSCs of the third passage of each rabbit were used in the following experiments. Six full-thickness skin defect wounds with diameter of 6 mm on the ventral surface of every rabbit ear were made. Wound healing and local-tissue proliferation were observed, and complete epithelization time of wounds and formation time of hyperplastic scar were recorded. The wounds on left ears were selected as group ADSCs, and the wounds on right ears were selected as control group, with 36 wounds in each group. After the complete epithelization of wounds (post injury day 25), 0.2 mL bromodeoxyuridine (BrdU) labeled autologous ADSCs with the concentration of 5×10(6) per milliliter were injected into each wound of the rabbit of group ADSCs, while the same amount of phosphate buffer solution was injected into each wound of the rabbit of control group. The frequency of injection was once every 5 days, totally for 3 times, and the latter 2 times were injected into scars generated from healed wound. Hyperplastic scars of rabbits of two groups were harvested on the fifth day after the third injection, then the morphology was observed by HE staining, and the arrangement of collagen in hyperplastic scar was observed by VG staining. The distribution of BrdU-labeled ADSCs in the hyperplastic scar was observed with fluorescence microscope. The protein content of type Ⅰ collagen, type Ⅲ collagen, transforming growth factor β1 (TGF-β1), and decorin in hyperplastic scar were detected by enzyme-linked immunosorbent assay, and the mRNA expression of decorin and TGF-β1 in hyperplastic scar were tested by real-time fluorescent quantitative reverse transcription-polymerase chain reaction. Data were processed with paired t

  3. Isolation of mesenchymal stem cells from equine umbilical cord blood

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Heerkens, Tammy; Thomsen, Preben Dybdahl

    2007-01-01

    Background: There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC) have been isolated from fresh umbilical cord blood of humans collected non......-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low......, for the first time, the isolation of mesenchymal-like stem cells from fresh equine cord blood and their differentiation into osteocytes, chondrocytes and adipocytes. This novel isolation of equine cord blood MSCs and their preliminary in vitro differentiation positions the horse as the ideal pre-clinical animal...

  4. Repair of Segmental Load-Bearing Bone Defect by Autologous Mesenchymal Stem Cells and Plasma-Derived Fibrin Impregnated Ceramic Block Results in Early Recovery of Limb Function

    Directory of Open Access Journals (Sweden)

    Min Hwei Ng

    2014-01-01

    Full Text Available Calcium phosphate-based bone substitutes have not been used to repair load-bearing bone defects due to their weak mechanical property. In this study, we reevaluated the functional outcomes of combining ceramic block with osteogenic-induced mesenchymal stem cells and platelet-rich plasma (TEB to repair critical-sized segmental tibial defect. Comparisons were made with fresh marrow-impregnated ceramic block (MIC and partially demineralized allogeneic bone block (ALLO. Six New Zealand White female rabbits were used in each study group and three rabbits with no implants were used as negative controls. By Day 90, 4/6 rabbits in TEB group and 2/6 in ALLO and MIC groups resumed normal gait pattern. Union was achieved significantly faster in TEB group with a radiological score of 4.50 ± 0.78 versus ALLO (1.06 ± 0.32, MIC (1.28 ± 0.24, and negative controls (0. Histologically, TEB group scored the highest percentage of new bone (82% ± 5.1% compared to ALLO (5% ± 2.5% and MIC (26% ± 5.2%. Biomechanically, TEB-treated tibiae achieved the highest compressive strength (43.50 ± 12.72 MPa compared to those treated with ALLO (15.15 ± 3.57 MPa and MIC (23.28 ± 6.14 MPa. In conclusion, TEB can repair critical-sized segmental load-bearing bone defects and restore limb function.

  5. 自体骨髓间充质神经干细胞移植治疗帕金森病的疗效观察%Transplanting autologous mesenchymal stem cells in the treatment of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    刘定华; 顾鲁军; 韩伯军; 王庆广; 洪珊珊; 高恒; 万美荣; 叶英

    2016-01-01

    Objective To explore the curative effect and safety of transplanting autologous mesenchymal stem cells to patients with Parkinson's disease.Methods Forty-two patients with Parkinson's disease were selected and randomly divided into a control group and a research group,each of 21.Both groups were given routine treatment and rehabilitation,but the research group was additionally provided with autologous bone marrow mesenchymal stem cell transplantation.Bone marrow mesenchymal stem cells were isolated from the patients,cultured and transplanted back into the patients totally 4 times at intervals of 5 to 10 days.Before the treatment and 4 weeks and 3 months later,the clinical functioning of both groups was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS).Four weeks and 3 months after the treatment,the peripheral blood expression of vascular endothelial growth factor (VEGF),the expression of interleukin 10 (IL-10) and the expression of CSF tumor necrosis factor alpha (TNF-α) in cerebrospinal fluid were compared between the 2 groups.Results The average UPDRS score of the research group decreased from (41.26± 17.92) at four weeks to (33.67± 17.77) at 3 months after the treatment,both significantly lower than before the treatment,and significantly lower than the scores of the control group at the same time points [(47.13±18.35) and (39.03±16.50)].During the treatment,no severe adverse reactions were observed among the research group.Moreover,after the treatment the blood expression of VEGF and the expression of IL-10 in cerebrospinal fluid were significantly improved in the research group,while that of TNF-α was significantly reduced compared to before the treatment.nclusions The transplantation of autologous mesenchymal stem cells can safely promote nerve function in Parkinson's disease patients.It is worth applying in clinical practice.%目的 探讨自体骨髓间充质神经干细胞移植治疗帕金森病的疗效及安全性.方法

  6. Cryptococcal meningitis post autologous stem cell transplantation.

    Science.gov (United States)

    Chaaban, S; Wheat, L J; Assi, M

    2014-06-01

    Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with non-Hodgkin's lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/μL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2 O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSFCryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving.

  7. In Vivo Study of Ligament-Bone Healing after Anterior Cruciate Ligament Reconstruction Using Autologous Tendons with Mesenchymal Stem Cells Affinity Peptide Conjugated Electrospun Nanofibrous Scaffold

    Directory of Open Access Journals (Sweden)

    Jingxian Zhu

    2013-01-01

    Full Text Available Electrospinning nanofibrous scaffold was commonly used in tissue regeneration recently. Nanofibers with specific topological characteristics were reported to be able to induce osteogenic differentiation of MSCs. In this in vivo study, autologous tendon grafts with lattice-like nanofibrous scaffold wrapping at two ends of autologous tendon were used to promote early stage of ligament-bone healing after rabbit ACL reconstruction. To utilize native MSCs from bone marrow, an MSCs specific affinity peptide E7 was conjugated to nanofibrous meshes. After 3 months, H-E assessment and specific staining of collagen type I, II, and III showed direct ligament-bone insertion with typical four zones (bone, calcified fibrocartilage, fibrocartilage, and ligament in bioactive scaffold reconstruction group. Diameters of bone tunnel were smaller in nanofibrous scaffold conjugated E7 peptide group than those in control group. The failure load of substitution complex also indicated a stronger ligament-bone insertion healing using bioactive scaffold. In conclusion, lattice-like nanofibrous scaffold with specific MSCs affinity peptide has great potential in promoting early stage of ligament-bone healing after ACL reconstruction.

  8. Allogeneic and autologous mode of stem cell transplantation in regenerative medicine: which way to go?

    Science.gov (United States)

    Mamidi, Murali Krishna; Dutta, Susmita; Bhonde, Ramesh; Das, Anjan Kumar; Pal, Rajarshi

    2014-12-01

    Stem cell transplantation is a generic term covering different techniques. However there is argument over the pros and cons of autologous and allogeneic transplants of mesenchymal stem cells (MSCs) for regenerative therapy. Given that the MSCs have already been proven to be safe in patients, we hypothesize that allogeneic transplantation could be more effective and cost-effective as compared to autologous transplantation specifically in older subjects who are the likely victims of degenerative diseases. This analysis is based on the scientific logic that allogeneic stem cells extracted in large numbers from young and healthy donors could be physiologically, metabolically and genetically more stable. Therefore stem cells from young donors may be expected to exhibit higher vigor in secreting trophic factors leading to activation of host tissue-specific stem cells and also be more efficient in remodeling the micro-environmental niche of damaged tissue.

  9. Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Nagwa El-Badri

    2013-01-01

    Full Text Available Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy is a promising alternative for islet transplantation in type 2 diabetic patients who fail to control hyperglycemia even with insulin injection. Autologous stem cell transplantation may provide the best outcome for those patients, since autologous cells are readily available and do not entail prolonged hospital stays or sustained immunotoxic therapy. Among autologous adult stem cells, mesenchymal stem cells (MSCs therapy has been applied with varying degrees of success in both animal models and in clinical trials. This review will focus on the advantages of MSCs over other types of stem cells and the possible mechanisms by which MSCs transplant restores normoglycemia in type 2 diabetic patients. Sources of MSCs including autologous cells from diabetic patients and the use of various differentiation protocols in relation to best transplant outcome will be discussed.

  10. 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...

  11. Autologous Stem Cell Transplant for AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Vivek Roy

    2012-01-01

    Full Text Available AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors has increased treatment options. Autologous stem cell transplant (ASCT has been used in the treatment of AL amyloidosis for many years. It is associated with high rates of hematologic response and improvement in organ function. However, transplant carries considerable risks. Careful patient selection is important to minimize transplant related morbidity and mortality and ensure optimal patient outcomes. As newer more affective therapies become available the role and timing of ASCT in the overall treatment strategy of AL amyloidosis will need to be continually reassessed.

  12. Mesenchymal Stem Cells from Wharton's Jelly and Amniotic Fluid.

    Science.gov (United States)

    Joerger-Messerli, Marianne S; Marx, Caterina; Oppliger, Byron; Mueller, Martin; Surbek, Daniel V; Schoeberlein, Andreina

    2016-02-01

    The discovery of mesenchymal stem cells (MSCs) in perinatal sources, such as the amniotic fluid (AF) and the umbilical connective tissue, the so-called Wharton's jelly (WJ), has transformed them into promising stem cell grafts for the application in regenerative medicine. The advantages of AF-MSCs and WJ-MSCs over adult MSCs, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), include their minimally invasive isolation procedure, their more primitive cell character without being tumourigenic, their low immunogenicity and their potential autologous application in congenital disorders and when cryopreserved in adulthood. This chapter gives an overview of the biology of AF-MSCs and WJ-MSCs, and their regenerative potential based on the results of recent preclinical and clinical studies. In the end, open questions concerning the use of WJ-MSCs and AF-MSCs in regenerative medicine will be emphasized.

  13. 自体脂肪源性间充质干细胞修复兔软骨缺损的实验研究%Repair of articular cartilage defects by autologous adipose derived mesenchymal stem cell experiment with rabbits

    Institute of Scientific and Technical Information of China (English)

    杨雨润; 田华

    2008-01-01

    Objective To evaluate the effectiveness of autologous adipose derived mesenchymal stem cells (ADSCs) tranduced by adenovirus-mediated human transforming growth factor 2 (Ad-hTGF-β2) gene in the repair of articular cartilage defects. Methods Rabbit ADSCs were obtained, cultured, and transfected with Ad-hTGF-β2 containing human transforming growth factor (hTGF) - β2. Three days later RT-PCR was used to detect the mRNA expression of hTGF- β2 in the ADSCs, and ELISA was used to detect the protein expression of hTGF-β2 in the supernatant, phosphorylation of Smad was examined by Western blotting. Articular cartilage defects at the femoral trochlea were made on 20 rabbits (40 sides) so as to establish animal models. The culture-expanded rabbit ADSCs transfected with Ad-hTGF- 2 were seeded on poly (L-lactic-co-glycolic acid) (PLGA) scaffolds. The cell-adhered PLGA scaffolds were implanted into the articular cartilage defects. Plain PLGA was implanted into the left-side defects of 10 rabbits as control group and the defects of 10 sides remained untreated as blank control group. The rabbits were sacrificed 4, 12, and 24 weeks after the operation respectively. The specimens of defects were examined histologically and stained immunohistochemically for type Ⅱ collagen. Results After transfection the ADSCs expressed mRNA and protein expression of hTGF- β2 and Western blotting showed bands of phosphorylated Smad. The cartilage specimens harvested from the experimental group rabbits demonstrated hyaline cartilage formation mingled closely with the nearby tissues and expression of type Ⅱ collagen. However, only fibroblasts, not cartilage-like cells, were seen in the control groups that lacked the expression of type Ⅱ collagen too. Conclusion Culture-expanded autologous ADSCs adhered with PLGA composites facilitate the formation of hyaline-cartilage.%目的 评价腺病毒介导的人转化生长因子β2(Ad-hTGF-β2)基因转染自体兔脂肪间充质干细胞(ADSCs)

  14. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2015-01-01

    Full Text Available The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better

  15. Mesenchymal Stem Cells and Tooth Engineering

    Institute of Scientific and Technical Information of China (English)

    Li Peng; Ling Ye; Xue-dong Zhou

    2009-01-01

    Tooth loss compromises human oral health. Although several prosthetic methods, such as artificial denture and dental implants, are clinical therapies to tooth loss problems, they are thought to have safety and usage time issues. Recently, tooth tissue engineering has attracted more and more attention. Stem cell based tissue engineering is thought to be a promising way to replace the missing tooth. Mesenchymal stem cells (MSCs) are multipotent stem cells which can differentiate into a variety of cell types. The potential MSCs for tooth regeneration mainly include stem cells from human exfoliated deciduous teeth (SHEDs), adult dental pulp stem cells (DPSCs), stem cells from the apical part of the papilla (SCAPs), stem cells from the dental follicle (DFSCs), periodontal ligament stem cells (PDLSCs) and bone marrow derived mesenchymal stem cells (BMSCs). This review outlines the recent progress in the mesenchymal stem cells used in tooth regeneration.

  16. Effect of activated autologous platelet-rich plasma on chondrogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells in vitro%自体激活富血小板血浆干预兔骨髓间充质干细胞体外成软骨分化的研究**★

    Institute of Scientific and Technical Information of China (English)

    王善正; 王宸; 芮云峰

    2013-01-01

      背景:自体富血小板血浆激活后可释放多种生长因子,可以促进骨髓间充质干细胞的增殖与分化。目的:观察自体激活富血小板血浆对体外培养的兔骨髓间充质干细胞向成软骨细胞分化的影响。方法:取兔股骨骨髓,全骨髓贴壁法分离培养骨髓间充质干细胞;取第3代骨髓间充质干细胞,分别应用体积分数10%自体激活富血小板血浆和体积分数10%胎牛血清培养液进行体外培养,观察其向成软骨细胞分化情况。结果与结论:分离培养的兔骨髓间充质干细胞呈长梭形,传代后细胞生长迅速。流式细胞仪检测发现第3代细胞高表达CD29、CD44,而低表达CD45。免疫荧光细胞化学染色显示经自体激活富血小板血浆诱导的骨髓间充质干细胞表达Ⅱ型胶原;实时荧光定量PCR 检测发现经自体激活富血小板血浆诱导的骨髓间充质干细胞Ⅱ型胶原α1链基因和聚集蛋白聚糖基因表达明显高于经胎牛血清诱导的骨髓间充质干细胞(P <0.01)。可见自体激活富血小板血浆具有促进兔骨髓间充质干细胞向软骨细胞方向分化的潜能。%BACKGROUND:Platelet-rich plasma, when activated, could secret multiple growth factors which may promote the proliferation and differentiation of bone marrow-derived mesenchymal stem cel s. OBJECTIVE:To explore the effect of activated autologous platelet-rich plasma on the chondrogenic differentiation of rabbit bone marrow-derived mesenchymal stem cel s in vitro. METHODS:Rabbit bone marrow-derived mesenchymal stem cel s were isolated using the whole bone marrow adherence method. Passage 3 bone marrow-derived mesenchymal stem cel s were in vitro cultured with 10%activated autologous platelet-rich plasma and 10%fetal bovine serum separately. Chondrogenic differentiation of rabbit bone marrow-derived mesenchymal stem cel s in vitro was observed. RESULTS AND CONCLUSION:Bone marrow

  17. 自体骨髓间充质干细胞经动脉介入移植治疗犬糖尿病%Intra-arterial transplantation of autologous bone marrow mesenchymal stem cells for treatment of diabetes in dogs

    Institute of Scientific and Technical Information of China (English)

    王立梅; 崔晓兰; 丁明超; 窦立冬; 李倩倩; 王意忠

    2012-01-01

    背景:目前多数研究倾向于将骨髓间充质干细胞经静脉移植等方法移植入糖尿病动物模型体内,而缺少将骨髓间充质干细胞经动脉介入移植入糖尿病动物模型胰腺内的相关研究.目的:用自体骨髓间充质干细胞经动脉介入移植入糖尿病犬胰腺内,观察骨髓间充质干细胞的分布、分化、对糖尿病的治疗效果及安全性.方法:将30只家犬随机分为骨髓间充质干细胞组(治疗组,n=13),糖尿病模型对照组(模型组,n=10)和对照组(n=7).治疗组及模型组通过静脉注射四氧嘧啶建立糖尿病模型.造模后,治疗组进行胰岛素治疗,同时进行自体骨髓间充质干细胞的动脉介入移植.模型组仅接受胰岛素治疗,对照组则不接受任何治疗.结果与结论:与模型组比较,治疗组于移植后第12周的胰岛素用量明显减少(P < 0.05),血清C-肽水平明显升高(P < 0.05).治疗组于移植后第4周及12周的组织病理切片显示,心脏、肝脏、脾脏、肺脏、肾脏的组织结构清晰,均未发生坏死、纤维化,与模型组及对照组比较,移植后各器官组织形态无明显异常改变.移植后第4周,骨髓间充质干细胞主要分布在胰腺及肾脏内,免疫荧光发现胰腺内存在CM-DiI和胰岛素共表达细胞.表明将骨髓间充质干细胞经动脉介入移植入糖尿病犬胰腺内来治疗糖尿病的方法,是安全有效的.%BACKGROUND: At present, most researchers focus on intravenous transplantation of bone marrow mesenchymal stem cells (BMSCs) into diabetic animal models. There are few studies that describe transplantation of BMSCs into the pancreas of diabetic animal models via arterial intervention.OBJECTIVE: To investigate the distribution and differentiation of autologous BMSCs transplanted into the pancreas of a dog model of diabetes via the arterial intervention as well as the therapeutic effects and safety.METHODS: 30 dogs were randomly divided into BMSCs group

  18. Mesenchymal stem cells derived from adipose tissue are not affected by renal disease.

    Science.gov (United States)

    Roemeling-van Rhijn, Marieke; Reinders, Marlies E J; de Klein, Annelies; Douben, Hannie; Korevaar, Sander S; Mensah, Fane K F; Dor, Frank J M F; IJzermans, Jan N M; Betjes, Michiel G H; Baan, Carla C; Weimar, Willem; Hoogduijn, Martin J

    2012-10-01

    Mesenchymal stem cells are a potential therapeutic agent in renal disease and kidney transplantation. Autologous cell use in kidney transplantation is preferred to avoid anti-HLA reactivity; however, the influence of renal disease on mesenchymal stem cells is unknown. To investigate the feasibility of autologous cell therapy in patients with renal disease, we isolated these cells from subcutaneous adipose tissue of healthy controls and patients with renal disease and compared them phenotypically and functionally. The mesenchymal stem cells from both groups showed similar morphology and differentiation capacity, and were both over 90% positive for CD73, CD105, and CD166, and negative for CD31 and CD45. They demonstrated comparable population doubling times, rates of apoptosis, and were both capable of inhibiting allo-antigen- and anti-CD3/CD28-activated peripheral blood mononuclear cell proliferation. In response to immune activation they both increased the expression of pro-inflammatory and anti-inflammatory factors. These mesenchymal stem cells were genetically stable after extensive expansion and, importantly, were not affected by uremic serum. Thus, mesenchymal stem cells of patients with renal disease have similar characteristics and functionality as those from healthy controls. Hence, our results indicate the feasibility of their use in autologous cell therapy in patients with renal disease.

  19. Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy.

    Science.gov (United States)

    Ding, Dah-Ching; Chang, Yu-Hsun; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2015-01-01

    The human umbilical cord is a promising source of mesenchymal stem cells (HUCMSCs). Unlike bone marrow stem cells, HUCMSCs have a painless collection procedure and faster self-renewal properties. Different derivation protocols may provide different amounts and populations of stem cells. Stem cell populations have also been reported in other compartments of the umbilical cord, such as the cord lining, perivascular tissue, and Wharton's jelly. HUCMSCs are noncontroversial sources compared to embryonic stem cells. They can differentiate into the three germ layers that promote tissue repair and modulate immune responses and anticancer properties. Thus, they are attractive autologous or allogenic agents for the treatment of malignant and nonmalignant solid and soft cancers. HUCMCs also can be the feeder layer for embryonic stem cells or other pluripotent stem cells. Regarding their therapeutic value, storage banking system and protocols should be established immediately. This review critically evaluates their therapeutic value, challenges, and future directions for their clinical applications.

  20. Mesenchymal stem cells (MSCs) as skeletal therapeutics-an update

    DEFF Research Database (Denmark)

    Saeed, H.; Ahsan, M.; Saleem, Z.

    2016-01-01

    Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repair....../regeneration. In this context, both, autologous and allogeneic cell transfer options have been utilized. Studies suggest that MSCs are transplanted either alone by mixing with autogenous plasma/serum or by loading onto repair/induction supportive resorb-able scaffolds. Thus, this review is aimed at highlighting a wide range...

  1. Role of Mesenchymal Stem Cells In Tumorigenesis

    Science.gov (United States)

    2009-08-01

    stem cells ( BMDC ), which then acts in a paracrine fashion on the cancer cells to enhance their invasion [7]. Interestingly the group of Karnoub showed...AD_________________ AWARD NUMBER: W81XWH-08-1-0523 TITLE: Role of Mesenchymal Stem Cells in...DATES COVERED 1 Aug 2008 – 31 Jul 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Role of Mesenchymal Stem Cells in Tumorigenesis 5b. GRANT

  2. Mesenchymal Stem Cells Reduce Murine Atherosclerosis Development

    NARCIS (Netherlands)

    Frodermann, Vanessa; van Duijn, Janine; van Pel, Melissa; van Santbrink, Peter J.; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C. A.

    2015-01-01

    Mesenchymal stem cells (MSCs) have regenerative properties, but recently they were also found to have immunomodulatory capacities. We therefore investigated whether MSCs could reduce atherosclerosis, which is determined by dyslipidaemia and chronic inflammation. We adoptively transferred MSCs into l

  3. Therapeutic Potential of Autologous Stem Cell Transplantation for Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Chaitanya Purandare

    2012-01-01

    Full Text Available Background. Cerebral palsy (CP is a severe disabling disease with worldwide incidence being 2 to 3 per 1000 live births. CP was considered as a noncurable, nonreparative disorder, but stem cell therapy offers a potential treatment for CP. Objective. The present study evaluates the safety and efficacy of autologous bone-marrow-derived mononuclear cell (BMMNCs transplantation in CP patient. Material and Methods. In the present study, five infusions of autologous stem cells were injected intrathecally. Changes in neurological deficits and improvements in function were assessed using Gross Motor Function Classification System (GMFCS-E&R scale. Results. Significant motor, sensory, cognitive, and speech improvements were observed. Bowel and bladder control has been achieved. On the GMFCS-E&R level, the patient was promoted from grade III to I. Conclusion. In this study, we report that intrathecal infusion of autologous BMMNCs seems to be feasible, effective, and safe with encouraging functional outcome improvements in CP patient.

  4. Mesenchymal stem cells in regenerative rehabilitation.

    Science.gov (United States)

    Nurkovic, Jasmin; Dolicanin, Zana; Mustafic, Fahrudin; Mujanovic, Rifat; Memic, Mensur; Grbovic, Vesna; Skevin, Aleksandra Jurisic; Nurkovic, Selmina

    2016-06-01

    [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient's medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this review is to discuss possibilities, limitations, and future clinical applications of mesenchymal stem cells. [Subjects and Methods] The authors have identified and discussed clinically and scientifically relevant articles from PubMed that have met the inclusion criteria. [Results] Direct treatment of muscle injuries, stroke, damaged peripheral nerves, and cartilage with mesenchymal stem cells has been demonstrated to be effective, with synergies seen between cellular and physical therapies. Over the past few years, several researchers, including us, have shown that there are certain limitations in the use of mesenchymal stem cells. Aging and spontaneous malignant transformation of mesenchymal stem cells significantly affect the functionality of these cells. [Conclusion] Definitive conclusions cannot be made by these studies because limited numbers of patients were included. Studies clarifying these results are expected in the near future.

  5. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  6. Mesenchymal stem cells in oral reconstructive surgery

    DEFF Research Database (Denmark)

    Jakobsen, C; Sørensen, J A; Kassem, M

    2013-01-01

    This study evaluated clinical outcomes following intraoperative use of adult mesenchymal stem cells (MSCs) in various oral reconstructive procedures. PubMed was searched without language restrictions from 2000 to 2011 using the search words stem cell, oral surgery, tissue engineering, sinus lift...

  7. Mesenchymal stem cells as a therapeutic tool in tissue and organ regeneration

    Directory of Open Access Journals (Sweden)

    Anna Bajek

    2011-01-01

    Full Text Available Tissue engineering is an interdisciplinary field that offers new opportunities for regeneration of diseased and damaged tissue with the use of many different cell types,including adult stem cells. In tissue engineering and regenerative medicine the most popular are mesenchymal stem cells (MSCs isolated from bone marrow. Bone marrow mesenchymal stem cells are a potential source of progenitor cells for osteoblasts, chondroblasts, adipocytes, skeletal muscles and cardiomyocytes. It has also been shown that these cells can differentiate into ecto- and endodermal cells, e.g. neuronal cells, glial cells, keratinocytes and hepatocytes. The availability of autologous MSCs, their proliferative potential and multilineage differentiation capacity make them an excellent tool for tissue engineering and regenerative medicine. The aim of this publication is to present characteristic and biological properties of mesenchymal stem cells isolated from bone marrow.

  8. Isolation of mesenchymal stem cells from equine umbilical cord blood

    Directory of Open Access Journals (Sweden)

    Thomsen Preben D

    2007-05-01

    Full Text Available Abstract Background There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC have been isolated from fresh umbilical cord blood of humans collected non-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low. The hypothesis of this study was that equine MSCs could be isolated from fresh whole equine cord blood. Results Cord blood was collected from 7 foals immediately after foaling. The mononuclear cell fraction was isolated by Ficoll density centrifugation and cultured in a DMEM low glucose based media at 38.5°C in humidified atmosphere containing 5% CO2. In 4 out of 7 samples colonies with MSC morphology were observed. Cellular morphology varied between monolayers of elongated spindle-shaped cells to layered cell clusters of cuboidal cells with shorter cytoplasmic extensions. Positive Alizarin Red and von Kossa staining as well as significant calcium deposition and alkaline phosphatase activity confirmed osteogenesis. Histology and positive Safranin O staining of matrix glycosaminoglycans illustrated chondrogenesis. Oil Red O staining of lipid droplets confirmed adipogenesis. Conclusion We here report, for the first time, the isolation of mesenchymal-like stem cells from fresh equine cord blood and their differentiation into osteocytes, chondrocytes and adipocytes. This novel isolation of equine cord blood MSCs and their preliminary in vitro differentiation positions the horse as the ideal pre-clinical animal model for proof-of-principle studies of cord blood derived MSCs.

  9. Immunological characteristics of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Cíntia de Vasconcellos Machado

    2013-01-01

    Full Text Available Although bone marrow is the main source, mesenchymal stem cells have already been isolated from various other tissues, such as the liver, pancreas, adipose tissue, peripheral blood and dental pulp. These plastic adherent cells are morphologically similar to fibroblasts and have a high proliferative potential. This special group of cells possesses two essential characteristics: self-renewal and differentiation, with appropriate stimuli, into various cell types. Mesenchymal stem cells are considered immunologically privileged, since they do not express costimulatory molecules, required for complete T cell activation, on their surface. Several studies have shown that these cells exert an immunosuppressive effect on cells from both innate and acquired immunity systems. Mesenchymal stem cells can regulate the immune response in vitro by inhibiting the maturation of dendritic cells, as well as by suppressing the proliferation and function of T and B lymphocytes and natural killer cells. These special properties of mesenchymal stem cells make them a promising strategy in the treatment of immune mediated disorders, such as graft-versus-host disease and autoimmune diseases, as well as in regenerative medicine. The understanding of immune regulation mechanisms of mesenchymal stem cells, and also those involved in the differentiation of these cells in various lineages is primordial for their successful and safe application in different areas of medicine.

  10. Autologous stem cells in neurology: is there a future?

    Science.gov (United States)

    de Munter, Johannes P J M; Wolters, Erik C

    2013-01-01

    Stem cells seem very promising in the treatment of degenerative neurological diseases for which there are currently no or limited therapeutic strategies. However, their clinical application meets many regulatory hurdles. This article gives an overview of stem cells, their potential healing capacities as well as their identified and potential risks, such as tumor formation, unwanted immune responses and the transmission of adventitious agents. As there is no clinical experience with embryonic and induced pluripotent stem cells (as the result of their unacceptable risk on tumor formation), most attention will be paid to fresh autologous adult stem cells (ASCs). To evaluate eventual clinical benefits, preclinical studies are essential, though their value is limited as in these studies, various types of stem cells, with different histories of procurement and culturing, are applied in various concentrations by various routes of administration. On top of that, in most animal studies allogenic human, thus non-autologous, stem cells are applied, which might mask the real effects. More reliable, though small-sized, clinical trials with autologous ASCs did show satisfying clinical benefits in regenerative medicine, without major health concerns. One should wonder, though, why it is so hard to get compelling evidence for the healing and renewing capacities of these stem cells when these cells indeed are really essential for tissue repair during life. Why so many hurdles have to be taken before health authorities such as the European Medicine Agency (EMA) and/or the Food and Drug Administration (FDA) approve stem cells in the treatment of (especially no-option) patients.

  11. Early Clinical Results of Implantation of Tantalum Rod Combined Transplantation of Autologous Bone Marrow Mesenchy-mal Stem Cells for Early Stage of Avascular Necrosis of Femoral Head%钽棒植入联合自体骨髓间充质干细胞移植治疗早期股骨头缺血性坏死

    Institute of Scientific and Technical Information of China (English)

    梁红锁; 黄克; 李林; 张波; 韦程寿

    2014-01-01

    Objective:To study the effects of implantation of tantalum rod and transplantation of autologous bone mar-row mesenchymal stem cells for early stage of avascular necrosis of femoral head .Methods:27 patients with avascular necrosis of femoral head in the early stage were treated with implantation of tantalum rod and transplantation of autolo-gous bone marrow mesenchymal stem cells .Results:The average period of follow-up was thirteen months (7 ~ 24 months) .Pain of all patients disappeared .The movement range of the hip joint was normal or approximate to normal . Except two cases evolved to stage of ARCOⅢ ,X-ray showed that cystic degeneration disappeared .The Harris score was 54 .2 ± 7 .1 before operation and it increased significantly to 83 .9 ± 8 .6 after operation .Conclusion:It has the ad-vantage to minimal damage of implantation of tantalum rod and transplantation of autologous bone marrow mesenchy-mal stem cells for early stage of avascular necrosis of femoral head .It is an effective way for the treatment of femoral head necrosis .The short-term efficacy is good .%目的:观察钽棒植入联合自体骨髓间充质干细胞移植治疗早期股骨头缺血性坏死的临床疗效。方法:对27例ARCOⅠ、Ⅱ期的ANFH患者采用股骨头髓芯减压后植入钽棒并联合自体骨髓间充质干细胞移植。结果:所有患者经过7~24个月(平均13个月)的随访,关节疼痛基本消失,活动范围接近或恢复正常,除2例患者进展为ARCOⅢ期外,其余股骨头均无塌陷,影像学检查结果示股骨头囊性变消失,Harris评分由术前的(54.2±7.1)分提高到术后(83.9±8.6)分。结论:钽棒植入联合自体骨髓间充质干细胞移植治疗早期股骨头缺血性坏死,具有创伤小、疗效确切等优点,近期临床疗效良好。

  12. cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo

    NARCIS (Netherlands)

    Siddappa, Ramakrishnaiah; Martens, Anton; Doorn, Joyce; Leusink, Anouk; Olivo, Cristina; Licht, Ruud; van Rijn, Linda; Gaspar, Claudia; Fodde, Riccardo; Janssen, Frank; van Blitterswijk, Clemens; de Boer, Jan

    2008-01-01

    Tissue engineering of large bone defects is approached through implantation of autologous osteogenic cells, generally referred to as multipotent stromal cells or mesenchymal stem cells (MSCs). Animal-derived MSCs successfully bridge large bone defects, but models for ectopic bone formation as well a

  13. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects

    Institute of Scientific and Technical Information of China (English)

    Yang Wang; Zheng-wei Li; Min Luo; Ya-jun Li; Ke-qiang Zhang

    2015-01-01

    The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some re-spects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit+bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit+bone marrow mesenchymal stem cells+extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit+bone marrow mesenchymal stem cells+extracellular matrix gel group, followed by the polylactic glycolic acid conduit+bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the poly-lactic glycolic acid conduit+bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve ifbers, and a completely degraded and resorbed conduit, in the polylac-tic glycolic acid conduit+bone marrow mesenchymal stem cells+extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit+bone marrow mesenchymal stem cells+extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is ben-eifcial for the regeneration and functional reconstruction of sciatic nerve. Better regeneration was found with the

  14. Mesenchymal stem cells targeting the GVHD

    Institute of Scientific and Technical Information of China (English)

    WANG Liang; ZHAO Robert ChunHua

    2009-01-01

    Acute graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. About 35% -5% of hematopoietic stem cell transplant (HSCT) recipients will develop acute GVHD. It is associated with considerable morbidity and mortality, particularly in patients who do not respond to primary therapy, which usually consists of glucocorticoids(steroids). Most of the available second-line and third-line treatments for sterold-refractory acute GVHD induce severe immunodeficiency, which is commonly accompanied by lethal infectious complications. Mesenchymal stem cells (MSCs) have been shown to mediate immunomodulatory effects. The recently elucidated immunosuppreseive potential of mesenchymal stem cells has set the stage for their clinical testing as cellular immunosuppressants, MSCs have been used in patients with steroid-refractory acute GVHD, and encouraging responses have been obtained in many studies. The utility of MSCs for the treatment of GVHD is becoming clear.

  15. Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds

    DEFF Research Database (Denmark)

    Mygind, Tina; Stiehler, Maik; Baatrup, Anette

    2007-01-01

    Culture of osteogenic cells on a porous scaffold could offer a new solution to bone grafting using autologous human mesenchymal stem cells (hMSC) from the patient. We compared coralline hydroxyapatite scaffolds with pore sizes of 200 and 500 microm for expansion and differentiation of hMSCs. We...... polymerase chain reaction for 10 osteogenic markers. The 500-microm scaffolds had increased proliferation rates and accommodated a higher number of cells (shown by DNA content, scanning electron microscopy and fluorescence microscopy). Thus the porosity of a 3D microporous biomaterial may be used to steer h......MSC in a particular direction. We found that dynamic spinner flask cultivation of hMSC/scaffold constructs resulted in increased proliferation, differentiation and distribution of cells in scaffolds. Therefore, spinner flask cultivation is an easy-to-use inexpensive system for cultivating hMSCs on small...

  16. Clinical Neurofunctional Rehabilitation of a Cat with Spinal Cord Injury after Hemilaminectomy and Autologous Stem Cell Transplantation

    Science.gov (United States)

    Penha, Euler M.; Aguiar, Paulo H. P.; Barrouin-Melo, Stella Maria; de Lima, Ricardo S.; da Silveira, Ana Carolina C.; Otelo, Ana Rosa S.; Pinheiro, Claudia Maria B.; Ribeiro-dos-Santos, Ricardo; Soares, Milena B. P.

    2012-01-01

    Stem cell-based therapy has been investigated in a number of degenerative and traumatic diseases, including spinal cord injury. In the present study, we investigated the use of autologous mesenchymal stem cells in the functional rehabilitation of a domestic cat presenting a compressive L1-L5 fracture. Bone marrow cells collected by puncture of the iliac crest were cultured to obtain mesenchymal stem cells three weeks before surgery. Hemilaminectomy was performed, followed by injection of the mesenchymal stem cells in the injured area. Clinical evaluation of the animal prior to surgery showed absence of pain, muscular tonus, and panniculi reflexes. Seven days after surgery and cell transplantation the examination revealed a progressive recovery of the panniculus reflexes and of the responses to superficial and deep pain stimuli despite the low proprioceptive and hyperreflexic ataxic hind limbs. Physiotherapy protocols were applied for clinical rehabilitation after surgery. The cat’s first steps, three-minute weight-bearing, and intestine and urinary bladder partial reestablishment were observed 75 days post-surgery. Our results indicate the therapeutic potential of mesenchymal stem cells in chronic spinal cord injuries. PMID:24298368

  17. Transplantation of Reprogrammed Autologous Stem Cells for Chronic Pain and Drug Abuse

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-11-1-0673 TITLE: Transplantation of Reprogrammed Autologous Stem Cells for Chronic Pain and Drug Abuse PRINCIPAL...CONTRACT NUMBER Transplantation of Reprogrammed Autologous Stem Cells for Chronic Pain and Drug Abuse 5b. GRANT NUMBER: W81XWH-11-1-0673 5c. PROGRAM...Tolerance, Drug abuse , Cell cultures, Spinal transplantation of autologous stem cells, Animal behavioral tests 16. SECURITY CLASSIFICATION OF: 17

  18. Inactivated Mesenchymal Stem Cells Maintain Immunomodulatory Capacity

    NARCIS (Netherlands)

    Luk, Franka; de Witte, Samantha F. H.; Korevaar, Sander S.; Roemeling, Marieke; Franquesa, Marcella; Strini, Tanja; van den Engel, Sandra; Gargesha, Madhusudhana; Roy, Debashish; Dor, Frank J. M. F.; Horwitz, Edwin M.; de Bruin, Ron W. F.; Betjes, Michiel G. H.; Baan, Carla C.; Hoogduijn, Martin J.

    2016-01-01

    Mesenchymal stem cells (MSC) are studied as a cell therapeutic agent for treatment of various immune diseases. However, therapy with living culture-expanded cells comes with safety concerns. Furthermore, development of effective MSC immunotherapy is hampered by lack of knowledge of the mechanisms of

  19. Current Perspectives in Mesenchymal Stem Cell Therapies for Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Baldur Kristjánsson

    2014-01-01

    Full Text Available Osteoarthritis (OA is a degenerative joint disease most commonly occurring in the ageing population. It is a slow progressive condition resulting in the destruction of hyaline cartilage followed by pain and reduced activity. Conventional treatments have little effects on the progression of the condition often leaving surgery as the last option. In the last 10 years tissue engineering utilising mesenchymal stem cells has been emerging as an alternative method for treating OA. Mesenchymal stem cells (MSCs are multipotent progenitor cells found in various tissues, most commonly bone marrow and adipose tissue. MSCs are capable of differentiating into osteocytes, adipocytes, and chondrocytes. Autologous MSCs can be easily harvested and applied in treatment, but allogenic cells can also be employed. The early uses of MSCs focused on the implantations of cell rich matrixes during open surgeries, resulting in the formation of hyaline-like durable cartilage. More recently, the focus has completely shifted towards direct intra-articular injections where a great number of cells are suspended and injected into affected joints. In this review the history and early uses of MSCs in cartilage regeneration are reviewed and different approaches in current trends are explained and evaluated.

  20. 自体骨髓间充质干细胞移植治疗颅脑损伤后痉挛性瘫痪%S pastic paralysis after traumatic brain injury treated by autologous bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    伊西才; 魏礼洲; 黑悦; 龙乾发; 王博晨; 田沁涛; 周跃飞; 刘卫平

    2016-01-01

    目的:探讨应用自体骨髓间充质干细胞治疗颅脑损伤后痉挛性瘫痪的临床疗效。方法回顾性分析第四军医大学西京医院神经外科自2009年5月至2014年4月治疗的33例颅脑损伤后痉挛性瘫痪患者,完成4次自体骨髓间充质干细胞移植,每周1次,每次经腰椎穿刺蛛网膜下腔注射,细胞数为2×107,移植前、移植后1个月、3个月、6个月通过改良Ashworth分级、Brunnstrom分级评估患侧上下肢肌张力、运动功能,并行脑PET/CT、脑电图、偏瘫肢体肌电图检查。结果移植后1个月开始Brunnstrom分级较移植前改善。移植后3个月开始Ashworth分级较移植前改善。5例移植后3个月头颅PET/CT见脑葡萄糖代谢减低较前改善。临床观察未发现明显不良反应,脑电图、偏瘫肢体肌电图检查未见明显变化。结论自体骨髓间充质干细胞移植对颅脑损伤后痉挛性瘫痪的肢体肌张力增高和运动障碍均有改善,移植后6个月内通过临床观察及影像学检查未发现不良反应,为临床治疗颅脑损伤后遗症提供了新方法。%Objective To investigate the clinical efficacy of autologous bone marrow mesenchymal stem cells transplantation on spastic paralysis after traumatic brain injury. Methods During May 2009 to April 2014, the clinical data about 33 patients with spastic paralysis after traumatic brain injury were retrospectively analyzed. Bone marrow puncture was performed under general anesthesia. Bone marrow mesenchymal stem cells (2 ×107) were intrathecally transplanted once a week for four weeks. The measurement points contain before treatment, one month, three months and six months after treatment. Muscular tension and movement disorders were evaluated using modified Ashworth scale and Brunnstrom stage classification respectively. Besides that, brain PET/CT, electroencephalo-graphy and electromyography were recorded. Results Muscular tone was improved one

  1. Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Raquel Taléns-Visconti; Ana Bonora; Ramiro Jover; Vicente Mirabet; Francisco Carbonell; José Vicente Castell; María José Gómez-Lechón

    2006-01-01

    AIM: To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells (ADSC) and bone marrow-derived mesenchymal stem cells (BMSC) in vitro. Transdifferentiation of BMSC into hepatic cells in vivo has been described. Adipose tissue represents an accessible source of ADSC, with similar characteristics to BMSC.METHODS: BMSCs were obtained from patients undergoing total hip arthroplasty and ADSC from human adipose tissue obtained from lipectomy. Cells were grown in medium containing 15% human serum. Cultures were serum deprived for 2 d before cultivating under similar pro-hepatogenic conditions to those of liver development using a 2-step protocol with sequential addition of growth factors, cytokines and hormones. Hepatic differentiation was RT-PCR-assessed and liver-marker genes were immunohistochemically analysed.RESULTS: BMSC and ADSC exhibited a fibroblastic morphology that changed to a polygonal shape when cells differentiated. Expression of stem cell marker Thy1 decreased in differentiated ADSC and BMSC. However, the expression of the hepatic markers, albumin and CYPs increased to a similar extent in differentiated BMSC and ADSC. Hepatic gene activation could be attributed to increased liver-enriched transcription factors (C/EBPβ and HNF4α), as demonstrated by adenoviral expression vectors.CONCLUSION: Mesenchymal stem cells can be induced to hepatogenic transdifferentiation in vitro. ADSCs have a similar hepatogenic differentiation potential to BMSC,but a longer culture period and higher proliferation capacity. Therefore, adipose tissue may be an ideal source of large amounts of autologous stem cells, and may become an alternative for hepatocyte regeneration, liver cell transplantation or preclinical drug testing.

  2. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

    Science.gov (United States)

    Cortez, Afonso José Pereira; Dulley, Frederico Luiz; Saboya, Rosaura; Mendrone Júnior, Alfredo; Amigo Filho, Ulisses; Coracin, Fabio Luiz; Buccheri, Valéria; Linardi, Camila da Cruz Gouveia; Ruiz, Milton Artur; Chamone, Dalton de Alencar Fischer

    2011-01-01

    Background Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. Objectives To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. Methods A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. Results The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. Conclusion Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not been previously reported

  3. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Afonso José Pereira Cortez

    2011-02-01

    Full Text Available BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not

  4. Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

    Directory of Open Access Journals (Sweden)

    Harpa Marius Mihai

    2015-12-01

    Full Text Available Background: We hypothesized that an ideal heart valve replacement would be acellular valve root scaffolds seeded with autologous stem cells. To test this hypothesis, we prepared porcine acellular pulmonary valves, seeded them with autologous adipose derived stem cells (ADSCs and implanted them in sheep and compared them to acellular valves.

  5. Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient.

    Science.gov (United States)

    Hayakawa, Kayoko; Takasaki, Tomohiko; Tsunemine, Hiroko; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Mawatari, Momoko; Fujiya, Yoshihiro; Yamamoto, Kei; Ohmagari, Norio; Kato, Yasuyuki

    2015-08-01

    The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein.

  6. Mesenchymal Stem Cells in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Olcay Ergurhan Kiroglu

    2015-03-01

    Full Text Available Neurodegenerative diseases are almost incurable, debilitating, and they might be fatal, because of limited neurogenesis in nervous system, presence of inhibitory substances and inhibition of recovery due to development of glial scar. Despite many treatment strategies of neurodegenerative diseases no full cure has been achieved. The successful results for mesenchymal stem cells applications on muscles, heart and liver diseases and the application of these cells to the damaged area in particular, hypoxia, inflammation and apoptosis promise hope of using them for neurodegenerative diseases. Mesenchymal stem cells applications constitute a vascular and neuronal phenotype in Parkinsons disease, Huntingtons disease, Amyotrophic lateral sclerosis and Alzheimers disease. Stem cells release bioactive agents that lead to suppression of local immune system, reduction of free radicals, increase in angiogenesis, inhibition of fibrosis, and apoptosis. In addition, tissue stem cells, increase neuronal healing, stimulate proliferation and differentiation. These findings show that stem cells might be a hope of a cure in the treatment of neurodegenerative diseases and intensive work on this issue should continue.

  7. The effect of erythropoietin on autologous stem cell-mediated bone regeneration.

    Science.gov (United States)

    Nair, Ashwin M; Tsai, Yi-Ting; Shah, Krishna M; Shen, Jinhui; Weng, Hong; Zhou, Jun; Sun, Xiankai; Saxena, Ramesh; Borrelli, Joseph; Tang, Liping

    2013-10-01

    Mesenchymal stem cells (MSCs) although used for bone tissue engineering are limited by the requirement of isolation and culture prior to transplantation. Our recent studies have shown that biomaterial implants can be engineered to facilitate the recruitment of MSCs. In this study, we explore the ability of these implants to direct the recruitment and the differentiation of MSCs in the setting of a bone defect. We initially determined that both stromal derived factor-1alpha (SDF-1α) and erythropoietin (Epo) prompted different degrees of MSC recruitment. Additionally, we found that Epo and bone morphogenetic protein-2 (BMP-2), but not SDF-1α, triggered the osteogenic differentiation of MSCs in vitro. We then investigated the possibility of directing autologous MSC-mediated bone regeneration using a murine calvaria model. Consistent with our in vitro observations, Epo-releasing scaffolds were found to be more potent in bridging the defect than BMP-2 loaded scaffolds, as determined by computed tomography (CT) scanning, fluorescent imaging and histological analyses. These results demonstrate the tremendous potential, directing the recruitment and differentiation of autologous MSCs has in the field of tissue regeneration.

  8. Application of autologous bone marrow mesenchymal stem cell-derived extracellular matrix scaffold on tissue engineering cartilage in vitro%自体骨髓间质干细胞外基质支架在体外软骨组织工程中的应用

    Institute of Scientific and Technical Information of China (English)

    唐成; 徐燕; 王黎明; 苗登顺; 裴璇; 魏波; 杜小涛; 金成哲

    2013-01-01

    Objective To evaluate the feasibility of the formation of tissue engineering cartilage in vitro by using autologous bone marrow mesenchymal stem cell-derived extracellular matrix (aBMSC-dECM)scaffold.Methods The autologous bone marrow mesenchymal stem cells were harvested from 5 New Zealand white rabbits which are two weeks old.The extracellular matrix was collected after 4 weeks culture and fabricated into aBMSC-dECM scaffold.The scaffold was investigated by a scanning electron microscope and HE staining.The autologous articular chondrocytes were isolated,cultured and seeded into the aBMSC-dECM scaffold.Live-Dead staining was analyzed 48 h after seeding.Gross morphological and volume measurement,HE staining,Safranin-O staining and type Ⅱ collagen immunohistochemistry staining,RT-PCRassay,and compression strength test were operated for the cell-scaffold composite at 1,2,4,and 6 weeks after the cultivation respectively.Atelocollagen scaffold was used as the control group.Results The aBMSC-dECM scaffold was three-dimensional and spongy.The engineered cartilage in aBMSC-dECM scaffold group appeared milk white in color with smooth and glossy surface.Compared with the atelocollagen scaffold group,the volume of engineered cartilage in aBMSC-dECM scaffold group significantly grew with time,the chondrocyte,proteoglycan and type Ⅱ collagen were gradually accumulated,the mRNA of type Ⅱ collage and Aggrecan were constantly expressed,and the compressive strength significantly increased with time.Conclusion The aBMSC-dECM scaffold could enhance the viability and biological function of chondrocytes,and promote engineered cartilage regeneration.It could be a novel candidate scaffold for cartilage tissue engineering.%目的 探讨利用自体骨髓间质干细胞外基质(autologous bone marrow mesenchymal stemcell-derived extracellular matrix,aBMSC-dECM)支架体外制备组织工程软骨的可行性.方法 取2周龄新西兰大白兔5只,分离、培养骨

  9. Human induced pluripotent stem cells on autologous feeders.

    Directory of Open Access Journals (Sweden)

    Kazutoshi Takahashi

    Full Text Available BACKGROUND: For therapeutic usage of induced Pluripotent Stem (iPS cells, to accomplish xeno-free culture is critical. Previous reports have shown that human embryonic stem (ES cells can be maintained in feeder-free condition. However, absence of feeder cells can be a hostile environment for pluripotent cells and often results in karyotype abnormalities. Instead of animal feeders, human fibroblasts can be used as feeder cells of human ES cells. However, one still has to be concerned about the existence of unidentified pathogens, such as viruses and prions in these non-autologous feeders. METHODOLOGY/PRINCIPAL FINDINGS: This report demonstrates that human induced Pluripotent Stem (iPS cells can be established and maintained on isogenic parental feeder cells. We tested four independent human skin fibroblasts for the potential to maintain self-renewal of iPS cells. All the fibroblasts tested, as well as their conditioned medium, were capable of maintaining the undifferentiated state and normal karyotypes of iPS cells. Furthermore, human iPS cells can be generated on isogenic parental fibroblasts as feeders. These iPS cells carried on proliferation over 19 passages with undifferentiated morphologies. They expressed undifferentiated pluripotent cell markers, and could differentiate into all three germ layers via embryoid body and teratoma formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that autologous fibroblasts can be not only a source for iPS cells but also be feeder layers. Our results provide a possibility to solve the dilemma by using isogenic fibroblasts as feeder layers of iPS cells. This is an important step toward the establishment of clinical grade iPS cells.

  10. Mesenchymal stem cells targeting the GVHD

    Institute of Scientific and Technical Information of China (English)

    ZHAO; Robert; ChunHua

    2009-01-01

    Acute graft-versus-host disease(GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues.About 35%-50% of hematopoietic stem cell transplant(HSCT) recipients will develop acute GVHD.It is associated with considerable morbidity and mortality,particularly in patients who do not respond to primary therapy,which usually consists of glucocorticoids(steroids).Most of the available second-line and third-line treatments for steroid-refractory acute GVHD induce severe immunodeficiency,which is commonly accompanied by lethal infectious complications.Mesenchymal stem cells(MSCs) have been shown to mediate immunomodulatory effects.The recently elucidated immunosuppressive potential of mesenchymal stem cells has set the stage for their clinical testing as cellular immunosuppressants,MSCs have been used in patients with steroid-refractory acute GVHD,and encouraging responses have been obtained in many studies.The utility of MSCs for the treatment of GVHD is becoming clear.

  11. Cartilage Engineering from Mesenchymal Stem Cells

    Science.gov (United States)

    Goepfert, C.; Slobodianski, A.; Schilling, A. F.; Adamietz, P.; Pörtner, R.

    Mesenchymal progenitor cells known as multipotent mesenchymal stromal cells or mesenchymal stem cells (MSC) have been isolated from various tissues. Since they are able to differentiate along the mesenchymal lineages of cartilage and bone, they are regarded as promising sources for the treatment of skeletal defects. Tissue regeneration in the adult organism and in vitro engineering of tissues is hypothesized to follow the principles of embryogenesis. The embryonic development of the skeleton has been studied extensively with respect to the regulatory mechanisms governing morphogenesis, differentiation, and tissue formation. Various concepts have been designed for engineering tissues in vitro based on these developmental principles, most of them involving regulatory molecules such as growth factors or cytokines known to be the key regulators in developmental processes. Growth factors most commonly used for in vitro cultivation of cartilage tissue belong to the fibroblast growth factor (FGF) family, the transforming growth factor-beta (TGF-β) super-family, and the insulin-like growth factor (IGF) family. In this chapter, in vivo actions of members of these growth factors described in the literature are compared with in vitro concepts of cartilage engineering making use of these growth factors.

  12. The secretome of mesenchymal stem cells: potential implications for neuroregeneration.

    Science.gov (United States)

    Paul, Gesine; Anisimov, Sergey V

    2013-12-01

    Mesenchymal stem cells have shown regenerative properties in many tissues. This feature had originally been ascribed to their multipotency and thus their ability to differentiate into tissue-specific cells. However, many researchers consider the secretome of mesenchymal stem cells the most important player in the observed reparative effects of these cells. In this review, we specifically focus on the potential neuroregenerative effect of mesenchymal stem cells, summarize several possible mechanisms of neuroregeneration and list key factors mediating this effect. We illustrate examples of mesenchymal stem cell treatment in central nervous system disorders including stroke, neurodegenerative disorders (such as Parkinson's disease, Huntington's disease, multiple system atrophy and cerebellar ataxia) and inflammatory disease (such as multiple sclerosis). We specifically highlight studies where mesenchymal stem cells have entered clinical trials.

  13. Autologous transplantation of bone marrow mesenchymal stem cells to improve ocular surface in severely damaged cases%自体骨髓间充质干细胞移植改善重度眼表损伤临床观察

    Institute of Scientific and Technical Information of China (English)

    陈洁; 潘志强; 骆非; 接英; 彭秀军

    2011-01-01

    Objective To evaluate the effect of autologous bone marrow mesenchymal stem cells (BMSC) in treating severely damaged ocular surface.Methods Four cases of corneal chemical burn and two cases of Stenven-Johnson Syndrome were enrolled in this study.The BMSCs were obtained and cultured in vitro.The cells were harvested afler 14 days and confirmed to be BMSCs.Then the cells were placed on an amniotic membrane (AM) and expanded until 90% confluence formation before using.After the abnormal conjunctival and corneal tissues were removed from the cornea,the AM coated autologous BMSCs were transplanted onto the corneal surface.Aftersurgery,antibiotics,steroid and lubricant eye drops were used and patients were examined by slit-lamp and impression cytology.Results In all the six treated eyes,the entire corneal epithelium was intact one week after surgery.The visual acuity improved in three eyes,two eyes kept at the same level and decreased in one eye.The ocular surface was smooth,but the new blood vessels didn't show significant reduction.After twelve weeks,the epithelial cells phenotype and goblet cells appeared on corneal surface.Conclusions Autologous BMSCs can improve ocular surface condition in severely damaged patients,which show potential use for treating limbal deficiency.%目的 评价自体骨髓间充质干细胞在严重眼表损伤移植后的治疗效果.方法 选取了化学烧伤4例,Stevens-Johnson综合征2例.骨髓间充质干细胞取自患者,细胞培养14 d后,经细胞检测鉴定为骨髓间充质干细胞,将细胞种植在羊膜表面,细胞扩增融合达90%后使用.手术切除表面结膜化组织达角膜缘外3 mm,将羊膜上培养的自体骨髓间充质干细胞移植到角膜及角膜缘表面,术后予抗生素、激素、人工泪液点眼治疗;病人定期随访,进行裂隙灯显微镜及印迹细胞学检查.结果 6例患眼均覆盖了含有自体骨髓间充质干细胞的羊膜片,术后1周角膜上皮完整.3

  14. Standard operating procedure for the good manufacturing practice-compliant production of human bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Roseti, Livia; Serra, Marta; Bassi, Alessandra

    2015-01-01

    According to the European Regulation (EC 1394/2007), Mesenchymal Stem Cells expanded in culture for clinical use are considered as Advanced Therapy Medicinal Products. As a consequence, they must be produced in compliance with Good Manufacturing Practice in order to ensure safety, reproducibility, and efficacy. Here, we report a Standard Operating Procedure describing the Good Manufacturing Practice-compliant production of Bone Marrow-derived Mesenchymal Stem Cells suitable for autologous implantation in humans. This procedure can be considered as a template for the development of investigational medicinal Mesenchymal Stem Cells-based product protocols to be enclosed in the dossier required for a clinical trial approval. Possible clinical applications concern local uses in the regeneration of bone tissue in nonunion fractures or in orthopedic and maxillofacial diseases characterized by a bone loss.

  15. Mesenchymal Stem Cells as a Potent Cell Source for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Elham Zomorodian

    2012-01-01

    Full Text Available While small bone defects heal spontaneously, large bone defects need surgical intervention for bone transplantation. Autologous bone grafts are the best and safest strategy for bone repair. An alternative method is to use allogenic bone graft. Both methods have limitations, particularly when bone defects are of a critical size. In these cases, bone constructs created by tissue engineering technologies are of utmost importance. Cells are one main component in the manufacture of bone construct. A few cell types, including embryonic stem cells (ESCs, adult osteoblast, and adult stem cells, can be used for this purpose. Mesenchymal stem cells (MSCs, as adult stem cells, possess characteristics that make them good candidate for bone repair. This paper discusses different aspects of MSCs that render them an appropriate cell type for clinical use to promote bone regeneration.

  16. Regenerative repair of damaged meniscus with autologous adipose tissue-derived stem cells.

    Science.gov (United States)

    Pak, Jaewoo; Lee, Jung Hun; Lee, Sang Hee

    2014-01-01

    Mesenchymal stem cells (MSCs) are defined as pluripotent cells found in numerous human tissues, including bone marrow and adipose tissue. Such MSCs, isolated from bone marrow and adipose tissue, have been shown to differentiate into bone and cartilage, along with other types of tissues. Therefore, MSCs represent a promising new therapy in regenerative medicine. The initial treatment of meniscus tear of the knee is managed conservatively with nonsteroidal anti-inflammatory drugs and physical therapy. When such conservative treatment fails, an arthroscopic resection of the meniscus is necessary. However, the major drawback of the meniscectomy is an early onset of osteoarthritis. Therefore, an effective and noninvasive treatment for patients with continuous knee pain due to damaged meniscus has been sought. Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs)), along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee.

  17. Viability of mesenchymal stem cells during electrospinning

    Directory of Open Access Journals (Sweden)

    G. Zanatta

    2012-02-01

    Full Text Available Tissue engineering is a technique by which a live tissue can be re-constructed and one of its main goals is to associate cells with biomaterials. Electrospinning is a technique that facilitates the production of nanofibers and is commonly used to develop fibrous scaffolds to be used in tissue engineering. In the present study, a different approach for cell incorporation into fibrous scaffolds was tested. Mesenchymal stem cells were extracted from the wall of the umbilical cord and mononuclear cells from umbilical cord blood. Cells were re-suspended in a 10% polyvinyl alcohol solution and subjected to electrospinning for 30 min under a voltage of 21 kV. Cell viability was assessed before and after the procedure by exclusion of dead cells using trypan blue staining. Fiber diameter was observed by scanning electron microscopy and the presence of cells within the scaffolds was analyzed by confocal laser scanning microscopy. After electrospinning, the viability of mesenchymal stem cells was reduced from 88 to 19.6% and the viability of mononuclear cells from 99 to 8.38%. The loss of viability was possibly due to the high viscosity of the polymer solution, which reduced the access to nutrients associated with electric and mechanical stress during electrospinning. These results suggest that the incorporation of cells during fiber formation by electrospinning is a viable process that needs more investigation in order to find ways to protect cells from damage.

  18. Modeling sarcomagenesis using multipotent mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Rene Rodriguez; Ruth Rubio; Pablo Menendez

    2012-01-01

    Because of their unique properties,multipotent mesenchymal stem cells (MSCs) represent one of the most promising adult stem cells being used worldwide in a wide array of clinical applications.Overall,compelling evidence supports the long-term safety of ex vivo expanded human MSCs,which do not seem to transform spontaneously.However,experimental data reveal a link between MSCs and cancer,and MSCs have been reported to inhibit or promote tumor growth depending on yet undefined conditions.Interestingly,solid evidence based on transgenic mice and genetic intervention of MSCs has placed these cells as the most likely cell of origin for certain sarcomas.This research area is being increasingly explored to develop accurate MSC-based models of sarcomagenesis,which will be undoubtedly valuable in providing a better understanding about the etiology and pathogenesis of mesenchymal cancer,eventually leading to the development of more specific therapies directed against the sarcoma-initiating cell.Unfortunately,still little is known about the mechanisms underlying MSC transformation and further studies are required to develop bona fide sarcoma models based on human MSCs.Here,we comprehensively review the existing MSC-based models of sarcoma and discuss the most common mechanisms leading to tumoral transformation of MSCs and sarcomagenesis.

  19. Busulfan,cyclophosphamide and etoposide as conditioning for autologous stem cell transplantation in multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    张春阳

    2013-01-01

    Objective To evaluate the efficacy and safety of dose-reduced intravenous busulfan,cyclophosphamide and etoposide(BCV)as conditioning for autologous stem cell transplantation(ASCT)in multiple myeloma(MM)

  20. Mesenchymal stem cells: cell biology and potential use in therapy

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Kristiansen, Malthe; Abdallah, Basem M

    2004-01-01

    Mesenchymal stem cells are clonogenic, non-haematopoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages e.g. osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages e.g. neuronal-like cells. Several methods...... are currently available for isolation of the mesenchymal stem cells based on their physical and immunological characteristics. Because of the ease of their isolation and their extensive differentiation potential, mesenchymal stem cells are among the first stem cell types to be introduced in the clinic. Recent...... studies have demonstrated that the life span of mesenchymal stem cells in vitro can be extended by increasing the levels of telomerase expression in the cells and thus allowing culture of large number of cells needed for therapy. In addition, it has been shown that it is possible to culture the cells...

  1. Effectiveness of autologous serum as an alternative to fetal bovine serum in adipose-derived stem cell engineering.

    Science.gov (United States)

    Choi, Jaehoon; Chung, Jee-Hyeok; Kwon, Geun-Yong; Kim, Ki-Wan; Kim, Sukwha; Chang, Hak

    2013-09-01

    In cell culture, medium supplemented with fetal bovine serum is commonly used, and it is widely known that fetal bovine serum supplies an adequate environment for culture and differentiation of stem cells. Nevertheless, the use of xenogeneic serum can cause several problems. We compared the effects of four different concentrations of autologous serum (1, 2, 5, and 10%) on expansion and adipogenic differentiation of adipose-derived stem cells using 10% fetal bovine serum as a control. The stem cells were grafted on nude mice and the in vivo differentiation capacity was evaluated. The isolation of adipose-derived stem cells was successful irrespective of the culture medium. The proliferation potential was statistically significant at passage 2, as follows: 10% autologous serum > 10% fetal bovine serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. The differentiation capacity appeared statistically significant at passage 4, as follows: 10% fetal bovine serum > 10% autologous serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. Ten percent autologous serum and 10% fetal bovine serum had greater differentiation capacity than 1 and 2% autologous serum in vivo, and no significant difference was observed between the groups at ≥ 5% concentration at 14 weeks. In conclusion, 10% autologous serum was at least as effective as 10% fetal bovine serum with respect to the number of adipose-derived stem cells at the end of both isolation and expansion, whereas 1 and 2% autologous serum was inferior.

  2. Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds.

    Science.gov (United States)

    Mygind, Tina; Stiehler, Maik; Baatrup, Anette; Li, Haisheng; Zou, Xuenong; Flyvbjerg, Allan; Kassem, Moustapha; Bünger, Cody

    2007-02-01

    Culture of osteogenic cells on a porous scaffold could offer a new solution to bone grafting using autologous human mesenchymal stem cells (hMSC) from the patient. We compared coralline hydroxyapatite scaffolds with pore sizes of 200 and 500 microm for expansion and differentiation of hMSCs. We cultivated the hMSC statically or in spinner flasks for 1, 7, 14 and 21 days and found that the 200-microm pore scaffolds exhibited a faster rate of osteogenic differentiation than did the 500-microm pore scaffolds as shown by an alkaline phosphatase activity assay and real-time reverse transcriptase polymerase chain reaction for 10 osteogenic markers. The 500-microm scaffolds had increased proliferation rates and accommodated a higher number of cells (shown by DNA content, scanning electron microscopy and fluorescence microscopy). Thus the porosity of a 3D microporous biomaterial may be used to steer hMSC in a particular direction. We found that dynamic spinner flask cultivation of hMSC/scaffold constructs resulted in increased proliferation, differentiation and distribution of cells in scaffolds. Therefore, spinner flask cultivation is an easy-to-use inexpensive system for cultivating hMSCs on small to intermediate size 3D scaffolds.

  3. Stem cells for hepatic regeneration: the role of adipose tissue derived mesenchymal stem cells.

    Science.gov (United States)

    Ishikawa, Tetsuya; Banas, Agnieszka; Hagiwara, Keitaro; Iwaguro, Hideki; Ochiya, Takahiro

    2010-06-01

    Severe hepatic dysfunctions including hepatic cirrhosis and hepatocarcinoma are life-threatening conditions for which effective medical treatments are needed. With the only effective treatment to date being orthotropic liver transplantation, alternative approaches are needed because of the limited number of donors and the possibility of immune-rejection. One alternative is regenerative medicine, which holds promise for the development of a cell-based therapy enabling hepatic regeneration through transplantation of adipose tissue-derived mesenchymal stem cells (AT-MSCs) or hepatocyte-like cells generated from AT-MSCs. When compared with embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, the use of AT-MSCs as regenerative cells would be advantageous in regard to ethical and safety issues since AT-MSCs are somatic cells and have the potential to be used without in vitro culture. These autologous cells are immuno-compatible and exhibit controlled differentiation and multi-functional abilities and do not undergo post-transplantation rejection or unwanted differentiation such as formation of teratomas. AT-MSC-based therapies may provide a novel approach for hepatic regeneration and hepatocyte differentiation and thereby support hepatic function in diseased individuals.

  4. Decreased proliferation ability and differentiation potential of mesenchymal stem cells of osteoporosis rat

    Institute of Scientific and Technical Information of China (English)

    Qiang Wang; Bing Zhao; Chao Li; Jie-Sheng Rong; Shu-Qing Tao; Tian-Zun Tao

    2014-01-01

    Objective:To explore decreased proliferation ability and differentiation potential of mesenchymal stem cells(MSCs) of osteoporosis rat.Methods:MSCs were obtained from osteoporosis rat, and proliferation potency and impaired osteogenic differentiation potential were determined. Results:The result showed a significant downregulation ofMSCs pluripotency related gene(Oct 4) and osteogenic genes(BSP,OCN) expression inOVXMSCs compared withShamMSCs(P<0.05). Conclusions:These data suggest thatMSCs are aging in osteoporosis body, and autologous OVXMSCs transplantation is not appropriate to treat osteoporosis if necessary.There will be a possibility in establishing a new clinical application ofMSCs autologous transplantation to treat osteoporosis, ifOVXMSCs have stronger proliferation and differentiation.

  5. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Francesco Orio

    2014-01-01

    Full Text Available Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo- and autologous- (auto- stem cell transplant (HSCT. This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma, gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.

  6. Autologous Intravenous Mononuclear Stem Cell Therapy in Chronic Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Bhasin A

    2012-01-01

    Full Text Available Background: The regenerative potential of brain has led to emerging therapies that can cure clinico-motor deficits after neurological diseases. Bone marrow mononuclear cell therapy is a great hope to mankind as these cells are feasible, multipotent and aid in neurofunctional gains in Stroke patients. Aims: This study evaluates safety, feasibility and efficacy of autologous mononuclear (MNC stem cell transplantation in patients with chronic ischemic stroke (CIS using clinical scores and functional imaging (fMRI and DTI. Design: Non randomised controlled observational study Study: Twenty four (n=24 CIS patients were recruited with the inclusion criteria as: 3 months–2years of stroke onset, hand muscle power (MRC grade at least 2; Brunnstrom stage of recovery: II-IV; NIHSS of 4-15, comprehendible. Fugl Meyer, modified Barthel Index (mBI and functional imaging parameters were used for assessment at baseline, 8 weeks and at 24 weeks. Twelve patients were administered with mean 54.6 million cells intravenously followed by 8 weeks of physiotherapy. Twelve patients served as controls. All patients were followed up at 24 weeks. Outcomes: The laboratory and radiological outcome measures were within normal limits in MNC group. Only mBI showed statistically significant improvement at 24 weeks (p<0.05 whereas the mean FM, MRC, Ashworth tone scores in the MNC group were high as compared to control group. There was an increased number of cluster activation of Brodmann areas BA 4, BA 6 post stem cell infusion compared to controls indicating neural plasticity. Cell therapy is safe and feasible which may facilitate restoration of function in CIS.

  7. Mesenchymal stem cells: A new diagnostic tool?

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Mesenchymal stem cells (MSCs) are progenitor cellscapable of self-renewal that can differentiate inmultiple tissues and, under specific and standardized culture conditions, expand in vitro with little phenotypicalterations. In recent years, preclinical andclinical studies have focused on MSC analysis andunderstanding the potential use of these cells as atherapy in a wide range of pathologies, and manyapplications have been tested. Clinical trials usingMSCs have been performed (e.g. , for cardiac events,stroke, multiple sclerosis, blood diseases, auto-immunedisorders, ischemia, and articular cartilage and bonepathologies), and for many genetic diseases, thesecells are considered an important resource. Consideringof the biology of MSCs, these cells may also be usefultools for understanding the physiopathology of differentdiseases, and they can be used to develop specificbiomarkers for a broad range of diseases. In thiseditorial, we discuss the literature related to the use ofMSCs for diagnostic applications and we suggest newtechnologies to improve their employment.

  8. Optimizing mesenchymal stem cell-based therapeutics.

    Science.gov (United States)

    Wagner, Joseph; Kean, Thomas; Young, Randell; Dennis, James E; Caplan, Arnold I

    2009-10-01

    Mesenchymal stem cell (MSC)-based therapeutics are showing significant benefit in multiple clinical trials conducted by both academic and commercial organizations, but obstacles remain for their large-scale commercial implementation. Recent studies have attempted to optimize MSC-based therapeutics by either enhancing their potency or increasing their delivery to target tissues. Overexpression of trophic factors or in vitro exposure to potency-enhancing factors are two approaches that are demonstrating success in preclinical animal models. Delivery enhancement strategies involving tissue-specific cytokine pathways or binding sites are also showing promise. Each of these strategies has its own set of distinct advantages and disadvantages when viewed with a mindset of ultimate commercialization and clinical utility.

  9. Mesenchymal Stem Cells: Angels or Demons?

    Directory of Open Access Journals (Sweden)

    Rebecca S. Y. Wong

    2011-01-01

    Full Text Available Mesenchymal stem cells (MSCs have been used in cell-based therapy in various disease conditions such as graft-versus-host and heart diseases, osteogenesis imperfecta, and spinal cord injuries, and the results have been encouraging. However, as MSC therapy gains popularity among practitioners and researchers, there have been reports on the adverse effects of MSCs especially in the context of tumour modulation and malignant transformation. These cells have been found to enhance tumour growth and metastasis in some studies and have been related to anticancer-drug resistance in other instances. In addition, various studies have also reported spontaneous malignant transformation of MSCs. The mechanism of the modulatory behaviour and the tumorigenic potential of MSCs, warrant urgent exploration, and the use of MSCs in patients with cancer awaits further evaluation. However, if MSCs truly play a role in tumour modulation, they can also be potential targets of cancer treatment.

  10. Potential use of mesenchymal stem cells in human meniscal repair: current insights

    Science.gov (United States)

    Pak, Jaewoo; Lee, Jung Hun; Park, Kwang Seung; Jeon, Jeong Ho; Lee, Sang Hee

    2017-01-01

    The menisci of the human knee play an important role in maintaining normal functions to provide stability and nutrition to the articular cartilage, and to absorb shock. Once injured, these important structures have very limited natural healing potential. Unfortunately, the traditional arthroscopic meniscectomy performed on these damaged menisci may predispose the joint toward early development of osteoarthritis. Although a very limited number of studies are available, mesenchymal stem cells (MSCs) have been investigated as an alternative therapeutic modality to repair human knee meniscal tears. This review summarizes the results of published applications of MSCs in human patients, which showed that the patients who received MSCs (autologous adipose tissue-derived stem cells or culture-expanded bone marrow-derived stem cells) presented symptomatic improvements, along with magnetic resonance imaging evidences of the meniscal repair. PMID:28356779

  11. Application of Nanoscaffolds in Mesenchymal Stem Cell-Based Therapy

    OpenAIRE

    Ghoraishizadeh, Saman; Ghorishizadeh, Afsoon; Ghoraishizadeh, Peyman; Daneshvar,Nasibeh; Boroojerdi, Mohadese Hashem

    2014-01-01

    Regenerative medicine is an alternative solution for organ transplantation. Stem cells and nanoscaffolds are two essential components in regenerative medicine. Mesenchymal stem cells (MSCs) are considered as primary adult stem cells with high proliferation capacity, wide differentiation potential, and immunosuppression properties which make them unique for regenerative medicine and cell therapy. Scaffolds are engineered nanofibers that provide suitable microenvironment for cell signalling whi...

  12. Comparison of different culture conditions for human mesenchymal stromal cells for clinical stem cell therapy

    DEFF Research Database (Denmark)

    Haack-Sorensen, M.; Friis, T.; Bindslev, L.

    2008-01-01

    used for MSC cultivation in animal studies simulating clinical stem cell therapy. MATERIAL AND METHODS: Human mononuclear cells (MNCs) were isolated from BM aspirates by density gradient centrifugation and cultivated in a GMP-accepted medium (EMEA medium) or in one of four other media. RESULTS: FACS...... compliant medium for MSC cultivation, expansion and differentiation. The expanded and differentiated MSCs can be used in autologous mesenchymal stromal cell therapy in patients with ischaemic heart disease Udgivelsesdato: 2008......OBJECTIVE: Mesenchymal stromal cells (MSCs) from adult bone marrow (BM) are considered potential candidates for therapeutic neovascularization in cardiovascular disease. When implementing results from animal trials in clinical treatment, it is essential to isolate and expand the MSCs under...

  13. Labeling and Imaging Mesenchymal Stem Cells with Quantum Dots

    Science.gov (United States)

    Mesenchymal stem cells (MSCs) are multipotent cells with the potential to differentiate into bone, cartilage, adipose and muscle cells. Adult derived MSCs are being actively investigated because of their potential to be utilized for therapeutic cell-based transplantation. Methods...

  14. AUTOTRANSPLANTATION OF MESENCHYMAL STEM CELLS FROM ADIPOSE TISSUE – INNOVATIVE PATHOGENETIC METHOD OF TREATMENT OF PATIENTS WITH INCISIONAL HERNIAS (FIRST CASES REPORT

    Directory of Open Access Journals (Sweden)

    V. G. Bogdan

    2012-01-01

    Full Text Available In the article a complex technology of receiving a biological transplant with autologous mesenchymal stem cells from the adipose tissue is presented. Possibility of successful clinical performance of reconstruction of extensive defects of anterior belly wall with the use of a multicomponent biological transplant with autologous mesenchy- mal stem cells from the adipose tissue, differentiated in the fibroblast direction is shown. The use of the proposed method of plasticity promotes the improvement of quality of surgical treatment, expansies the scope of cellular technologies in practical health care, improves the patients quality of life in the postoperative period. 

  15. Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation

    Science.gov (United States)

    2015-09-01

    1 AWARD NUMBER: W81XWH-11-1-0666 TITLE: Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation PRINCIPAL INVESTIGATOR...4Aug2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-1-0666 Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation 5b...in a well-characterized mouse model of chronic colonic inflammation . Hypothesis: We propose that ex vivo-generated MSCs suppress chronic gut

  16. Mesenchymal stem cells: characteristics and clinical applications.

    Directory of Open Access Journals (Sweden)

    Sylwia Bobis

    2007-01-01

    Full Text Available Mesenchymal stem cells (MSCs are bone marrow populating cells, different from hematopoietic stem cells, which possess an extensive proliferative potential and ability to differentiate into various cell types, including: osteocytes, adipocytes, chondrocytes, myocytes, cardiomyocytes and neurons. MSCs play a key role in the maintenance of bone marrow homeostasis and regulate the maturation of both hematopoietic and non-hematopoietic cells. The cells are characterized by the expression of numerous surface antigens, but none of them appears to be exclusively expressed on MSCs. Apart from bone marrow, MSCs are located in other tissues, like: adipose tissue, peripheral blood, cord blood, liver and fetal tissues. MSCs have been shown to be powerful tools in gene therapies, and can be effectively transduced with viral vectors containing a therapeutic gene, as well as with cDNA for specific proteins, expression of which is desired in a patient. Due to such characteristics, the number of clinical trials based on the use of MSCs increase. These cells have been successfully employed in graft versus host disease (GvHD treatment, heart regeneration after infarct, cartilage and bone repair, skin wounds healing, neuronal regeneration and many others. Of special importance is their use in the treatment of osteogenesis imperfecta (OI, which appeared to be the only reasonable therapeutic strategy. MSCs seem to represent a future powerful tool in regenerative medicine, therefore they are particularly important in medical research.

  17. Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: perspectives from stem cell biology and molecular medicine.

    Science.gov (United States)

    Wu, Ling; Cai, Xiaoxiao; Zhang, Shu; Karperien, Marcel; Lin, Yunfeng

    2013-05-01

    Adipose-derived stem cells (ASCs) have been discovered for more than a decade. Due to the large numbers of cells that can be harvested with relatively little donor morbidity, they are considered to be an attractive alternative to bone marrow derived mesenchymal stem cells. Consequently, isolation and differentiation of ASCs draw great attention in the research of tissue engineering and regenerative medicine. Cartilage defects cause big therapeutic problems because of their low self-repair capacity. Application of ASCs in cartilage regeneration gives hope to treat cartilage defects with autologous stem cells. In recent years, a lot of studies have been performed to test the possibility of using ASCs to re-construct damaged cartilage tissue. In this article, we have reviewed the most up-to-date articles utilizing ASCs for cartilage regeneration in basic and translational research. Our topic covers differentiation of adipose tissue derived mesenchymal stem cells into chondrocytes, increased cartilage formation by co-culture of ASCs with chondrocytes and enhancing chondrogenic differentiation of ASCs by gene manipulation.

  18. Radiation response of mesenchymal stem cells derived from bone marrow and human pluripotent stem cells

    OpenAIRE

    Islam, Mohammad S; Stemig, Melissa E.; Takahashi, Yutaka; Hui, Susanta K.

    2014-01-01

    Mesenchymal stem cells (MSCs) isolated from human pluripotent stem cells are comparable with bone marrow-derived MSCs in their function and immunophenotype. The purpose of this exploratory study was comparative evaluation of the radiation responses of mesenchymal stem cells derived from bone marrow- (BMMSCs) and from human embryonic stem cells (hESMSCs). BMMSCs and hESMSCs were irradiated at 0 Gy (control) to 16 Gy using a linear accelerator commonly used for cancer treatment. Cells were harv...

  19. Membranous nephropathy in autologous hematopoietic stem cell transplant: autologous graft-versus-host disease or autoimmunity induction?

    Science.gov (United States)

    Abudayyeh, Ala; Truong, Luan D.; Beck, Laurence H.; Weber, Donna M.; Rezvani, Katy; Abdelrahim, Maen

    2015-01-01

    With the increasing utility of hematopoietic stem cell transplantation (SCT) as a treatment for cancer and noncancerous disorders, more challenges and complications associated with SCT have emerged. Renal injury immediately after transplant is common and well understood, but long-term renal injury is becoming more evident. Chronic graft-versus-host disease (GVHD) is a known long-term complication of SCT, and membranous nephropathy (MN) is emerging as the most common cause of SCT-associated glomerular pathology. In this case report, we present a patient who developed features of anti-PLA2R antibody-negative MN following autologous SCT. The renal injury responded well to steroids and further response to rituximab therapy was noted, suggesting antibody-mediated autoimmune glomerular disease. We also present a review of the literature on autologous GVHD and the role of T and B cells in induction of autoimmunity by SCT. PMID:26251713

  20. Hepatitis B-related events in autologous hematopoietic stem cell transplantation recipients

    Institute of Scientific and Technical Information of China (English)

    zcan; eneli; Zübeyde; Nur; zkurt; Kadir; Acar; Seyyal; Rota; Sahika; Zeynep; Aki; Zeynep; Arzu; Yegin; Münci; Yagci; Seren; zenirler; Gülsan; Türkz; Sucak

    2010-01-01

    AIM: To investigate the frequency of occult hepatitis B, the clinical course of hepatitis B virus (HBV) reactivation and reverse seroconversion and associated risk factors in autologous hematopoietic stem cell transplantation (HSCT) recipients. METHODS: This study was conducted in 90 patients undergoing autologous HSCT. Occult HBV infection was investigated by HBV-DNA analysis prior to transplantation, while HBV serology and liver function tests were screened prior to and serially after transplantation. HBV...

  1. HORSE SPECIES SYMPOSIUM: Use of mesenchymal stem cells in fracture repair in horses.

    Science.gov (United States)

    Govoni, K E

    2015-03-01

    Equine bone fractures are often catastrophic, potentially fatal, and costly to repair. Traditional methods of healing fractures have limited success, long recovery periods, and a high rate of reinjury. Current research in the equine industry has demonstrated that stem cell therapy is a promising novel therapy to improve fracture healing and reduce the incidence of reinjury; however, reports of success in horses have been variable and limited. Stem cells can be derived from embryonic, fetal, and adult tissue. Based on the ease of collection, opportunity for autologous cells, and proven success in other models, adipose- or bone marrow-derived mesenchymal stem cells (MSC) are often used in equine therapies. Methods for isolation, proliferation, and differentiation of MSC are well established in rodent and human models but are not well characterized in horses. There is recent evidence that equine bone marrow MSC are able to proliferate in culture for several passages in the presence of autologous and fetal bovine serum, which is important for expansion of cells. Mesenchymal stem cells have the capacity to differentiate into osteoblasts, the bone forming cells, and this complex process is regulated by a number of transcription factors including runt-related transcription factor 2 (Runx2) and osterix (Osx). However, it has not been well established if equine MSC are regulated in a similar manner. The data presented in this review support the view that equine bone marrow MSC are regulated by the same transcription factors that control the differentiation of rodent and human MSC into osteoblasts. Although stem cell therapy is promising in equine bone repair, additional research is needed to identify optimal methods for reintroduction and potential manipulations to improve their ability to form new bone.

  2. Telomere stability and telomerase in mesenchymal stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Graakjaer, Jesper; Kølvrå, Steen

    2008-01-01

    Telomeres are repetitive genetic material that cap and thereby protect the ends of chromosomes. Each time a cell divides, telomeres get shorter. Telomere length is mainly maintained by telomerase. This enzyme is present in high concentrations in the embryonic stem cells and in fast growing...... embryonic cells, and declines with age. It is still unclear to what extent there is telomerase in adult stem cells, but since these are the founder cells of cells of all the tissues in the body, understanding the telomere dynamics and expression of telomerase in adult stem cells is very important....... In the present communication we focus on telomere expression and telomere length in stem cells, with a special focus on mesenchymal stem cells. We consider different mechanisms by which stem cells can maintain telomeres and also focus on the dynamics of telomere length in mesenchymal stem cells, both the overall...

  3. 自体脂肪源性间充质干细胞局部移植对兔耳增生性瘢痕形成的影响%Effects of local transplantation of autologous adipose-derived mesenchymal stem cells on the formation of hyperplastic scar on rabbit ears

    Institute of Scientific and Technical Information of China (English)

    陈璐; 王达利; 魏在荣; 王波; 祁建平; 孙广峰

    2016-01-01

    Objective To investigate the effects of local transplantation of autologous adipose-derived mesenchymal stem cells (ADSCs) on the formation of hyperplastic scar on rabbit ears.Methods ADSCs were isolated from inguinal fat of six New Zealand rabbits and then sub-cultured.ADSCs of the third passage of each rabbit were used in the following experiments.Six full-thickness skin defect wounds with diameter of 6 mm on the ventral surface of every rabbit ear were made.Wound healing and local-tissue proliferation were observed,and complete epithelization time of wounds and formation time of hyperplastic scar were recorded.The wounds on left ears were selected as group ADSCs,and the wounds on right ears were selected as control group,with 36 wounds in each group.After the complete epithelization of wounds (post injury day 25),0.2 mL bromodeoxyuridine (BrdU) labeled autologous ADSCs with the concentration of 5 ×106 per milliliter were injected into each wound of the rabbit of group ADSCs,while the same amount of phosphate buffer solution was injected into each wound of the rabbit of control group.The frequency of injection was once every 5 days,totally for 3 times,and the latter 2 times were injected into scars generated from healed wound.Hyperplastic scars of rabbits of two groups were harvested on the fifth day after the third injection,then the morphology was observed by HE staining,and the arrangement of collagen in hyperplastic scar was observed by VG staining.The distribution of BrdU-labeled ADSCs in the hyperplastic scar was observed with fluorescence microscope.The protein content of type Ⅰ collagen,type Ⅲ collagen,transforming growth factor β1 (TGF-β1),and decorin in hyperplastic scar were detected by enzyme-linked immunosorbent assay,and the mRNA expression of decorin and TGF-β1 in hyperplastic scar were tested by real-time fluorescent quantitative reverse transcription-polymerase chain reaction.Data were processed with paired t test.Results (1) The complete

  4. Mesenchymal stem cell implantation in atrophic nonunion of the long bones

    Science.gov (United States)

    Phedy, P.; Kholinne, E.; Djaja, Y. P.; Kusnadi, Y.; Merlina, M.; Yulisa, N. D.

    2016-01-01

    Objectives To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone. Methods Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm3 (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm3 HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment. Results Post-operative pain evaluation showed no significant differences between the two groups. The treatment group demonstrated faster initial radiographic and functional improvements. Statistically significant differences in functional scores were present during the first (p = 0.002), second (p = 0.005) and third (p = 0.01) month. Both groups achieved similar outcomes by the end of one-year follow-up. No immunologic or neoplastic side effects were reported. Conclusions All cases of nonunion of a long bone presented in this study were successfully treated using autologous BM-MSCs. The combination of autologous BM-MSCs and HA granules is a safe method for treating nonunion. Patients treated with BM-MSCs had faster initial radiographic and functional improvements. By the end of 12 months, both groups had similar outcomes. Cite this article: H.D. Ismail, P. Phedy, E. Kholinne, Y. P. Djaja, Y. Kusnadi, M. Merlina, N. D. Yulisa. Mesenchymal stem cell implantation in atrophic nonunion of the long bones: A translational study. Bone Joint Res 2016;5:287–293. DOI: 10.1302/2046-3758.57.2000587. PMID:27412657

  5. Exosomes Derived from Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Bo Yu

    2014-03-01

    Full Text Available The functional mechanisms of mesenchymal stem cells (MSCs have become a research focus in recent years. Accumulating evidence supports the notion that MSCs act in a paracrine manner. Therefore, the biological factors in conditioned medium, including exosomes and soluble factors, derived from MSC cultures are being explored extensively. The results from most investigations show that MSC-conditioned medium or its components mediate some biological functions of MSCs. Several studies have reported that MSC-derived exosomes have functions similar to those of MSCs, such as repairing tissue damage, suppressing inflammatory responses, and modulating the immune system. However, the mechanisms are still not fully understood and the results remain controversial. Compared with cells, exosomes are more stable and reservable, have no risk of aneuploidy, a lower possibility of immune rejection following in vivo allogeneic administration, and may provide an alternative therapy for various diseases. In this review, we summarize the properties and biological functions of MSC-derived exosomes and discuss the related mechanisms.

  6. Mesenchymal stem cells: from experiment to clinic

    Directory of Open Access Journals (Sweden)

    Otto William R

    2011-09-01

    Full Text Available Abstract There is currently much interest in adult mesenchymal stem cells (MSCs and their ability to differentiate into other cell types, and to partake in the anatomy and physiology of remote organs. It is now clear these cells may be purified from several organs in the body besides bone marrow. MSCs take part in wound healing by contributing to myofibroblast and possibly fibroblast populations, and may be involved in epithelial tissue regeneration in certain organs, although this remains more controversial. In this review, we examine the ability of MSCs to modulate liver, kidney, heart and intestinal repair, and we update their opposing qualities of being less immunogenic and therefore tolerated in a transplant situation, yet being able to contribute to xenograft models of human tumour formation in other contexts. However, such observations have not been replicated in the clinic. Recent studies showing the clinical safety of MSC in several pathologies are discussed. The possible opposing powers of MSC need careful understanding and control if their clinical potential is to be realised with long-term safety for patients.

  7. Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix

    Directory of Open Access Journals (Sweden)

    Jaewoo Pak

    2016-08-01

    Full Text Available This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs and homogenized extracellular matrix (ECM in the form of adipose stromal vascular fraction (SVF, along with hyaluronic acid (HA and platelet-rich plasma (PRP activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI data, functional rating index, range of motion (ROM, and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees.

  8. Autologous CD34~+ and CD133~+ stem cells transplantation in patients with end stage liver disease

    Institute of Scientific and Technical Information of China (English)

    Hosny; Salama; Abdel-Rahman; N; Zekri; Abeer; A; Bahnassy; Eman; Medhat; Hanan; A; Halim; Ola; S; Ahmed; Ghada; Mohamed; Sheren; A; Al; Alim; Ghada; M; Sherif

    2010-01-01

    AIM:To assess the utility of an autologous CD34 + and CD133 + stem cells infusion as a possible therapeutic modality in patients with end-stage liver diseases.METHODS:One hundred and forty patients with endstage liver diseases were randomized into two groups.Group 1,comprising 90 patients,received granulocyte colony stimulating factor for five days followed by autologous CD34 + and CD133 + stem cell infusion in the portal vein.Group 2,comprising 50 patients,received regular liver treatment only and served a...

  9. Autologous stem cell transplantation as first line treatment after incomplete excision of pancreatoblastoma.

    Science.gov (United States)

    Meneses, Clarice Franco; Osório, Carolina Dame; de Castro Junior, Claudio Galvão; Brunetto, Algemir Lunardi

    2013-01-01

    Pancreatoblastoma is a rare tumor and surgery with complete resection is the main treatment approach. Prognosis for patients with residual disease after surgery is usually dismal. A 14-year-old girl with pancreatoblastoma in the pancreatic body and tail was submitted to preoperative chemotherapy. She underwent surgery and the tumor was resected with microscopic margins. Postoperative chemotherapy was followed by high dose chemotherapy and autologous hematopoietic stem cell transplantation. After four years she remains very well with no evidence of disease. This is the first case reported of pancreatoblastoma that was treated with autologous hematopoietic stem cell transplantation as first line treatment without radiotherapy at the site of the microscopic disease.

  10. Autologous Bone Marrow Stem Cell Infusion (AMBI therapy for Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Rajkumar JS

    2007-01-01

    Full Text Available Liver Cirrhosis is the end stage of chronic liver disease which may happen due to alcoholism, viral infections due to Hepatitis B, Hepatitis C viruses and is difficult to treat. Liver transplantation is the only available definitive treatment which is marred by lack of donors, post operative complications such as rejection and high cost. Autologous bone marrow stem cells have shown a lot of promise in earlier reported animal studies and clinical trials. We have in this study administered in 22 patients with chronic liver disease, autologous bone marrow stem cell whose results are presented herewith.

  11. Comparison of the effects of human mesenchymal stem cells cultured by autologous serum into osteoblasts by extracorporeal shock waves versus dexamethasone%冲击波与地塞米松对自体血清培养的骨髓间充质干细胞成骨分化的比较研究

    Institute of Scientific and Technical Information of China (English)

    安佰京; 邢更彦

    2011-01-01

    [目的]观察冲击波(shock waves)与地塞米松对自体血清培养的人骨髓间充质干细胞(human mesenchyreal stem cells,hMSCs)体外成骨分化的影响比较.[方法]选择10名健康志愿者,每名健康志愿者抽取骨髓60 ml,抽取外周静脉血100 ml,然后分离出自体血清.把每名志愿者的骨髓分别用10%AS和10%FBS对hMSCs进行体外培养,通过相差倒置显微镜观察细胞形态、检测24 h细胞贴壁率、细胞倍增时间、检测细胞表面标记物、细胞周期及免疫细胞化学染色检测比较两组hMSCs的增殖状况.然后把AS培养的hMSCs两组分别用体外冲击波疗法(extracorporeal shock waves therapy,ESWT)[0.36 mj/(mm·100次)]和传统的诱导成骨培养基(10 nmol/L地寒米松、50umol/L抗坏血酸、10 mmol/L β-甘油磷酸钠)分别对hMSCs进行成骨诱导,对诱导好的细胞进行ALP定量检测、ALP染色、茜素红染色及RT-PCR测成骨基因(碱性磷酸酶、骨钙素、骨桥蛋白、骨结合素、Ⅰ型胶原)表达比较两组成骨分化情况.[结果]在细胞增殖上,两组细胞各代在细胞形态、细胞贴壁率、细胞周期以及免疫细胞化学染色检测上无明显差异,但在细胞倍增时间、细胞增殖速率上,自体血清明显优于胎牛血清.在细胞分化方面,两组在ALP定量检测、ALP染色、茜素红染色及RT-PCR测成骨基因上,冲击波作用于人骨髓间充质干细胞的成骨效应明显优于地塞米松.[结论]冲击波与地塞米松相比较,具有更良好促hMSCs成骨分化作用.%[Objective]To compare effects on the osteoblasts of human mesenchymal stem cells (hMSCs) in autologous serum by extracorporeal shock waves versus dexamethasone.[Methods]60 ml iliac crest bone marrow and 100 ml peripheral blood from 10 healthy volunteers were collected and the autologous serum were from peripheral blood.The iliac crest bone marrow from each volunteer were cultured for hMSCs with 10% AS (the experiment group

  12. MRI assessment of acute myocardial infarction with transplantation of autologous mesenchymal stem cells in swine:an experimental study%MRI评价骨髓问质干细胞治疗猪急性心肌梗死效果的实验研究

    Institute of Scientific and Technical Information of China (English)

    陆敏杰; 赵世华; 钱海燕; 蒋世良; 韦云青; 闫朝武; 杨跃进; 刘玉清

    2008-01-01

    目的 应用MRI评价经冠状动脉途径移植猪自体骨髓间质干细胞(BM-MSCs)治疗急性心肌梗死(AMI)的治疗效果.方法 8月龄中华小型猪14只[(27±3)kg],平均分成移植组与对照组.胶圈套扎左前降支第一对角支分叉以远90 min后松开,建成AMI模型.心肌梗死后1周进行细胞移植,将干细胞悬液(移植组:1×106/ml × 10 ml)或无血清培养液(DMEM)(对照组10 ml)经微导管注入前降支.AMI术后1周(基线)和MSCs移植后6周(终点)各行1次MR扫描,评价移植前后心脏形态、功能、心肌灌注及延迟增强.第2次MR扫描后立即处死动物,分别行冰冻切片、石蜡切片和电镜观察.结果 与对照组比较,移植组在移植6周后左心室整体功能较前明显改善,实验组与对照组比较,左心室平均射血分数(EF)值从(42.7±7.5)%升至(50.1±10.1)%(P<0.01),左心室节段运动异常数平均减少4个(P<0.01)、梗死面积减少3.2 cm2(P<0.01),心脏重量指数增加4.1 g/m2(P<0.05).病理证实移植组梗死区和梗死周边的病变情况显著轻于对照组,有大量存活心肌,纤维化程度显著减轻;并且可见核大、边集,胞质丰富的幼稚细胞;在梗死区和梗死周边区组织的冰冻切片上可见4-6-二脒基二苯基吲哚(DAPI)阳性的移植细胞存活.免疫荧光检测进一步表明大部分DAPI阳性细胞表达心肌特异性肌钙蛋白T(troponin T),并且表达间隙连接蛋白43(connexin 43).部分DAPI阳性细胞表达平滑肌肌动蛋白(smooth muscle actin)和血管性血友病因子(Von Willebrand),移植组梗死周边区毛细血管密度显著高于对照组[分别为(8.7±2.0)、(4.9±1.3)个/高倍镜](P<0.01).结论 MRI可作为猪BM-MSCs在体移植前后评价其治疗效果的可靠影像检查方法 .%Objective To investigate the effects of autologous bone marrow-derived mesenchymal stem cells (MSCs)transplantation on acute myocardial infarction in swine models using MRI. Methods

  13. Untested, unproven, and unethical: the promotion and provision of autologous stem cell therapies in Australia.

    Science.gov (United States)

    McLean, Alison K; Stewart, Cameron; Kerridge, Ian

    2015-02-09

    An increasing number of private clinics in Australia are marketing and providing autologous stem cell therapies to patients. Although advocates point to the importance of medical innovation and the primacy of patient choice, these arguments are unconvincing. First, it is a stark truth that these clinics are flourishing while the efficacy and safety of autologous stem cell therapies, outside of established indications for hematopioetic stem cell transplantation, are yet to be shown. Second, few of these therapies are offered within clinical trials. Third, patients with chronic and debilitating illnesses, who are often the ones who take up these therapies, incur significant financial burdens in the expectation of benefiting from these treatments. Finally, the provision of these stem cell therapies does not follow the established pathways for legitimate medical advancement. We argue that greater regulatory oversight and professional action are necessary to protect vulnerable patients and that at this time the provision of unproven stem cell therapies outside of clinical trials is unethical.

  14. Impact of autologous bone marrow mesenchymal stem cell mobilization on neurological function recovery after minimally invasive surgery with cerebral hemorrhage%脑出血微创术后自体骨髓间充质干细胞动员对神经功能恢复的影响

    Institute of Scientific and Technical Information of China (English)

    胡炜; 胡维; 杨枫

    2014-01-01

    目的:观察脑出血大鼠微创术后骨髓间充质干细胞(BMSCs)动员对神经功能的影响。方法将45只大鼠建立脑出血模型后,随机分为两组,对照组(n=20,行微创引流手术)和治疗组(n=25,微创引流手术后3~5 d开始BMSCs动员)。术前当天及术后2、4、8周行Garcia神经功能量表评分,术前当天、术后2周测定外周血CD133+、CD34+细胞数,术前及术后2、4、8周行肝肾功能检查。结果两组术后Garcia量表分值均显著高于术前(P<0.05),治疗组术后各时间点Garcia神经功能量表分值显著高于对照组(P<0.05)。术后2周,治疗组外周血CD133+、CD34+细胞在单核细胞(MNCs)中的比例明显高于对照组(P<0.05)。BMSCs 动员后肝肾功能检查指标均正常。结论大鼠脑出血微创术后早期进行 BMSCs 动员,没有肝肾功能损伤,并可促进神经功能恢复。%Objective To observe the impact of autologous bone marrow mesenchymal stem cells (BMSCs) mobilization on neurological function recovery after cerebral hemorrhage minimally invasive surgery in rats.Methods After experimental intracerebral hemorrhage models was established, 45 SD rats were divided into two groups randomly, control group rats (20 rats, minimal invasive hematoma aspiration after modeling) and treated group (25 rats, begin BMSCs mobilization after aspiration 3-5 days). Garcia scales were performed at pre-modeling and 1, 4, 8 weeks post aspiration, CD133+, CD34+cell counts were measured in peripheral blood at pre-modeling and 2 weeks post aspiration, liver and renal function were performed in each group at 1, 3 months post BMSCs mobilization.Results Postoperative Garcia scores were significantly higher than those preoperative (P<0.05) in two groups, postoperative Garcia scores in treated group were significantly higher (P<0.05) than those in control group. Two weeks postoperation, the proportion of CD133+, CD34+ cells in

  15. The Use Of Laser Irradiation To Stimulate Adipose Derived Stem Cell Proliferation And Differentiation For Use In Autologous Grafts

    Science.gov (United States)

    Abrahamse, Heidi

    2009-09-01

    Stem cells are characterized by the qualities of self-renewal, long term viability, and the ability to differentiate into various cell types. Historically, stem cells have been isolated from the inner cell mass of blastocysts and harvesting these cells resulted in the death of the embryo leading to religious, political and ethical issues. The identification and subsequent isolation of adult stem cells from bone marrow stroma have been welcomed as an alternate source for stem cells. The clinical use of Mesenchymal Stem Cells (MSCs) presented problems such as limited cell number, pain and morbidity upon isolation. Adipose tissue is derived from the mesenchyme, is easily isolated, a reliable source of stem cells and able to differentiate into different cell types including smooth muscle. Over the past few years, the identification and characterization of stem cells has led the potential use of these cells as a promising alternative to cell replacement therapy. Smooth muscle is a major component of human tissues and is essential for the normal functioning of many different organs. Low intensity laser irradiation has been shown to increase viability, protein expression and migration of stem cells in vitro, and to stimulate proliferation of various types of stem cells. In addition, the use of laser irradiation to stimulate differentiation in the absence of growth factors has also been demonstrated in normal human neural progenitor cells (NHNPCs) in vitro where NHNPCs are not only capable of being sustained by light in the absence of growth factors, but that they are also able to differentiate normally as assessed by neurite formation. Our work has focused on the ability of laser irradiation to proliferate adipose derived stem cells (ADSCs), maintain ADSC character and increase the rate and maintenance of differentiation of ADSCs into smooth muscle and skin fibroblast cells. Current studies are also investigating the effect of different irradiation wavelengths and

  16. Efficacy of autologous transplantation of bone marrow derived mesenchymal stem cells in the treatment of decompensated liver cirrhosis%自体骨髓间充质干细胞移植治疗失代偿期肝硬化的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    吴锋; 蒲春文; 张勇

    2015-01-01

    Objective To explore the therapeutic efficacy and safety of autologous transplantation of bone marrow (BM) derived mesenchymal stem cells (BMSCs) in the treatment of decompensated liver cirrhosis. Methods Total of 17 patients with decompensated live cirrhosis were enrolled in the study. About 200 ml BM was obtained from each patient to isolate the MSCs. The BMSCS were isolated and purified by the density centrifugation method in our stem cell laboratory. The purified BMSCs (20 ml, suspended in normal saline) were transplanted into the liver via left hepatic artery. The improvement in symptoms, signs, and blood biochemistry were observed. Results Four weeks after transplantation, 16 (94.1%) patients showed improvement in fatigue, 14 (82.4%) patients had better appetite, and for 12 (70.5%) patients, the ascites decreased or disappeared after one year. No serious adverse reactions and serious postoperative complications occurred. There was a significant decrease in the serum levels of ALT and AST 8 weeks after transplantation (P = 0.0093, 0.0173). Twelve weeks after transplantation, there was significant improvement in the levels of albumin (ALB), cholinesterase (CHE), prothrombin time (PT), prothrombin activity (PTA) and fibrinogen (FIB) (P = 0.039, 0.028, 0.034, 0.041, 0.031, respectively). However, no significant changes were found in serum bilirubin level and the percentage of CD3, CD4, and CD8 (P = 0.895). One year after MSC transplantation, there was a significant improvement in the severity of fibrosis as indicated by improved hepatic fibrosis markers (P = 0.016, 0.049, 0.028, 0.021, respectively). One months after treatment, there was a decrease in the oblique occipital frontal diameter of the hepatic left lobe, and an increase in the superior inferior diameter of the hepatic left lobe by the ultrasonic examination (P = 0.0451, 0.0428). However, the oblique occipital frontal diameter of the right hepatic lobe showed no significant changes. Six months after

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

    Science.gov (United States)

    Zhu, Wenjing; Sun, Haobo; Lyu, Guozhong

    2015-12-01

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

  18. Mesenchymal stem cell-mediated functional tooth regeneration in swine.

    Directory of Open Access Journals (Sweden)

    Wataru Sonoyama

    Full Text Available Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla. Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.

  19. Mesenchymal stem cell-mediated functional tooth regeneration in swine.

    Science.gov (United States)

    Sonoyama, Wataru; Liu, Yi; Fang, Dianji; Yamaza, Takayoshi; Seo, Byoung-Moo; Zhang, Chunmei; Liu, He; Gronthos, Stan; Wang, Cun-Yu; Wang, Songlin; Shi, Songtao

    2006-12-20

    Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.

  20. Tumourigenicity and radiation resistance of mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo Peder; Horsman, Michael Robert; Kassem, Moustapha

    2012-01-01

    Background. Cancer stem cells are believed to be more radiation resistant than differentiated tumour cells of the same origin. It is not known, however, whether normal nontransformed adult stem cells share the same radioresistance as their cancerous counterpart. Material and methods....... Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under...... the intercellular matrix. These results also indicate that cancer stem cells are more radiation resistant than stem cells of the same origin....

  1. Repair of large full-thickness cartilage defect by activating endogenous peripheral blood stem cells and autologous periosteum flap transplantation combined with patellofemoral realignment.

    Science.gov (United States)

    Fu, Wei-Li; Ao, Ying-Fang; Ke, Xiao-Yan; Zheng, Zhuo-Zhao; Gong, Xi; Jiang, Dong; Yu, Jia-Kuo

    2014-03-01

    Minimal-invasive procedure and one-step surgery offer autologous mesenchymal stem cells derived from peripheral blood (PB-MSCs) a promising prospective in the field of cartilage regeneration. We report a case of a 19-year-old male athlete of kickboxing with ICRS grade IV chondral lesions at the 60° region of lateral femoral trochlea, which was repaired by activating endogenous PB-MSCs plus autologous periosteum flap transplantation combined with correcting the patellofemoral malalignment. After a 7.5 year follow-up, the result showed that the patient returned to competitive kickboxing. Second-look under arthroscopy showed a smooth surface at 8 months postoperation. The IKDC 2000 subjective score, Lysholm score and Tegner score were 95, 98 and 9 respectively at the final follow up. CT and MRI evaluations showed a significant improvement compared with those of pre-operation.

  2. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up

    NARCIS (Netherlands)

    Bjorkstrand, B.; Iacobelli, S.; Hegenbart, U.; Gruber, A.; Greinix, H.; Volin, L.; Narni, F.; Musto, P.; Beksac, M.; Bosi, A.; Milone, G.; Corradini, P.; Goldschmidt, H.; Witte, T.J.M. de; Morris, C.; Niederwieser, D.; Gahrton, G.

    2011-01-01

    PURPOSE: Results of allogeneic stem-cell transplantation (allo) in myeloma are controversial. In this trial autologous stem-cell transplantation (auto) followed by reduced-intensity conditioning matched sibling donor allo (auto-allo) was compared with auto only in previously untreated multiple myelo

  3. Quantum dot labeling of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Cascio Wayne E

    2007-11-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs are multipotent cells with the potential to differentiate into bone, cartilage, fat and muscle cells and are being investigated for their utility in cell-based transplantation therapy. Yet, adequate methods to track transplanted MSCs in vivo are limited, precluding functional studies. Quantum Dots (QDs offer an alternative to organic dyes and fluorescent proteins to label and track cells in vitro and in vivo. These nanoparticles are resistant to chemical and metabolic degradation, demonstrating long term photostability. Here, we investigate the cytotoxic effects of in vitro QD labeling on MSC proliferation and differentiation and use as a cell label in a cardiomyocyte co-culture. Results A dose-response to QDs in rat bone marrow MSCs was assessed in Control (no-QDs, Low concentration (LC, 5 nmol/L and High concentration (HC, 20 nmol/L groups. QD yield and retention, MSC survival, proinflammatory cytokines, proliferation and DNA damage were evaluated in MSCs, 24 -120 hrs post QD labeling. In addition, functional integration of QD labeled MSCs in an in vitro cardiomyocyte co-culture was assessed. A dose-dependent effect was measured with increased yield in HC vs. LC labeled MSCs (93 ± 3% vs. 50% ± 15%, p 90% of QD labeled cells were viable in all groups, however, at 120 hrs increased apoptosis was measured in HC vs. Control MSCs (7.2% ± 2.7% vs. 0.5% ± 0.4%, p Conclusion Fluorescent QDs label MSC effectively in an in vitro co-culture model. QDs are easy to use, show a high yield and survival rate with minimal cytotoxic effects. Dose-dependent effects suggest limiting MSC QD exposure.

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  1. File list: Unc.Oth.05.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

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    Lifescience Database Archive (English)

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  4. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma

    DEFF Research Database (Denmark)

    d'Amore, Francesco; Relander, Thomas; Lauritzsen, Grete F;

    2012-01-01

    Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large p...

  5. Autologous stem cell transplantation in treatment of aggressive non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, Hanneke

    2002-01-01

    There is no doubt that autologous stem cell transplantation is useful for patients with relapsed aggressive non-Hodgkin's lymphoma if they are responsive to the chemotherapy given before the transplantation. A small subset of patients with primary refractory disease still profits from this high dose

  6. Severe encephalopathy after high-dose chemotherapy with autologous stem cell support for brain tumours.

    NARCIS (Netherlands)

    Berkmortel, F. van den; Gidding, C.E.M.; Kanter, M. De; Punt, C.J.A.

    2006-01-01

    Recurrent medulloblastoma carries a poor prognosis. Long-term survival has been obtained with high-dose chemotherapy with autologous stem cell transplantation and secondary irradiation. A 21-year-old woman with recurrent medulloblastoma after previous chemotherapy and radiotherapy is presented. The

  7. Debrided Skin as a Source of Autologous Stem Cells for Wound Repair

    Science.gov (United States)

    2011-08-01

    by, and are proprietary to, SA Biosciences ( Frederick , MD, http://www.sabiosciences.com/). Engraftment of dsASCs In Vivo Male rnu nude athymic rats...mesenchymal stem cells in multiple human organs. Cell Stem Cell 2008;3:301–313. 21 Katz AJ, Tholpady A, Tholpady SS et al. Cell surface and transcrip

  8. 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 being...... introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  9. Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer

    Science.gov (United States)

    Sun, Chenglin

    2017-01-01

    Mesenchymal stem cells (MSCs), an ideal cell source for regenerative therapy with no ethical issues, play an important role in diabetic foot ulcer (DFU). Growing evidence has demonstrated that MSCs transplantation can accelerate wound closure, ameliorate clinical parameters, and avoid amputation. In this review, we clarify the mechanism of preclinical studies, as well as safety and efficacy of clinical trials in the treatment of DFU. Bone marrow-derived mesenchymal stem cells (BM-MSCs), compared with MSCs derived from other tissues, may be a suitable cell type that can provide easy, effective, and cost-efficient transplantation to treat DFU and protect patients from amputation. PMID:28386568

  10. Nanoscale Mechanical Stimulation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    H Nikukar

    2014-05-01

    We observed significant responses after 1 and 2-week stimulations in cell number, cell shapes and phenotypical markers. Microarray was performed for all groups. Cell count showed normal cell growth with stimulation. However, cell surface area, cell perimeter, and arboration after 1-week stimulation showed significant increases. Immunofluorescent studies have showed significant increase in osteocalcin production after stimulation. Conclusions: Nanoscale mechanical vibration showed significant changes in human mesenchymal stem cell behaviours. Cell morphology changed to become more polygonal and increased expression of the osteoblast markers were noted. These findings with gene regulation changes suggesting nanoscale mechanostimulation has stimulated osteoblastogenesis.  Keywords:  Mesenchymal, Nanoscale, Stem Cells.

  11. Adipose-derived Mesenchymal Stem Cells and Their Reparative Potential in Ischemic Heart Disease.

    Science.gov (United States)

    Badimon, Lina; Oñate, Blanca; Vilahur, Gemma

    2015-07-01

    Adipose tissue has long been considered an energy storage and endocrine organ; however, in recent decades, this tissue has also been considered an abundant source of mesenchymal cells. Adipose-derived stem cells are easily obtained, show a strong capacity for ex vivo expansion and differentiation to other cell types, release a large variety of angiogenic factors, and have immunomodulatory properties. Thus, adipose tissue is currently the focus of considerable interest in the field of regenerative medicine. In the context of coronary heart disease, numerous experimental studies have supported the safety and efficacy of adipose-derived stem cells in the setting of myocardial infarction. These results have encouraged the clinical use of these stem cells, possibly prematurely. Indeed, the presence of cardiovascular risk factors, such as hypertension, coronary disease, diabetes mellitus, and obesity, alter and reduce the functionality of adipose-derived stem cells, putting in doubt the efficacy of their autologous implantation. In the present article, white adipose tissue is described, the stem cells found in this tissue are characterized, and the use of these cells is discussed according to the preclinical and clinical trials performed so far.

  12. Adult human nasal mesenchymal-like stem cells restore cochlear spiral ganglion neurons after experimental lesion.

    Science.gov (United States)

    Bas, Esperanza; Van De Water, Thomas R; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M; Goldstein, Bradley J

    2014-03-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic.

  13. Derivation of multipotent mesenchymal precursors from human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    2005-06-01

    Full Text Available BACKGROUND: Human embryonic stem cells provide access to the earliest stages of human development and may serve as a source of specialized cells for regenerative medicine. Thus, it becomes crucial to develop protocols for the directed differentiation of embryonic stem cells into tissue-restricted precursors. METHODS AND FINDINGS: Here, we present culture conditions for the derivation of unlimited numbers of pure mesenchymal precursors from human embryonic stem cells and demonstrate multilineage differentiation into fat, cartilage, bone, and skeletal muscle cells. CONCLUSION: Our findings will help to elucidate the mechanism of mesoderm specification during embryonic stem cell differentiation and provide a platform to efficiently generate specialized human mesenchymal cell types for future clinical applications.

  14. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    Science.gov (United States)

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL).

  15. Bone regeneration with osteogenically enhanced mesenchymal stem cells and their extracellular matrix proteins.

    Science.gov (United States)

    Clough, Bret H; McCarley, Matthew R; Krause, Ulf; Zeitouni, Suzanne; Froese, Jeremiah J; McNeill, Eoin P; Chaput, Christopher D; Sampson, H Wayne; Gregory, Carl A

    2015-01-01

    Although bone has remarkable regenerative capacity, about 10% of long bone fractures and 25% to 40% of vertebral fusion procedures fail to heal. In such instances, a scaffold is employed to bridge the lesion and accommodate osteoprogenitors. Although synthetic bone scaffolds mimic some of the characteristics of bone matrix, their effectiveness can vary because of biological incompatibility. Herein, we demonstrate that a composite prepared with osteogenically enhanced mesenchymal stem cells (OEhMSCs) and their extracellular matrix (ECM) has an unprecedented capacity for the repair of critical-sized defects of murine femora. Furthermore, OEhMSCs do not cause lymphocyte activation, and ECM/OEhMSC composites retain their in vivo efficacy after cryopreservation. Finally, we show that attachment to the ECM by OEhMSCs stimulates the production of osteogenic and angiogenic factors. These data demonstrate that composites of OEhMSCs and their ECM could be utilized in the place of autologous bone graft for complex orthopedic reconstructions.

  16. Flow perfusion culture of human mesenchymal stem cells on coralline hydroxyapatite scaffolds with various pore sizes

    DEFF Research Database (Denmark)

    Bjerre, Lea; Bünger, Cody; Baatrup, Anette;

    2011-01-01

    of this study was to obtain a clinically relevant substitute size using a direct perfusion culture system. Human bone marrowderived mesenchymal stem cells were seeded on coralline hydroxyapatite scaffolds with 200 μm or 500 μm pores, and resulting constructs were cultured in a perfusion bioreactor or in static......Bone grafts are widely used in orthopaedic reconstructive surgery, but harvesting of autologous grafts is limited due to donor site complications. Bone tissue engineering is a possible alternative source for substitutes, and to date, mainly small scaffold sizes have been evaluated. The aim...... culture for up to 21 days and analysed for cell distribution and osteogenic differentiation using histological stainings, alkaline phosphatase activity assay, and real-time RT-PCR on bone markers. We found that the number of cells was higher during static culture at most time points and that the final...

  17. Autologous tissue patch rich in stem cells created in the subcutaneous tissue

    Institute of Scientific and Technical Information of China (English)

    Ignacio; Garcia-Gomez; Krishnamurthy; P; Gudehithlu; Jose; A; L; Arruda; Ashok; K; Singh

    2015-01-01

    AIM:To investigate whether we could create natural autologous tissue patches in the subcutaneous space for organ repair. METHODS: We implanted the following three types of inert foreign bodies in the subcutaneous tissue of rats to produce autologous tissue patches of different geometries:(1) a large-sized polyvinyl tube(L = 25 mm,internal diameter = 7 mm) sealed at both ends by heat application for obtaining a large flat piece of tissue patch for organ repair;(2) a fine polyvinyl tubing(L = 25 mm,internal diameter = 3 mm) for creating cylindrically shaped grafts for vascular or nerve repair; and(3) a slurry of polydextran particle gel for inducing a bladder-like tissue. Implantation of inert materials was carried out by making a small incision on one or either side of the thoracic-lumbar region of rats. Subcutaneous pockets were created by blunt dissection around the incision into which the inert bodies were inserted(1 or 2 per rat). The incisions were closed with silk sutures,and the animals were allowed to recover. In case of the polydextran gel slurry 5 m L of the slurry was injected in the subcutaneous space using an 18 gauge needle. After implanting the foreign bodies a newly regenerated encapsulating tissue developed around the foreign bodies. The tissues were harvested after 4-42 d of implantation and studied by gross examination,histology,and histochemistry for organization,vascularity,and presence of mesenchymal stem cells(MSCs)(CD271+CD34+ cells). RESULTS: Implanting a large cylindrically shaped polyvinyl tube resulted in a large flat sheet of tissue that could be tailored to a specific size and shape for use as a tissue patch for repairing large organs. Implanting a smaller sized polyvinyl tube yielded a cylindrical tissue that could be useful for repairing nerves and blood vessels. This type of patch could be obtained in different lengths by varying the length of the implanted tube. Implanting a suspension of inert polydextran suspension gave rise to a

  18. Caspases and p38 MAPK regulate endothelial cell adhesiveness for mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Irina A Potapova

    Full Text Available Mesenchymal stem cells natively circulating or delivered into the blood stream home to sites of injury. The mechanism of mesenchymal stem cell homing to sites of injury is poorly understood. We have shown that the development of apoptosis in endothelial cells stimulates endothelial cell adhesiveness for mesenchymal stem cells. Adhesion of mesenchymal stem cells to apoptotic endothelial cells depends on the activation of endothelial caspases and p38 MAPK. Activation of p38 MAPK in endothelial cells has a primary effect while the activation of caspases potentiates the mesenchymal stem cell adhesion. Overall, our study of the mesenchymal stem cell interaction with endothelial cells indicates that mesenchymal stem cells recognize and specifically adhere to distressed/apoptotic endothelial cells.

  19. 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 ...

  20. Mesenchymal Stem Cell Transplantation Attenuates Brain Injury After Neonatal Stroke

    NARCIS (Netherlands)

    van Velthoven, Cindy T. J.; Sheldon, R. Ann; Kavelaars, Annemieke; Derugin, Nikita; Vexler, Zinaida S.; Willemen, Hanneke L. D. M.; Maas, Mirjam; Heijnen, Cobi J.; Ferriero, Donna M.

    2013-01-01

    Background and Purpose-Brain injury caused by stroke is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. Mesenchymal stem cells (MSC) have been shown to improve outcome after neonatal hypoxic-ischemic brain injury mainly by secretion of growth factors stimulati

  1. 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.

  2. Transition of mesenchymal stem/stromal cells to endothelial cells

    NARCIS (Netherlands)

    M. Crisan (Mihaela)

    2013-01-01

    textabstractMesenchymal stem/stromal cells (MSCs) are heterogeneous. A fraction of these cells constitute multipotent cells that can self-renew and mainly give rise to mesodermal lineage cells such as adipocytes, osteocytes and chondrocytes. The ability of MSCs to differentiate into endothelial cell

  3. Effects of EdU labeling on mesenchymal stem cells

    OpenAIRE

    Ning, Hongxiu; Albersen, Maarten; Lin, Guiting; Lue, Tom F.; Lin, Ching-Shwun

    2013-01-01

    Thymidine analog 5-ethynyl-2-deoxyuridine (EdU) has recently been used for tracking mesenchymal stem cells (MSCs). In the present study, we tested whether EdU was cytotoxic and whether it interfered with differentiation, cytokine secretion and migration of MSCs.

  4. Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival

    DEFF Research Database (Denmark)

    Kølle, Stig-Frederik Trojahn; Fischer-Nielsen, Anne; Mathiasen, Anders Bruun

    2013-01-01

    Autologous fat grafting is increasingly used in reconstructive surgery. However, resorption rates ranging from 25% to 80% have been reported. Therefore, methods to increase graft viability are needed. Here, we report the results of a triple-blind, placebo-controlled trial to compare the survival...... of fat grafts enriched with autologous adipose-derived stem cells (ASCs) versus non-enriched fat grafts....

  5. Skin-derived mesenchymal stem cells%皮肤间质干细胞

    Institute of Scientific and Technical Information of China (English)

    杨涛; 程波

    2011-01-01

    皮肤干细胞的研究长期限定在表皮和毛囊隆突区,皮肤间质来源的干细胞和造血干细胞同样具有分化成脂肪细胞、平滑肌细胞、骨细胞、软骨细胞,甚至神经元和神经胶质细胞的潜能.毛囊周围结缔组织鞘、毛乳头和毛囊间真皮都可能含有多潜能干细胞,未来可能作为自体移植细胞治疗的潜在供体.主要概述皮肤问质干细胞的定位、表面标记、功能和潜在的临床应用价值.%For a long time,skin stem cell research has been focused on the epidermis and hair follicle bulge.It has been demonstrated that stem cells and hematopoietic stem cells from the mesenchymal compartments of the skin have the potential to differentiate into adipocytes,smooth muscle cells,osteocytes,chondrocytes,and even neurons and glia.The perifollicular connective tissue sheath,papilla and interfollicular dermis crystallize as the likely anatomic niche for these multipotent dermal cells; hence,they have the potential to function as an easily accessible,autologous source for stem cell transplantation.This article describes the location,surface antigens,function and potential applications of skin-derived mesenchymal stem cells.

  6. Clinical study of autologous bone marrow mesenchymal stem cells transplantation through proper hepatic artery for decompensated cirrhosis patients%经肝固有动脉自体骨髓间充质干细胞移植治疗失代偿期肝硬化的疗效及安全性

    Institute of Scientific and Technical Information of China (English)

    郑盛; 杨涓; 刘琼; 楼维新

    2016-01-01

    。随访至第48周,移植组与对照组病死率及肝癌发生率均差异无统计学意义(χ2=4.815、6.286,P 均>0.05)。全部患者在移植术中,移植术后近期未发生严重并发症。结论经肝固有动脉自体 BMSC 移植治疗失代偿期肝硬化是一种安全、有效的方法,可作为肝移植治疗的过渡或补充治疗。%Objective To investigate the clinical therapeutic effect and safety of autologous bone marrow mesenchymal stem cells (BMSC)transplantation through proper hepatic artery in patients with decompensated liver cirrhosis.Methods 4,12,24,48,there were significant improvements in ALT,Alb,TBiL,PT and MELD (F =6.172,9.795,10.961 , 11 .198,19.652,P =0.000,respectively)than those at baseline.In control group,some parameters,including ALT,Alb and TBiL,had significant improvement (F =5.594,13.664,12.612,P =0.000,respectively),while other parameters, including PT and MELD,did not changed before and after therapy.At week 48,ALT,Alb,TBiL,PT and MELD showed significant differences between transplantation and control groups (t =5.477,8.830,6.371 ,11 .362,9.426,P <0.05, respectively).No significant differences were observed in incidence of HCC and mortality (χ2 =4.815、6.286,P <0.05, respectively).Additionally,no severe adverse effects occured in patients during and after transplantation.Conclusion Autologous BMSC transplantation through proper hepatic artery for decompensated liver cirrhosis is a safe and effective therapy,which could be a bridging or a complementary treatment.

  7. Mesenchymal Stem Cells: Rising Concerns over Their Application in Treatment of Type One Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Seyed Jafar Hashemian

    2015-01-01

    Full Text Available Type 1 diabetes mellitus (T1DM is an autoimmune disorder that leads to beta cell destruction and lowered insulin production. In recent years, stem cell therapies have opened up new horizons to treatment of diabetes mellitus. Among all kinds of stem cells, mesenchymal stem cells (MSCs have been shown to be an interesting therapeutic option based on their immunomodulatory properties and differentiation potentials confirmed in various experimental and clinical trial studies. In this review, we discuss MSCs differential potentials in differentiation into insulin-producing cells (IPCs from various sources and also have an overview on currently understood mechanisms through which MSCs exhibit their immunomodulatory effects. Other important issues that are provided in this review, due to their importance in the field of cell therapy, are genetic manipulations (as a new biotechnological method, routes of transplantation, combination of MSCs with other cell types, frequency of transplantation, and special considerations regarding diabetic patients’ autologous MSCs transplantation. At the end, utilization of biomaterials either as encapsulation tools or as scaffolds to prevent immune rejection, preparation of tridimensional vascularized microenvironment, and completed or ongoing clinical trials using MSCs are discussed. Despite all unresolved concerns about clinical applications of MSCs, this group of stem cells still remains a promising therapeutic modality for treatment of diabetes.

  8. Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Webster Keith A

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSC are pluripotent cells, present in the bone marrow and other tissues that can differentiate into cells of all germ layers and may be involved in tissue maintenance and repair in adult organisms. Because of their plasticity and accessibility these cells are also prime candidates for regenerative medicine. The contribution of stem cell aging to organismal aging is under debate and one theory is that reparative processes deteriorate as a consequence of stem cell aging and/or decrease in number. Age has been linked with changes in osteogenic and adipogenic potential of MSCs. Results Here we report on changes in global gene expression of cultured MSCs isolated from the bone marrow of mice at ages 2, 8, and 26-months. Microarray analyses revealed significant changes in the expression of more than 8000 genes with stage-specific changes of multiple differentiation, cell cycle and growth factor genes. Key markers of adipogenesis including lipoprotein lipase, FABP4, and Itm2a displayed age-dependent declines. Expression of the master cell cycle regulators p53 and p21 and growth factors HGF and VEGF also declined significantly at 26 months. These changes were evident despite multiple cell divisions in vitro after bone marrow isolation. Conclusions The results suggest that MSCs are subject to molecular genetic changes during aging that are conserved during passage in culture. These changes may affect the physiological functions and the potential of autologous MSCs for stem cell therapy.

  9. Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: A pilot study

    Directory of Open Access Journals (Sweden)

    Sudesh Prabhakar

    2012-01-01

    Full Text Available Background: Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder with no effective treatment. Stem cell therapy may be one of the promising treatment options for such patients. Aim: To assess the feasibility, efficacy and safety of autologous bone marrow-derived stem cells in patients of ALS. Settings and Design: We conducted an open-label pilot study of autologous bone marrow-derived stem cells in patients with ALS attending the Neurology Clinic of a tertiary care referral centre. Materials and Methods: Ten patients with ALS with mean revised ALS Functional Rating Scale (ALSFRS-R score of 30.2 (± 10.58 at baseline received intrathecal autologous bone marrow-derived stem cells. Primary end point was improvement in the ALSFRS-R score at 90, 180, 270 and 365 days post therapy. Secondary endpoints included ALSFRS-R subscores, time to 4-point deterioration, median survival and reported adverse events. Paired t-test was used to compare changes in ALSFRS-R from baseline and Kaplan-Meier analysis was used for survival calculations. Results: There was no significant deterioration in ALSFRS-R composite score from baseline at one-year follow-up (P=0.090. The median survival post procedure was 18.0 months and median time to 4-point deterioration was 16.7 months. No significant adverse events were reported. Conclusion: Autologous bone marrow-derived stem cell therapy is safe and feasible in patients of ALS. Short-term follow-up of ALSFRS-R scores suggests a trend towards stabilization of disease. However, the benefit needs to be confirmed in the long-term follow-up period.

  10. Glial origin of mesenchymal stem cells in a tooth model system

    NARCIS (Netherlands)

    Kaukua, Nina; Shahidi, Maryam Khatibi; Konstantinidou, Chrysoula; Dyachuk, Vyacheslav; Kaucka, Marketa; Furlan, Alessandro; An, Zhengwen; Wang, Longlong; Hultman, Isabell; Ahrlund-Richter, Lars; Blom, Hans; Brismar, Hjalmar; Lopes, Natalia Assaife; Pachnis, Vassilis; Suter, Ueli; Clevers, Hans; Thesleff, Irma; Sharpe, Paul; Ernfors, Patrik; Fried, Kaj; Adameyko, Igor

    2014-01-01

    Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells fo

  11. Analysis of the efficacy and prognosis on first-line autologous hematopoietic stem cell transplantation of patients with multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    邹徳慧

    2013-01-01

    Objective To explore the efficacy and prognosis of first-line autologous hematopoietic stem cell transplantation(ASCT) for newly diagnosed patients with multiple myeloma(MM).Methods From January 2005 to

  12. Specific Factors Influence the Success of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Thissiane L. Gonçalves

    2009-01-01

    Full Text Available Successful hematopoietic stem cell transplantation (HSCT, both autologous and allogeneic, requires a rapid and durable engraftment, with neutrophil (>500/µL and platelet (>20,000/µL reconstitution. Factors influencing engraftment after autologous or allogeneic HSCT were investigated in 65 patients: 25 autologous peripheral stem cell transplantation (PBSCT and 40 allogeneic bone marrow transplantation (BMT patients. The major factor affecting engraftment was the graft source for HSCT. Neutrophil and platelet recovery were more rapid in autologous PBSCT than in allogeneic BMT [neutrophil occurring in median on day 10.00 (09.00/11.00 and 19.00 (16.00/23.00 and platelet on day 11.00 (10.00/13.00 and 21.00 (18.00/25.00, respectively; p < 0.0001]. The type of disease also affected engraftment, where multiple myeloma (MM and lymphoma showed faster engraftment when compared with leukemia, syndrome myelodysplastic (SMD and aplastic anemia (AA and MM presented the best overall survival (OS in a period of 12 months. Other factors included the drug used in the conditioning regimen (CR, where CBV, melphalan (M-200 and FluCy showed faster engraftment and M-200 presented the best OS, in a period of 12 months and age, where 50–59 years demonstrated faster engraftment. Sex did not influence neutrophil and platelet recovery.

  13. Labeling of mesenchymal stem cells by bioconjugated quantum dots.

    Science.gov (United States)

    Shah, Bhranti S; Clark, Paul A; Moioli, Eduardo K; Stroscio, Michael A; Mao, Jeremy J

    2007-10-01

    Long-term labeling of stem cells during self-replication and differentiation benefits investigations of development and tissue regeneration. We report the labeling of human mesenchymal stem cells (hMSCs) with RGD-conjugated quantum dots (QDs) during self-replication, and multilineage differentiations into osteogenic, chondrogenic, and adipogenic cells. QD-labeled hMSCs remained viable as unlabeled hMSCs from the same subpopulation. These findings suggest the use of bioconjugated QDs as an effective probe for long-term labeling of stem cells.

  14. Mesenchymal stem cells as therapeutic delivery vehicles targeting tumor stroma

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Christensen, Rikke; Sørensen, Flemming Brandt

    2011-01-01

    The field of stem cell biology continues to evolve by characterization of further types of stem cells and by exploring their therapeutic potential for experimental and clinical applications. Human mesenchymal stem cells (hMSCs) are one of the most promising candidates simply because...... better understanding and in vivo supporting data. The homing ability of hMSCs was investigated by creating a human xenograft model by transplanting an ovarian cancer cell line into immunocompromised mice. Then, genetically engineered hMSC-telo1 cells were injected through the tail vein...

  15. 经肝固有动脉自体骨髓间充质干细胞移植治疗肝硬化失代偿期患者%Treated with autologous bone marrow mesenchymal stem cells transplantation through proper hepatic artery for patients with decompensated cirrhosis

    Institute of Scientific and Technical Information of China (English)

    郑盛; 杨涓; 刘琼; 楼维新

    2015-01-01

    Objective To investigate the clinical therapeutic effect and safety of autologous bone marrow mesenchymal stem cells ( BMSCs ) transplantation through proper hepatic artery in the treatment of patients with decompensated liver cirrhosis . Methods A total of 84 patients with decompensated liver cirrhosis in the 533 Hospital of Chinese People′s Liberation Army were randomly divided into transplantation group ( n=36 ) and control group ( n=48 ) .Patients in the control group received routine treatment and patients in the transplantation group received additional autologous BMSCs transplantation through proper hepatic artery .ALT, ALB, TBIL, PT and MELD were evaluated in both groups.Patients were followed up in 4, 12, 24, and 48 weeks after the treatment , respectively. Parameters of coagulation function index and liver function index of the two groups were evaluated with Student's t test;relevant indexes of different time in the same group after the treament were compared with single factor analysis of variance .LSD was used for pairwise comparison and Chi-square test was used to compare the occurring ratio of liver cancer and death in the two groups .Results After four weeks treatment in transplantation group , ascites subsided in 15 cases (41.7%), abdominal distention disappeared in 21 cases (58.3%) and edema of lower limbs relieved in 13 cases (36.1%), while there were 15 cases (31.3%), 20 cases (41.7%) and 11 case (22.9%) respectively in the control group.All the differences were statistically significant (χ2=8.341, 12.689,9 .837, all P<0.05). At weeks 12, 24, 48, there were significant improvements in transplantation group compared with prior treatment for ALB, TBIL, PT and MELD (F=9.795, 10.961, 11.198, 19.652, all P<0.05);there were significant improvements at weeks 4, 12, 24, 48 for ALT (F=61.72 , P<0.05).In the control group, there were significant improvements at weeks 24, 48 compared with prior treatment for ALB and TBIL (F=13.664, 12.612, all P<0

  16. [Autologous stem cell transplantation for autoimmune diseases: recommendations from the SFGM-TC].

    Science.gov (United States)

    Farge, D; Terriou, L; Badoglio, M; Cras, A; Desreumaux, P; Hadj-Khelifa, S; Marjanovic, Z; Moisan, A; Dulery, R; Faucher, C; Hij, A; Martin, T; Vermersch, P; Yakoub-Agha, I

    2014-08-01

    Autologous hematopoietic stem cell transplantation is a valid alternative to immunosuppressive treatment in patients with auto-immune disease; however, the role of this approach remains subject to debate. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. In this article we give an overview regarding the indications of autologous stem cell transplantation in auto-immune diseases as well as recommendations regarding post-transplant follow-up of patients.

  17. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

    Directory of Open Access Journals (Sweden)

    Patrizia Tosi

    2012-11-01

    Full Text Available Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

  18. [Monomorphic post-transplant T-lymphoproliferative disorder after autologous stem cell transplantation for multiple myeloma].

    Science.gov (United States)

    Ishikawa, Tetsuya; Shimizu, Hiroaki; Takei, Toshifumi; Koya, Hiroko; Iriuchishima, Hirono; Hosiho, Takumi; Hirato, Junko; Kojima, Masaru; Handa, Hiroshi; Nojima, Yoshihisa; Murakami, Hirokazu

    2016-01-01

    We report a rare case of T cell type monomorphic post-transplant lymphoproliferative disorders (PTLD) after autologous stem cell transplantation. A 53-year-old man with multiple myeloma received autologous stem cell transplantation and achieved a very good partial response. Nine months later, he developed a high fever and consciousness disturbance, and had multiple swollen lymph nodes and a high titer of Epstein-Barr (EB) virus DNA in his peripheral blood. Neither CT nor MRI of the brain revealed any abnormalities. Cerebrospinal fluid contained no malignant cells, but the EB virus DNA titer was high. Lymph node biopsy revealed T cell type monomorphic PTLD. Soon after high-dose treatment with methotrexate and cytosine arabinoside, the high fever and consciousness disturbance subsided, and the lymph node swelling and EB virus DNA disappeared. Given the efficacy of chemotherapy in this case, we concluded that the consciousness disturbance had been induced by central nervous system involvement of monomorphic PTLD.

  19. Autologous Stem Cell Transplantation in Patients with Acute Myeloid Leukemia: a Single-Centre Experience

    Directory of Open Access Journals (Sweden)

    Kakucs Enikő

    2013-04-01

    Full Text Available Introduction: Autologous haemopoietic stem cell transplantation (SCT is an important treatment modality for patients with acute myeloid leukemia with low and intermediate risk disease. It has served advantages over allogenic transplantation, because it does not need a matched donor, there is no graft versus host disease, there are less complications and a faster immune reconstitution than in the allo-setting. The disadvantage is the lack of the graft versus leukaemia effect.

  20. Cytomegalovirus Reactivation in Adult Recipients of Autologous Stem Cell Transplantation: a Single Center Experience

    OpenAIRE

    Al-Rawi, Omar; Abdel-Rahman, Fawzi; Al-Najjar, Rula; Abu-Jazar, Husam; Salam, Mourad; Saad, Mustafa

    2015-01-01

    Introduction Cytomegalovirus (CMV) reactivation and infection are well-recognized complications after allogeneic stem cell transplantation (SCT). Only a few studies have addressed CMV reactivation after autologous SCT (ASCT). Methods We retrospectively reviewed medical records of 210 adult patients who underwent ASCT for lymphoma or multiple myeloma (MM) at a single center from January 1st, 2007 until December 31st, 2012. All patients were monitored weekly with CMV antigenemia test till day 4...

  1. The Mesenchymal Stem Cells From The Veterinary Sciences Perspective

    Directory of Open Access Journals (Sweden)

    Nancy B. Riaño G.

    2007-06-01

    Full Text Available The characteristics of a stem cell are determined by being undifferentiated, auto renewable, and because of having the capacity of generating cells for multiple cellular lineages, with the capacity to proliferate indefinitely in cultures. The origin of the stem cells can be embryonic (blastomers and cells of the internal mass of the blastocyst or somatic (pluripotential cells from adult tissues. The source of the somatic stem cells is the bone marrow, in which the hematopoietic stem cells and the mesenchymals (MSCs are found. Diverse studies in animal models have demonstrated that MSCs constitute a potential tool for the establishment of regenerative therapies in injured tissues. This article reviews the properties of the stem cells, their potentials, their advantages and limitations in several animal models.

  2. Effects of intra-articular injection of mesenchymal stem cells associated with platelet-rich plasma in a rabbit model of osteoarthritis.

    Science.gov (United States)

    Hermeto, L C; DeRossi, R; Oliveira, R J; Pesarini, J R; Antoniolli-Silva, A C M B; Jardim, P H A; Santana, A E; Deffune, E; Rinaldi, J C; Justulin, L A

    2016-09-02

    The current study aims to evaluate the macroscopic and histological effects of autologous mesenchymal stem cells (MSC) and platelet-rich plasma on knee articular cartilage regeneration in an experimental model of osteoarthritis. Twenty-four rabbits were randomly divided into four groups: control group, platelet-rich plasma group, autologous MSC undifferentiated group, and autologous MSC differentiated into chondrocyte group. Collagenase solution was used to induce osteoarthritis, and treatments were applied to each group at 6 weeks following osteoarthritis induction. After 60 days of therapy, the animals were euthanized and the articular surfaces were subjected to macroscopic and histological evaluations. The adipogenic, chondrogenic, and osteogenic differentiation potentials of MSCs were evaluated. Macroscopic and histological examinations revealed improved tissue repair in the MSC-treated groups. However, no difference was found between MSC-differentiated and undifferentiated chondrocytes. We found that MSCs derived from adipose tissue and platelet-rich plasma were associated with beneficial effects in articular cartilage regeneration during experimental osteoarthritis.

  3. 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 var......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...

  4. The graft of autologous adipose-derived stem cells in the corneal stromal after mechanic damage.

    Directory of Open Access Journals (Sweden)

    Xiao-Yun Ma

    Full Text Available This study was designed to explore the feasibility of using autologous rabbit adipose derived stem cells (rASCs as seed cells and polylactic-co-glycolic acid (PLGA as a scaffold for repairing corneal stromal defects. rASCs isolated from rabbit nape adipose tissue were expanded and seeded on a PLGA scaffold to fabricate cell-scaffold constructs. After 1 week of cultivation in vitro, the cell-scaffold complexes were transplanted into corneal stromal defects in rabbits. In vivo, the autologous rASCs-PLGA constructed corneal stroma gradually became transparent without corneal neovascularization after 12 weeks. Hematoxylin and eosin staining and transmission electron microscopy examination revealed that their histological structure and collagen fibril distribution at 24 weeks after implantation were similar to native counterparts. As to the defect treated with PLGA alone, the stromal defects remained. And scar tissue was observed in the untreated-group. The implanted autologous ASCs survived up to 24 weeks post-transplantation and differentiated into functional keratocytes, as assessed by the expression of aldehyde-3-dehydrogenase1A1 (ALDH1A1 and cornea-specific proteoglycan keratocan. Our results revealed that autologous rASCs could be one of the cell sources for corneal stromal restoration in diseased corneas or for tissue engineering of a corneal equivalent.

  5. Umbilical cord-derived stem cells (MODULATISTTM show strong immunomodulation capacity compared to adipose tissue-derived or bone marrow-derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Phuc Van Pham

    2016-06-01

    Full Text Available Introduction: Mesenchymal stem cells (MSCs show great promise in regenerative medicine. Clinical applications of MSCs have recently increased significantly, especially for immune diseases. Autologous transplantation is considered a safe therapy. However, its main disadvantages are poor stability and quality of MSCs from patient to patient, and labor-intensive and time-consuming culture procedures. Therefore, allogeneic MSC transplantation has recently emerged as a potential replacement for autologous transplantation. and ldquo;Off the shelf and rdquo; MSC products, or so-called and ldquo;stem cell drugs and rdquo;, have rapidly developed; these products have already been approved in various countries, including Canada, Korea and Japan. This study aims to evaluate a new stem cell product or and ldquo;drug and rdquo;, termed ModulatistTM, derived from umbilical cord mesenchymal stem cells (UCMSCs, which have strong immunomodulatory properties, compared to bone marrow-derived MSCs (BMMSCs or adipose tissue-derived stem cells (ADSCs. Methods: ModulatistTM was produced from MSCs derived from whole umbilical cord (UC tissue (which includes Wharton's jelly and UC, according to GMP compliant procedures. Bone marrow- and adipose tissue-derived MSCs were isolated and proliferated in standard conditions, according to GMP compliant procedures. Immunomodulation mediated by MSCs was assessed by allogenic T cell suppression and cytokine release; role of prostaglandin E2 in the immunomodulation was also evaluated. Results: The results showed that ModulatistTM exhibited stronger immunomodulation than BMMSC and ADSC in vitro. ModulatistTM strongly suppressed allogeneic T cells proliferation and decreased cytokine production, compared to BMMSCs and ADSCs. Conclusion: ModulatistTM is a strong immunomodulator and promising MSC product. It may be useful to modulate or treat autoimmune diseases. [Biomed Res Ther 2016; 3(6.000: 687-696

  6. Early Results of Autologous Cultivated Limbal Stem Cell Transplantation in Total Limbal Stem Cell Deficiency

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Javadi

    2008-12-01

    Full Text Available

    PURPOSE: To report the early results of transplantation of autologous limbal stem cells cultivated on amniotic membrane (AM in patients with total unilateral limbal stem cell deficiency (LSCD. METHODS: Four eyes of 4 patients with total unilateral LSCD confirmed with impression cytology underwent transplantation of autologous limbal stem cell cultivated on AM. At each follow up visit, a complete eye examination with special attention to recurrence or regression of vascularization, corneal opacification, and epithelial defect healing was performed. Digital imaging was performed at each follow up visit. Impression cytology was repeated in all cases after surgery. RESULTS: The patients were followed for 5-13 months. Visual acuity improved in all cases. Decrease in corneal opacification and vascularization was obvious in 3 cases with coverage of the cornea with corneal epithelium. Sectoral conjunctivalization was evident in these 3 cases, however the corneas were ready for transplantation. The procedure failed in one case with total corneal conjunctivalization. CONCLUSION: Transplantation of autologous stem cells cultivated on AM seems to be an effective way for total LSCD. More definite judgment needs longer follow up together with long-term results of corneal transplantation in these patients.

  1. Autologous hematopoietic stem cell transplantation for autoimmune disease--is it now ready for prime time?

    Science.gov (United States)

    Atkins, Harold L; Muraro, Paolo A; van Laar, Jacob M; Pavletic, Steven Z

    2012-01-01

    Current systemic therapies are rarely curative for patients with severe life-threatening forms of autoimmune disease (AID). During the past 15 years, autologous hematopoietic stem cell transplantation (HCT) has been demonstrated to cure some patients with severe AID refractory to all other available therapies, and thus AID has become an emerging indication for cell therapy. The sustained clinical effects after autologous HCT are better explained by qualitative change in the reconstituted immune repertoire rather than transient depletion of immune cells. Since 1996, more than 1300 AID patients have been registered by the European Group for Blood and Marrow Transplantation (EBMT) and almost 500 patients by the Center for International Blood and Marrow Transplant Research (CIBMTR). Autologous HCT is most commonly performed for patients with multiple sclerosis (MS) or systemic sclerosis (SSc). Systemic lupus, Crohn's disease, type I diabetes, and juvenile idiopathic arthritis are other common indications. Allogeneic transplants are still considered too toxic for use in AID, except for cases of immune cytopenia. Although biologic therapies have been effective at controlling the manifestations of the disease, they require continuous administration, thus raising questions about their increasing costs, morbidity, and mortality related to prolonged therapy. Perhaps it is a reasonable time to ask, "Is autologous HCT for severe AID now ready for prime time?" Yet, the paucity of controlled studies, the short-term toxicities, and the upcoming availability of second-generation biologic and targeted immunotherapies argues that perhaps HCT for AID should be still limited to clinical trials. In this article, we focus on the results of autologous HCT for MS and SSc because these are the two most commonly transplanted diseases. The promising data that is emerging may establish these diseases as standard indications for HCT.

  2. Biosimilar Filgrastim in Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization and Post-Transplant Hematologic Recovery.

    Science.gov (United States)

    Marchesi, Francesco; Mengarelli, Andrea

    2016-01-01

    To date, two kinds of Granulocyte Colony-Stimulating Factors (G-CSF) have been approved for autologous peripheral blood hematopoietic stem cell (PBSCs) mobilization and posttransplant hematologic recovery after high-dose chemotherapy: filgrastim (originator and biosimilar) and lenograstim. Biosimilar filgrastim has been approved on the basis of comparable efficacy and safety in clinical studies where it has been used as chemotherapy-induced febrile neutropenia prophylaxis, but no specific pre-registration studies have been published in the transplant setting. Hence, there is still general skepticism about the role of biosimilar G-CSFs in this setting of patients. This review of biochemical, pre-clinical and clinical data suggests significant comparability of biosimilar filgrastim with both originator filgrastim and lenograstim in autologous PBSCs mobilization and post-autograft hematologic recovery.

  3. The regenerative medicine in oral and maxillofacial surgery: the most important innovations in the clinical application of mesenchymal stem cells.

    Science.gov (United States)

    Tatullo, Marco; Marrelli, Massimo; Paduano, Francesco

    2015-01-01

    Regenerative medicine is an emerging field of biotechnology that combines various aspects of medicine, cell and molecular biology, materials science and bioengineering in order to regenerate, repair or replace tissues. The oral surgery and maxillofacial surgery have a role in the treatment of traumatic or degenerative diseases that lead to a tissue loss: frequently, to rehabilitate these minuses, you should use techniques that have been improved over time. Since 1990, we started with the use of growth factors and platelet concentrates in oral and maxillofacial surgery; in the following period we start to use biomaterials, as well as several type of scaffolds and autologous tissues. The frontier of regenerative medicine nowadays is represented by the mesenchymal stem cells (MSCs): overcoming the ethical problems thanks to the use of mesenchymal stem cells from adult patient, and with the increasingly sophisticated technology to support their manipulation, MSCs are undoubtedly the future of medicine regenerative and they are showing perspectives unimaginable just a few years ago. Most recent studies are aimed to tissues regeneration using MSCs taken from sites that are even more accessible and rich in stem cells: the oral cavity turned out to be an important source of MSCs with the advantage to be easily accessible to the surgeon, thus avoiding to increase the morbidity of the patient. The future is the regeneration of whole organs or biological systems consisting of many different tissues, starting from an initial stem cell line, perhaps using innovative scaffolds together with the nano-engineering of biological tissues.

  4. Bone mesenchymal stem cell sheet transplantation combined with autologous iliac bone for repair of alveolar cleft%骨髓间充质干细胞膜片复合自体髂骨移植修复牙槽嵴裂

    Institute of Scientific and Technical Information of China (English)

    沈悦; 马海英; 张彦升; 王娟; 时炳正

    2014-01-01

    BACKGROUND:Autogenous iliac bone graft for repair of alveolar cleft often cannot achieve a stable therapeutic effect, and the graft resorption rate varies with each individual that is influenced by many factors. OBJECTIVE:To observe the bone resorption after bone marrow mesenchymal stem cel sheet transplantation with autogenous iliac cancelous bone for alveolar cleft repair. METHODS:Bilateral alveolar cleft models were prepared in dogs. Using the self-control method, bone marrow mesenchymal stem cel sheet combined with autogenous iliac bone (experimental group) and autogenous iliac bone alone (control group) were respectively implanted into the bilateral alveolar clefts. Mandible CT and microCT were used to compare the bone resorption rate, bone volume fraction, trabecular thickness, trabecular separation, and bone mineral density. RESULTS AND CONCLUSION:The bone resorption rate was significantly lower in the experimental group than the control group at 3 and 6 postoperative months (P 0.05). These findings indicate that bone marrow mesenchymal stem cel sheet transplantation combined with autogenous iliac bone graft can reduce bone resorption rate and meanwhile, promote new bone formation.%背景:临床上使用自体髂骨移植方法修复牙槽嵴裂,常常不能获得稳定的治疗效果,移植骨吸收率因人而异,受到许多因素的影响。  目的:观察骨髓间充质干细胞膜片复合自体髂骨松质骨块移植修复牙槽嵴裂术后的骨吸收情况。  方法:制备实验犬双侧牙槽嵴裂模型,采用自体对照的办法,在实验犬上颌骨两侧的裂隙分别植入骨髓间充质干细胞膜片复合犬自体髂骨骨块(实验组)和单纯犬自体髂骨骨块(对照组)。通过颌骨CT及micro CT对植骨区的骨吸收率、骨体积分数、骨小梁厚度、骨小梁分离度、骨密度进行比较。  结果与结论:术后3,6个月时实验组的骨吸收率明显低于对照组,差

  5. Mesenchymal Stem Cells from Bichat's Fat Pad: In Vitro Comparison with Adipose-Derived Stem Cells from Subcutaneous Tissue.

    Science.gov (United States)

    Broccaioli, Eugenio; Niada, Stefania; Rasperini, Giulio; Ferreira, Lorena Maria; Arrigoni, Elena; Yenagi, Vijay; Brini, Anna Teresa

    2013-04-01

    Adipose-derived stem/stromal cells (ASCs) are progenitor cells used in bone tissue engineering and regenerative medicine. Since Bichat's fat pad is easily accessible for dentists and maxillo-facial surgeons, we compared the features of ASCs from Bichat's fat pad (BFP-ASCs) with human ASCs from subcutaneous adipose tissue (SC-ASCs). BFP-ASCs isolated from a small amount of tissue were characterized for their stemness and multidifferentiative ability. They showed an important clonogenic ability and the typical mesenchymal stem cell immunophenotype. Moreover, when properly induced, osteogenic and adipogenic differentiation markers, such as alkaline phosphatase activity, collagen deposition and lipid vacuoles formation, were promptly observed. Growth of both BFP-ASCs and SC-ASCs in the presence of human serum and their adhesion to natural and synthetic scaffolds were also assessed. Both types of ASCs adapted rapidly to human autologous or heterologous sera, increasing their proliferation rate compared to standard culture condition, and all the cells adhered finely to bone, periodontal ligament, collagen membrane, and polyglycol acid filaments that are present in the oral cavity or are commonly used in oral surgery. At last, we showed that amelogenin seems to be an early osteoinductive factor for BFP-ASCs, but not SC-ASCs, in vitro. We conclude that Bichat's fat pad contains BFP-ASCs with stemness features that are able to differentiate and adhere to biological supports and synthetic materials. They are also able to proliferate in the presence of human serum. For all these reasons we propose BFP-ASCs for future therapies of periodontal defects and bone regeneration.

  6. Selective purging of human multiple myeloma cells from autologous stem cell transplant grafts using oncolytic myxoma virus

    OpenAIRE

    Bartee, Eric; Chan, Winnie S.; Moreb, Jan S.; Cogle, Christopher R.; McFadden, Grant

    2012-01-01

    Autologous stem cell transplantation (ASCT) and novel therapies have improved overall survival of patients with multiple myeloma; however, most patients relapse and eventually succumb to their disease. Evidence indicates that residual cancer cells contaminate autologous grafts and may contribute to early relapses after ASCT. Here, we demonstrate that ex vivo treatment with an oncolytic poxvirus called myxoma virus results in specific elimination of human myeloma cells by inducing rapid cellul...

  7. The Impact of Epigenetics on Mesenchymal Stem Cell Biology.

    Science.gov (United States)

    Ozkul, Yusuf; Galderisi, Umberto

    2016-11-01

    Changes in epigenetic marks are known to be important regulatory factors in stem cell fate determination and differentiation. In the past years, the investigation of the epigenetic regulation of stem cell biology has largely focused on embryonic stem cells (ESCs). Contrarily, less is known about the epigenetic control of gene expression during differentiation of adult stem cells (AdSCs). Among AdSCs, mesenchymal stem cells (MSCs) are the most investigated stem cell population because of their enormous potential for therapeutic applications in regenerative medicine and tissue engineering. In this review, we analyze the main studies addressing the epigenetic changes in MSC landscape during in vitro cultivation and replicative senescence, as well as follow osteocyte, chondrocyte, and adipocyte differentiation. In these studies, histone acetylation, DNA methylation, and miRNA expression are among the most investigated phenomena. We describe also epigenetic changes that are associated with in vitro MSC trans-differentiation. Although at the at initial stage, the epigenetics of MSCs promise to have profound implications for stem cell basic and applied research. J. Cell. Physiol. 231: 2393-2401, 2016. © 2016 Wiley Periodicals, Inc.

  8. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series

    Directory of Open Access Journals (Sweden)

    Pak Jaewoo

    2011-07-01

    Full Text Available Abstract Introduction This is a series of clinical case reports demonstrating that a combination of percutaneously injected autologous adipose-tissue-derived stem cells, hyaluronic acid, platelet rich plasma and calcium chloride may be able to regenerate bones in human osteonecrosis, and with addition of a very low dose of dexamethasone, cartilage in human knee osteoarthritis. Case reports Stem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. These stem cells, along with hyaluronic acid, platelet rich plasma and calcium chloride, were injected into the right hip of a 29-year-old Korean woman and a 47-year-old Korean man. They both had a history of right hip osteonecrosis of the femoral head. For cartilage regeneration, a 70-year-old Korean woman and a 79-year-old Korean woman, both with a long history of knee pain due to osteoarthritis, were injected with stem cells along with hyaluronic acid, platelet rich plasma, calcium chloride and a nanogram dose of dexamethasone. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed. Conclusions The MRI data for all the patients in this series showed significant positive changes. Probable bone formation was clear in the patients with osteonecrosis, and cartilage regeneration in the patients with osteoarthritis. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional status all improved. Autologous mesenchymal stem cell injection, in conjunction with hyaluronic acid, platelet rich plasma and calcium chloride, is a promising minimally invasive therapy for osteonecrosis of femoral head and, with low-dose dexamethasone, for osteoarthritis of human knees.

  9. Mesenchymal stem cells and induced pluripotent stem cells as therapies for multiple sclerosis.

    Science.gov (United States)

    Xiao, Juan; Yang, Rongbing; Biswas, Sangita; Qin, Xin; Zhang, Min; Deng, Wenbin

    2015-04-24

    Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory demyelinating disorder of the central nervous system that leads to permanent neurological deficits. Current MS treatment regimens are insufficient to treat the irreversible neurological disabilities. Tremendous progress in the experimental and clinical applications of cell-based therapies has recognized stem cells as potential candidates for regenerative therapy for many neurodegenerative disorders including MS. Mesenchymal stem cells (MSC) and induced pluripotent stem cell (iPSCs) derived precursor cells can modulate the autoimmune response in the central nervous system (CNS) and promote endogenous remyelination and repair process in animal models. This review highlights studies involving the immunomodulatory and regenerative effects of mesenchymal stem cells and iPSCs derived cells in animal models, and their translation into immunomodulatory and neuroregenerative treatment strategies for MS.

  10. Mesenchymal Stem Cells and Induced Pluripotent Stem Cells as Therapies for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Juan Xiao

    2015-04-01

    Full Text Available Multiple sclerosis (MS is a chronic, autoimmune, inflammatory demyelinating disorder of the central nervous system that leads to permanent neurological deficits. Current MS treatment regimens are insufficient to treat the irreversible neurological disabilities. Tremendous progress in the experimental and clinical applications of cell-based therapies has recognized stem cells as potential candidates for regenerative therapy for many neurodegenerative disorders including MS. Mesenchymal stem cells (MSC and induced pluripotent stem cell (iPSCs derived precursor cells can modulate the autoimmune response in the central nervous system (CNS and promote endogenous remyelination and repair process in animal models. This review highlights studies involving the immunomodulatory and regenerative effects of mesenchymal stem cells and iPSCs derived cells in animal models, and their translation into immunomodulatory and neuroregenerative treatment strategies for MS.

  11. Umbilical cord as a mesenchymal stem cell source for treating joint pathologies.

    Science.gov (United States)

    Arufe, Maria Carmen; De la Fuente, Alexandre; Fuentes, Isaac; Toro, Francisco Javier De; Blanco, Francisco Javier

    2011-06-18

    Articular cartilage disorders and injuries often result in life-long chronic pain and compromised quality of life. Regrettably, the regeneration of articular cartilage is a continuing challenge for biomedical research. One of the most promising therapeutic approaches is cell-based tissue engineering, which provides a healthy population of cells to the injured site but requires differentiated chondrocytes from an uninjured site. The use of healthy chondrocytes has been found to have limitations. A promising alternative cell population is mesenchymal stem cells (MSCs), known to possess excellent proliferation potential and proven capability for differentiation into chondrocytes. The "immunosuppressive" property of human MSCs makes them an important candidate for allogeneic cell therapy. The use of allogeneic MSCs to repair large defects may prove to be an alternative to current autologous and allogeneic tissue-grafting procedures. An allogeneic cell-based approach would enable MSCs to be isolated from any donor, expanded and cryopreserved in allogeneic MSC banks, providing a readily available source of progenitors for cell replacement therapy. These possibilities have spawned the current exponential growth in stem cell research in pharmaceutical and biotechnology communities. Our objective in this review is to summarize the knowledge about MSCs from umbilical cord stroma and focus mainly on their applications for joint pathologies.

  12. Transdifferentiation of Human Hair Follicle Mesenchymal Stem Cells into Red Blood Cells by OCT4

    Directory of Open Access Journals (Sweden)

    Zhijing Liu

    2015-01-01

    Full Text Available Shortage of red blood cells (RBCs, erythrocytes can have potentially life-threatening consequences for rare or unusual blood type patients with massive blood loss resulting from various conditions. Erythrocytes have been derived from human pluripotent stem cells (PSCs, but the risk of potential tumorigenicity cannot be ignored, and a majority of these cells produced from PSCs express embryonic ε- and fetal γ-globins with little or no adult β-globin and remain nucleated. Here we report a method to generate erythrocytes from human hair follicle mesenchymal stem cells (hHFMSCs by enforcing OCT4 gene expression and cytokine stimulation. Cells generated from hHFMSCs expressed mainly the adult β-globin chain with minimum level of the fetal γ-globin chain. Furthermore, these cells also underwent multiple maturation events and formed enucleated erythrocytes with a biconcave disc shape. Gene expression analyses showed that OCT4 regulated the expression of genes associated with both pluripotency and erythroid development during hHFMSC transdifferentiation toward erythroid cells. These findings show that mature erythrocytes can be generated from adult somatic cells, which may serve as an alternative source of RBCs for potential autologous transfusion.

  13. Autologous Stem Cells Transplantation in Egyptian Patients with Liver Cirrhosis on Top of Hepatitis C Virus

    Science.gov (United States)

    Al Tayeb, Hoda; El Dorry, Ahmed; Amer, Nehad; Mowafy, Nadia; Zimaity, Maha; Bayoumy, Essam; Saleh, Shereen A.

    2015-01-01

    Background and Objectives Use of pluripotent stem cells is an ideal solution for liver insufficiencies. This work aims is to evaluate the safety and feasibility of autologous stem cells transplantation (SCT) in Egyptian patients of liver cirrhosis on top of hepatitis C virus (HCV). Subjects and Results 20 patients with HCV induced liver cirrhosis were divided into 2 groups. Group I: included 10 patients with liver cirrhosis Child score ≥9, for whom autologous stem cell transplantation was done using granulocyte colony stimulating factor (G-CSF) for stem cells mobilization. Separation and collection of the peripheral blood stem cells was done by leukapheresis. G-CSF mobilized peripheral blood mononuclear cells (G-CSF PB-MNCs) were counted by flow cytometry. Stem cell injection into the hepatic artery was done. Group II: included 10 patients with HCV induced liver cirrhosis as a control group. Follow up and comparison between both groups were done over a follow up period of 6 months. The procedure was well tolerated. Mobilization was successful and the total number of G-CSF PB-MNCs in the harvests ranged from 25×106 to 191×106. There was improvement in the quality of life, serum albumin, total bilirubin, liver enzymes and the Child-Pugh score of group I over the first two-three months after the procedure. Conclusion SCT in HCV induced liver cirrhosis is a safe procedure. It can improve the quality of life and hepatic functions transiently with no effect on the life expectancy or the fate of the liver cirrhosis. PMID:26634069

  14. Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    Cella Luigi

    2011-08-01

    Full Text Available Abstract Purpose Bisphosphonate - related osteonecrosis of the JAW (BRONJ is a well known side effect of bisphosphonate therapies in oncologic and non oncologic patients. Since to date no definitive consensus has been reached on the treatment of BRONJ, novel strategies for the prevention, risk reduction and treatment need to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to alendronate and pamidronate treatment of osteoporosis. The patient was unresponsive to recommended treatment of the disease, and her BRONJ was worsening. Since bone marrow stem cells are know as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone and other tissue, we performed autologous bone marrow stem cell transplantation into the BRONJ lesion of the patient. Methods Under local anesthesia a volume of 75 ml of bone marrow were harvested from the posterior superior iliac crest by aspiration into heparinized siringes. The cell suspension was concentrated, using Ficoll - Hypaque® centrifugation procedures, in a final volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the patient underwent surgical toilet, local anesthesia was done and spongostan was applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of stem cells suspension and 1 ml of patient's activated platelet-rich plasma were injected in the lesion of BRONJ. Results A week later the residual spongostan was removed and two weeks later resolution of symptoms was obtained. Then the lesion improved with progressive superficialization of the mucosal layer and CT scan, performed 15 months later, shows improvement also of bone via concentric ossification: so complete healing of BRONJ (stage 0 was obtained in our patient, and 30 months later the patient is well and without signs of BRONJ. Conclusion To our knowledge this is the first case of BRONJ successfully treated with

  15. Recent Advances in Hydroxyapatite Scaffolds Containing Mesenchymal Stem Cells.

    Science.gov (United States)

    Michel, John; Penna, Matthew; Kochen, Juan; Cheung, Herman

    2015-01-01

    Modern day tissue engineering and cellular therapies have gravitated toward using stem cells with scaffolds as a dynamic modality to aid in differentiation and tissue regeneration. Mesenchymal stem cells (MSCs) are one of the most studied stem cells used in combination with scaffolds. These cells differentiate along the osteogenic lineage when seeded on hydroxyapatite containing scaffolds and can be used as a therapeutic option to regenerate various tissues. In recent years, the combination of hydroxyapatite and natural or synthetic polymers has been studied extensively. Due to the interest in these scaffolds, this review will cover the wide range of hydroxyapatite containing scaffolds used with MSCs for in vitro and in vivo experiments. Further, in order to maintain a progressive scope of the field this review article will only focus on literature utilizing adult human derived MSCs (hMSCs) published in the last three years.

  16. Recent Advances in Hydroxyapatite Scaffolds Containing Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    John Michel

    2015-01-01

    Full Text Available Modern day tissue engineering and cellular therapies have gravitated toward using stem cells with scaffolds as a dynamic modality to aid in differentiation and tissue regeneration. Mesenchymal stem cells (MSCs are one of the most studied stem cells used in combination with scaffolds. These cells differentiate along the osteogenic lineage when seeded on hydroxyapatite containing scaffolds and can be used as a therapeutic option to regenerate various tissues. In recent years, the combination of hydroxyapatite and natural or synthetic polymers has been studied extensively. Due to the interest in these scaffolds, this review will cover the wide range of hydroxyapatite containing scaffolds used with MSCs for in vitro and in vivo experiments. Further, in order to maintain a progressive scope of the field this review article will only focus on literature utilizing adult human derived MSCs (hMSCs published in the last three years.

  17. 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.

  18. Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

    Science.gov (United States)

    Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

    2015-01-01

    Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies.

  19. Derivation of Stromal (Skeletal, Mesenchymal) Stem-like cells from Human Embryonic Stem Cells

    DEFF Research Database (Denmark)

    Mahmood, Amer; Harkness, Linda; Abdallah, Basem

    2012-01-01

    stromal (mesenchymal, skeletal) stem cell (hMSC)-like population, known to be osteoblastic cell precursors and to test their osteoblastic differentiation capacity in ex vivo cultures and in vivo. We cultured hESC in a feeder-free environment using serum replacement and as suspension aggregates (embryoid...

  20. A question of ethics: selling autologous stem cell therapies flaunts professional standards.

    Science.gov (United States)

    Munsie, Megan; Hyun, Insoo

    2014-11-01

    The idea that the body's own stem cells could act as a repair kit for many conditions, including cardiac repair, underpins regenerative medicine. While progress is being made, with hundreds of clinical trials underway to evaluate possible autologous cell-based therapies, some patients and physicians are not prepared to wait and are pursuing treatments without evidence that the proposed treatments are effective, or even safe. This article explores the inherent tension between patients, practitioners and the need to regulate the development and commercialization of new cellular therapies--even when the cells come from the patient.

  1. Neck Rhabdoid Tumors: Clinical Features and Consideration of Autologous Stem Cell Transplant.

    Science.gov (United States)

    Wolfe, Adam D; Capitini, Christian M; Salamat, Shahriar M; DeSantes, Kenneth; Bradley, Kristin A; Kennedy, Tabassum; Dehner, Louis P; Patel, Neha J

    2017-04-03

    Extrarenal malignant rhabdoid tumors (MRT) have a poor prognosis despite aggressive therapy. Adding high-dose chemotherapy with autologous stem cell rescue (HDC-ASCR) as consolidative therapy for MRT is controversial. We describe 2 patients, age 13 years and 19 months, with unresectable neck MRT. After chemotherapy and radiotherapy, both underwent HDC-ASCR and remain in remission over 4 years later. We reviewed all published cases of neck MRT, and found poorer outcomes and more variable age of presentation and time to progression than MRT at other sites. Neck MRT may represent a higher-risk subset of MRT, and addition of HDC-ASCR merits consideration.

  2. Differentiation of human mesenchymal stem cell spheroids under microgravity conditions

    Directory of Open Access Journals (Sweden)

    Cerwinka Wolfgang H

    2012-06-01

    Full Text Available Abstract To develop and characterize a novel cell culture method for the generation of undifferentiated and differentiated human mesenchymal stem cell 3D structures, we utilized the RWV system with a gelatin-based scaffold. 3 × 106 cells generated homogeneous spheroids and maximum spheroid loading was accomplished after 3 days of culture. Spheroids cultured in undifferentiated spheroids of 3 and 10 days retained expression of CD44, without expression of differentiation markers. Spheroids cultured in adipogenic and osteogenic differentiation media exhibited oil red O staining and von Kossa staining, respectively. Further characterization of osteogenic lineage, showed that 10 day spheroids exhibited stronger calcification than any other experimental group corresponding with significant expression of vitamin D receptor, alkaline phosphatase, and ERp60 . In conclusion this study describes a novel RWV culture method that allowed efficacious engineering of undifferentiated human mesenchymal stem cell spheroids and rapid osteogenic differentiation. The use of gelatin scaffolds holds promise to design implantable stem cell tissue of various sizes and shapes for future regenerative treatment.

  3. Molecular and environmental cues in cardiac differentiation of mesenchymal stem cells

    NARCIS (Netherlands)

    Ramkisoensing, Arti Anushka

    2014-01-01

    In this thesis molecular and environmental cues in cardiac differentiation of mesenchymal stem cells were investigated. The main conclusions were that the cardiac differentiation potential of human mesenchymal stem cells negatively correlates with donor age. This in its own shows a negative relation

  4. Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

    Zhi Li; Wei Zhao; Wei Liu; Ye Zhou; Jingqiao Jia; Lifeng Yang

    2014-01-01

    Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the ifeld of nerve damage repair. In the present study, human placenta-derived mesenchymal stem cells were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the resto-ration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury.

  5. File list: NoD.Oth.05.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

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  9. MET: roles in epithelial-mesenchymal transition and cancer stemness

    Science.gov (United States)

    Jeon, Hye-Min

    2017-01-01

    In a number of cancers, deregulated MET pathway leads to aberrantly activated proliferative and invasive signaling programs that promote malignant transformation, cell motility and migration, angiogenesis, survival in hypoxia, and invasion. A better understanding of oncogenic MET signaling will help us to discover effective therapeutic approaches and to identify which tumors are likely to respond to MET-targeted cancer therapy. In this review, we will summarize the roles of MET signaling in cancer, with particular focus on epithelial-mesenchymal transition (EMT) and cancer stemness. Then, we will provide update on MET targeting agents and discuss the challenges that should be overcome for the development of an effective therapy. PMID:28164090

  10. Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

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    Feng Yan

    2015-01-01

    Full Text Available In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold in vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hitosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the ischemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial fibrillary acidic protein and a low level of expression of neuron-specific enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These findings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold has a neuroprotective effect following ischemic stroke.

  11. Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Feng Yan; Wei Yue; Yue-lin Zhang; Guo-chao Mao; Ke Gao; Zhen-xing Zuo; Ya-jing Zhang; Hui Lu

    2015-01-01

    In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffoldin vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hi-tosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the ischemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial ifbrillary acidic protein and a low level of expression of neuron-spe-ciifc enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These ifndings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chi-tosan-collagen scaffold has a neuroprotective effect following ischemic stroke.

  12. Embryonic stem cells conditioned medium enhances Wharton’s jelly-derived mesenchymal stem cells expansion under hypoxic condition

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    Prasajak, Patcharee; Rattananinsruang, Piyaporn; Chotinantakul, Kamonnaree; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat

    2014-01-01

    Mesenchymal stem cells (MSCs) are accepted as a promising tool for therapeutic purposes. However, low proliferation and early senescence are still main obstacles of MSCs expansion for using as cell-based therapy. Thus, clinical scale of cell expansion is needed to obtain a large number of cells serving for further applications. In this study, we investigated the value of embryonic stem cells conditioned medium (ESCM) for in vitro expansion of Wharton’s jelly-derived mesenchymal stem cells (WJ...

  13. Intra-arterial delivery of mesenchymal stem cells

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    Mitsuyoshi Watanabe

    2016-01-01

    Full Text Available While treatments have been developed to combat stroke, such as intravenous recombinant tissue plasminogen activator and endovascular recanalization therapies, their ability to decrease the long-term disability that accompanies stroke is limited. Currently, stem cell research focused on mesenchymal stem cells (MSCs. MSCs are multipotent, nonhematopoietic stem cells found in the stromal fraction of the bone marrow, along with the connective tissue of most organs. MSCs are an increasingly appealing cell source due to the relative ease in which they can be retrieved, developed, and handled in vitro. Despite the fact that numerous paths of stem cell transport to the brain in acute ischemic stroke (AIS exist, the intra-arterial (IA route of stem cell transport is most attractive. This is due to its great potential for clinical translation, especially considering the growing clinical application of endovascular treatment for AIS. Here, we evaluate research examining IA delivery of MSCs to the stroke region. The results of the study revealed the maximum tolerated dose and that the optimal time for administration was 24 h, following cerebral ischemia. It is important that future translational studies are performed to establish IA administration of MSCs as a widely used treatment for AIS.

  14. Composition of Mineral Produced by Dental Mesenchymal Stem Cells.

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    Volponi, A A; Gentleman, E; Fatscher, R; Pang, Y W Y; Gentleman, M M; Sharpe, P T

    2015-11-01

    Mesenchymal stem cells isolated from different dental tissues have been described to have osteogenic/odontogenic-like differentiation capacity, but little attention has been paid to the biochemical composition of the material that each produces. Here, we used Raman spectroscopy to analyze the mineralized materials produced in vitro by different dental cell populations, and we compared them with the biochemical composition of native dental tissues. We show that different dental stem cell populations produce materials that differ in their mineral and matrix composition and that these differ from those of native dental tissues. In vitro, BCMP (bone chip mass population), SCAP (stem cells from apical papilla), and SHED (stem cells from human-exfoliated deciduous teeth) cells produce a more highly mineralized matrix when compared with that produced by PDL (periodontal ligament), DPA (dental pulp adult), and GF (gingival fibroblast) cells. Principal component analyses of Raman spectra further demonstrated that the crystallinity and carbonate substitution environments in the material produced by each cell type varied, with DPA cells, for example, producing a more carbonate-substituted mineral and with SCAP, SHED, and GF cells creating a less crystalline material when compared with other dental stem cells and native tissues. These variations in mineral composition reveal intrinsic differences in the various cell populations, which may in turn affect their specific clinical applications.

  15. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

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    Patrizia Tosi

    2012-01-01

    Full Text Available

    Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

  16. Energy Metabolism in Mesenchymal Stem Cells During Osteogenic Differentiation

    Science.gov (United States)

    Shum, Laura C.; White, Noelle S.; Mills, Bradley N.; de Mesy Bentley, Karen L.

    2016-01-01

    There is emerging interest in stem cell energy metabolism and its effect on differentiation. Bioenergetic changes in differentiating bone marrow mesenchymal stem cells (MSCs) are poorly understood and were the focus of our study. Using bioenergetic profiling and transcriptomics, we have established that MSCs activate the mitochondrial process of oxidative phosphorylation (OxPhos) during osteogenic differentiation, but they maintain levels of glycolysis similar to undifferentiated cells. Consistent with their glycolytic phenotype, undifferentiated MSCs have high levels of hypoxia-inducible factor 1 (HIF-1). Osteogenically induced MSCs downregulate HIF-1 and this downregulation is required for activation of OxPhos. In summary, our work provides important insights on MSC bioenergetics and proposes a HIF-based mechanism of regulation of mitochondrial OxPhos in MSCs. PMID:26487485

  17. 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

  18. Bone-Marrow-Derived Mesenchymal Stem Cells for Organ Repair

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    Ming Li

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSCs are prototypical adult stem cells with the capacity for self-renewal and differentiation with a broad tissue distribution. MSCs not only differentiate into types of cells of mesodermal lineage but also into endodermal and ectodermal lineages such as bone, fat, cartilage and cardiomyocytes, endothelial cells, lung epithelial cells, hepatocytes, neurons, and pancreatic islets. MSCs have been identified as an adherent, fibroblast-like population and can be isolated from different adult tissues, including bone marrow (BM, umbilical cord, skeletal muscle, and adipose tissue. MSCs secrete factors, including IL-6, M-CSF, IL-10, HGF, and PGE2, that promote tissue repair, stimulate proliferation and differentiation of endogenous tissue progenitors, and decrease inflammatory and immune reactions. In this paper, we focus on the role of BM-derived MSCs in organ repair.

  19. Mesenchymal stem cells: a new trend for cell therapy

    Institute of Scientific and Technical Information of China (English)

    Xin WEI; Xue YANG; Zhi-peng HAN; Fang-fang QU; Li SHAO; Yu-fang SHI

    2013-01-01

    Mesenchymal stem cells (MSCs),the major stem cells for cell therapy,have been used in the clinic for approximately 10 years.From animal models to clinical trials,MSCs have afforded promise in the treatment of numerous diseases,mainly tissue injury and immune disorders.In this review,we summarize the recent opinions on methods,timing and cell sources for MSC administration in clinical applications,and provide an overview of mechanisms that are significant in MSC-mediated therapies.Although MSCs for cell therapy have been shown to be safe and effective,there are still challenges that need to be tackled before their wide application in the clinic.

  20. Mesenchymal stem cells and chronic renal artery stenosis.

    Science.gov (United States)

    Oliveira-Sales, Elizabeth B; Boim, Mirian A

    2016-01-01

    Renal artery stenosis is the main cause of renovascular hypertension and results in ischemic nephropathy characterized by inflammation, oxidative stress, microvascular loss, and fibrosis with consequent functional failure. Considering the limited number of strategies that effectively control renovascular hypertension and restore renal function, we propose that cell therapy may be a promising option based on the regenerative and immunosuppressive properties of stem cells. This review addresses the effects of mesenchymal stem cells (MSC) in an experimental animal model of renovascular hypertension known as 2 kidney-1 clip (2K-1C). Significant benefits of MSC treatment have been observed on blood pressure and renal structure of the stenotic kidney. The mechanisms involved are discussed.

  1. Mesenchymal Stem Cells and Nano-Bioceramics for Bone Regeneration.

    Science.gov (United States)

    Kankilic, Berna; Köse, Sevil; Korkusuz, Petek; Timuçin, Muharrem; Korkusuz, Feza

    Orthopedic disorders and trauma usually result in bone loss. Bone grafts are widely used to replace this tissue. Bone grafts excluding autografts unfortunately have disadvantages like evoking immune response, contamination and rejection. Autografts are of limited sources and optimum biomaterials that can replace bone have been searched for several decades. Bioceramics, which have the similar inorganic structure of natural bone, are widely used to regenerate bone or coat metallic implants. As people continuously look for a higher life quality, there are developments in technology almost everyday to meet their expectations. Nanotechnology is one of such technologies and it attracts everyone's attention in biomaterial science. Nano scale biomaterials have many advantages like larger surface area and higher biocompatibility and these properties make them more preferable than micro scale. Also, stem cells are used for bone regeneration besides nano-bioceramics due to their differentiation characteristics. This review covers current research on nano-bioceramics and mesenchymal stem cells and their role in bone regeneration.

  2. Therapeutic Implications of Mesenchymal Stem Cells in Liver Injury

    Directory of Open Access Journals (Sweden)

    Maria Ausiliatrice Puglisi

    2011-01-01

    Full Text Available Mesenchymal stem cells (MSCs, represent an attractive tool for the establishment of a successful stem-cell-based therapy of liver diseases. A number of different mechanisms contribute to the therapeutic effects exerted by MSCs, since these cells can differentiate into functional hepatic cells and can also produce a series of growth factors and cytokines able to suppress inflammatory responses, reduce hepatocyte apoptosis, regress liver fibrosis, and enhance hepatocyte functionality. To date, the infusion of MSCs or MSC-conditioned medium has shown encouraging results in the treatment of fulminant hepatic failure and in end-stage liver disease in experimental settings. However, some issues under debate hamper the use of MSCs in clinical trials. This paper summarizes the biological relevance of MSCs and the potential benefits and risks that can result from translating the MSC research to the treatment of liver diseases.

  3. A nanofibrous electrospun patch to maintain human mesenchymal cell stemness.

    Science.gov (United States)

    Pandolfi, L; Furman, N Toledano; Wang, Xin; Lupo, C; Martinez, J O; Mohamed, M; Taraballi, F; Tasciotti, E

    2017-03-01

    Mesenchymal stem cells (MSCs) have been extensively investigated in regenerative medicine because of their crucial role in tissue healing. For these properties, they are widely tested in clinical trials, usually injected in cell suspension or in combination with tridimensional scaffolds. However, scaffolds can largely affect the fates of MSCs, inducing a progressive loss of functionality overtime. The ideal scaffold must delay MSCs differentiation until paracrine signals from the host induce their change. Herein, we proposed a nanostructured electrospun gelatin patch as an appropriate environment where human MSCs (hMSCs) can adhere, proliferate, and maintain their stemness. This patch exhibited characteristics of a non-linear elastic material and withstood degradation up to 4 weeks. As compared to culture and expansion in 2D, hMSCs on the patch showed a similar degree of proliferation and better maintained their progenitor properties, as assessed by their superior differentiation capacity towards typical mesenchymal lineages (i.e. osteogenic and chondrogenic). Furthermore, immunohistochemical analysis and longitudinal non-invasive imaging of inflammatory response revealed no sign of foreign body reaction for 3 weeks. In summary, our results demonstrated that our biocompatible patch favored the maintenance of undifferentiated hMSCs for up to 21 days and is an ideal candidate for tridimensional delivery of hMSCs. The present work reports a nanostructured patch gelatin-based able to maintain in vitro hMSCs stemness features. Moreover, hMSCs were able to differentiate toward osteo- and chondrogenic lineages once induces by differentiative media, confirming the ability of this patch to support stem cells for a potential in vivo application. These attractive properties together with the low inflammatory response in vivo make this patch a promising platform in regenerative medicine.

  4. Development of bone marrow mesenchymal stem cell culture in vitro

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li; PENG Li-pan; WU Nan; LI Le-ping

    2012-01-01

    Objective To review the in vitro development of bone marrow mesenchymal stem cells culture (BM-MSC).Data sources The data cited in this review were mainly obtained from articles listed in Medline and PubMed.The search terms were “bone marrow mesenchymal stem cell" and "cell culture".Study selection Articles regarding the in vitro development of BM-MSCs culture,as well as the challenge of optimizing cell culture environment in two-dimensional (2D) vs.3D.Results Improving the culture conditions increases the proliferation and reduces the differentiation.Optimal values for many culture parameters remain to be identified.Expansion of BM-MSCs under defined conditions remains challenging,including the development of optimal culture conditions for BMSC and large-volume production systems.Conclusions Expansion of BM-MSCs under defined conditions remains challenges,including the development of optimal culture conditions for BMSC and scale-up to large-volume production systems.Optimal values for many culture parameters remain to be identified.

  5. Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

    Institute of Scientific and Technical Information of China (English)

    Justin; D; Glenn; Katharine; A; Whartenby

    2014-01-01

    Mesenchymal stem cells(MSCs) are a pleiotropic population of cells that are self-renewing and capable of differentiating into canonical cells of the mesenchyme, including adipocytes, chondrocytes, and osteocytes. They employ multi-faceted approaches to maintain bone marrow niche homeostasis and promote wound healing during injury. Biomedical research has long sought to exploit their pleiotropic properties as a basis for cell therapy for a variety of diseases and to facilitate hematopoietic stem cell establishment and stromal reconstruction in bone marrow transplantation. Early results demonstrated their usage as safe, and there was little host response to these cells. The discovery of their immunosuppressive functions ushered in a new interest in MSCs as a promising therapeutic tool to suppress inflammation and down-regulate pathogenic immune responses in graft-versus-host and autoimmune diseases such as multiple sclerosis, autoimmune diabetes, and rheumatoid arthritis. MSCs produce a large number of soluble and membrane-bound factors, some of which inhibit immune responses. However, the full range of MSC-mediated immune-modulation remains incompletely understood, as emerging reports also reveal that MSCs can adopt an immunogenic phenotype, stimulate immune cells, and yield seemingly contradictory results in experimental animal models of inflammatory disease. The present review describes the large body of literature that has been accumulated on the fascinating biology of MSCs and their complex effects on immune responses.

  6. Implications of mesenchymal stem cells in regenerative medicine.

    Science.gov (United States)

    Kariminekoo, Saber; Movassaghpour, Aliakbar; Rahimzadeh, Amirbahman; Talebi, Mehdi; Shamsasenjan, Karim; Akbarzadeh, Abolfazl

    2016-05-01

    Mesenchymal stem cells (MSCs) are a population of multipotent progenitors which reside in bone marrow, fat, and some other tissues and can be isolated from various adult and fetal tissues. Self-renewal potential and multipotency are MSC's hallmarks. They have the capacity of proliferation and differentiation into a variety of cell lineages like osteoblasts, condrocytes, adipocytes, fibroblasts, cardiomyocytes. MSCs can be identified by expression of some surface molecules like CD73, CD90, CD105, and lack of hematopoietic specific markers including CD34, CD45, and HLA-DR. They are hopeful tools for regenerative medicine for repairing injured tissues. Many studies have focused on two significant features of MSC therapy: (I) systemically administered MSCs home to sites of ischemia or injury, and (II) MSCs can modulate T-cell-mediated immunological responses. MSCs express chemokine receptors and ligands involved in cells migration and homing process. MSCs induce immunomedulatory effects on the innate (dendritic cells, monocyte, natural killer cells, and neutrophils) and the adaptive immune system cells (T helper-1, cytotoxic T lymphocyte, and B lymphocyte) by secreting soluble factors like TGF-β, IL-10, IDO, PGE-2, sHLA-G5, or by cell-cell interaction. In this review, we discuss the main applications of mesenchymal stem in Regenerative Medicine and known mechanisms of homing and Immunomodulation of MSCs.

  7. Induction of mesenchymal stem cell chondrogenesis by polyacrylate substrates.

    Science.gov (United States)

    Glennon-Alty, Laurence; Williams, Rachel; Dixon, Simon; Murray, Patricia

    2013-04-01

    Mesenchymal stem cells (MSCs) can generate chondrocytes in vitro, but typically need to be cultured as aggregates in the presence of transforming growth factor beta (TGF-β), which makes scale-up difficult. Here we investigated if polyacrylate substrates modelled on the functional group composition and distribution of the Arg-Gly-Asp (RGD) integrin-binding site could induce MSCs to undergo chondrogenesis in the absence of exogenous TGF-β. Within a few days of culture on the biomimetic polyacrylates, both mouse and human MSCs, and a mesenchymal-like mouse-kidney-derived stem cell line, began to form multi-layered aggregates and started to express the chondrocyte-specific markers, Sox9, collagen II and aggrecan. Moreover, collagen II tended to be expressed in the centre of the aggregates, similarly to developing limb buds in vivo. Surface analysis of the substrates indicated that those with the highest surface amine content were most effective at promoting MSC chondrogenesis. These results highlight the importance of surface group functionality and the distribution of those groups in the design of substrates to induce MSC chondrogenesis.

  8. Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.

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    Hongshan Liu

    Full Text Available BACKGROUND: Keratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation. METHODOLOGY/PRINCIPAL FINDINGS: Human mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice. CONCLUSIONS/SIGNIFICANCE: Umbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need.

  9. 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

  10. Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction

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    Chua Sarah

    2011-05-01

    Full Text Available Abstract Background Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury. Methods Adult male Sprague-Dawley (SD rats (n = 24 were equally randomized into group 1 (sham control, group 2 (IR plus culture medium only, and group 3 (IR plus immediate intra-renal administration of 1.0 × 106 autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR. The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed. Results Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p Conclusion ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response.

  11. Early combined treatment with sildenafil and adipose-derived mesenchymal stem cells preserves heart function in rat dilated cardiomyopathy

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    Fu Morgan

    2010-09-01

    Full Text Available Abstract Background We investigated whether early combined autologous adipose-derived mesenchymal stem cell (ADMSC and sildenafil therapy offers an additive benefit in preserving heart function in rat dilated cardiomyopathy (DCM. Methods Adult Lewis rats (n = 8 per group were divided into group 1 (normal control, group 2 (saline-treated DCM rats, group 3 [2.0 × 106 ADMSC implanted into left ventricular (LV myocardium of DCM rats], group 4 (DCM rats with sildenafil 30 mg/kg/day, orally, and group 5 (DCM rats with combined ADMSC-sildenafil. Treatment was started 1 week after DCM induction and the rats were sacrificed on day 90. Results The results showed that mitochondrial protein expressions of connexin43 and cytochrome-C were lowest in group 2, and lower in groups 3 and 4 than in group 5 (p Conclusion Early combined ADMSC/sildenafil is superior to either treatment alone in preserving LV function.

  12. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

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    Ya-jing Zhou

    2015-01-01

    Full Text Available Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  13. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Ya-jing Zhou; Jian-min Liu; Shu-ming Wei; Yun-hao Zhang; Zhen-hua Qu; Shu-bo Chen

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administrationvia the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve ifbers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and lfuorogold-labeled nerve ifbers were increased and hindlimb motor function of spinal cord-injured rats was mark-edly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  14. Characterization of mesenchymal stem cells in sheep naturally infected with scrapie.

    Science.gov (United States)

    Mediano, Diego R; Sanz-Rubio, David; Bolea, Rosa; Belén, Marín; Vázquez, Francisco J; Remacha, Ana R; López-Pérez, Oscar; Fernández-Borges, Natalia; Castilla, Joaquin; Zaragoza, Pilar

    2015-12-01

    Mesenchymal stem cells (MSCs) can be infected with prions and have been proposed as in vitro cell-based models for prion replication. In addition, autologous MSCs are of interest for cell therapy in neurodegenerative diseases. To the best of our knowledge, the effect of prion diseases on the characteristics of these cells has never been investigated. Here, we analysed the properties of MSCs obtained from bone marrow (BM-MSCs) and peripheral blood (PB-MSCs) of sheep naturally infected with scrapie — a large mammal model for the study of prion diseases. After three passages of expansion, MSCs derived from scrapie animals displayed similar adipogenic, chondrogenic and osteogenic differentiation ability as cells from healthy controls, although a subtle decrease in the proliferation potential was observed. Exceptionally, mesenchymal markers such as CD29 were significantly upregulated at the transcript level compared with controls. Scrapie MSCs were able to transdifferentiate into neuron-like cells, but displayed lower levels of neurogenic markers at basal conditions, which could limit this potential .The expression levels of cellular prion protein (PrPC) were highly variable between cultures, and no significant differences were observed between control and scrapie-derived MSCs. However, during neurogenic differentiation the expression of PrPC was upregulated in MSCs. This characteristic could be useful for developing in vitro models for prion replication. Despite the infectivity reported for MSCs obtained from scrapie-infected mice and Creutzfeldt–Jakob disease patients, protein misfolding cyclic amplification did not detect PrPSc in BM- or PB-MSCs from scrapie-infected sheep, which limits their use for in vivo diagnosis for scrapie.

  15. Clinical application of mesenchymal stem cells for aseptic bone necrosis

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    Tomoki Aoyama

    2008-11-01

    Full Text Available Since 2007, we had started clinical trial using mesenchymal stem cell (MSCs for the treatment of aseptic bone necrosis as a first clinical trial permitted by Japanese Health, Labour and Welfare Ministry.Aseptic bone necrosis of the femoral head commonly occurs in patients with two to four decades, causing severe musculoskeletal disability. Although its diagnosis is easy with X-ray and MRI, there has been no gold standard invented for treatment of this disease. MSCs represent a stem cell population in adult tissues that can be isolated and expanded in culture, and differentiate into cells with different nature. Combination with β-tri-calcium phosphate and vascularized bone graft, we succeeded to treat bone necrosis of the femoral head.Regenerative medicine using stem cells is hopeful and shed a light on intractable disease. To become widespread, Basic, Translational, Application, and Developmental study is needed.? From an experience of cell therapy using MSCs, we started to research induced pluripotent stem cell (iPS for clinical application.

  16. Dedifferentiation-reprogrammed mesenchymal stem cells with improved therapeutic potential.

    Science.gov (United States)

    Liu, Yang; Jiang, Xiaohua; Zhang, Xiaohu; Chen, Rui; Sun, Tingting; Fok, Kin Lam; Dong, Jianda; Tsang, Lai Ling; Yi, Shaoqiong; Ruan, Yechun; Guo, Jinghui; Yu, Mei Kuen; Tian, Yuemin; Chung, Yiu Wa; Yang, Mo; Xu, Wenming; Chung, Chin Man; Li, Tingyu; Chan, Hsiao Chang

    2011-12-01

    Stem cell transplantation has been shown to improve functional outcome in degenerative and ischemic disorders. However, low in vivo survival and differentiation potential of the transplanted cells limits their overall effectiveness and thus clinical usage. Here we show that, after in vitro induction of neuronal differentiation and dedifferentiation, on withdrawal of extrinsic factors, mesenchymal stem cells (MSCs) derived from bone marrow, which have already committed to neuronal lineage, revert to a primitive cell population (dedifferentiated MSCs) retaining stem cell characteristics but exhibiting a reprogrammed phenotype distinct from their original counterparts. Of therapeutic interest, the dedifferentiated MSCs exhibited enhanced cell survival and higher efficacy in neuronal differentiation compared to unmanipulated MSCs both in vitro and in vivo, with significantly improved cognition function in a neonatal hypoxic-ischemic brain damage rat model. Increased expression of bcl-2 family proteins and microRNA-34a appears to be the important mechanism giving rise to this previously undefined stem cell population that may provide a novel treatment strategy with improved therapeutic efficacy.

  17. Mechanisms Underlying the Osteo- and Adipo-Differentiation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2012-01-01

    Full Text Available Human mesenchymal stem cells (hMSCs are considered a promising cell source for regenerative medicine, because they have the potential to differentiate into a variety of lineages among which the mesoderm-derived lineages such adipo- or osteogenesis are investigated best. Human MSCs can be harvested in reasonable to large amounts from several parts of the patient’s body and due to this possible autologous origin, allorecognition can be avoided. In addition, even in allogenic origin-derived donor cells, hMSCs generate a local immunosuppressive microenvironment, causing only a weak immune reaction. There is an increasing need for bone replacement in patients from all ages, due to a variety of reasons such as a new recreational behavior in young adults or age-related diseases. Adipogenic differentiation is another interesting lineage, because fat tissue is considered to be a major factor triggering atherosclerosis that ultimately leads to cardiovascular diseases, the main cause of death in industrialized countries. However, understanding the differentiation process in detail is obligatory to achieve a tight control of the process for future clinical applications to avoid undesired side effects. In this review, the current findings for adipo- and osteo-differentiation are summarized together with a brief statement on first clinical trials.

  18. Chondrocytes, Mesenchymal Stem Cells, and Their Combination in Articular Cartilage Regenerative Medicine.

    Science.gov (United States)

    Nazempour, A; Van Wie, B J

    2016-05-01

    Articular cartilage (AC) is a highly organized connective tissue lining, covering the ends of bones within articulating joints. Its highly ordered structure is essential for stable motion and provides a frictionless surface easing load transfer. AC is vulnerable to lesions and, because it is aneural and avascular, it has limited self-repair potential which often leads to osteoarthritis. To date, no fully successful treatment for osteoarthritis has been reported. Thus, the development of innovative therapeutic approaches is desperately needed. Autologous chondrocyte implantation, the only cell-based surgical intervention approved in the United States for treating cartilage defects, has limitations because of de-differentiation of articular chondrocytes (AChs) upon in vitro expansion. De-differentiation can be abated if initial populations of AChs are co-cultured with mesenchymal stem cells (MSCs), which not only undergo chondrogenesis themselves but also support chondrocyte vitality. In this review we summarize studies utilizing AChs, non-AChs, and MSCs and compare associated outcomes. Moreover, a comprehensive set of recent human studies using chondrocytes to direct MSC differentiation, MSCs to support chondrocyte re-differentiation and proliferation in co-culture environments, and exploratory animal intra- and inter-species studies are systematically reviewed and discussed in an innovative manner allowing side-by-side comparisons of protocols and outcomes. Finally, a comprehensive set of recommendations are made for future studies.

  19. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, J.C. [Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China); Zheng, G.F. [Department of Vascular Surgery, The People' s Hospital of Ganzhou, Ganzhou (China); Wu, L.; Ou Yang, L.Y.; Li, W.X. [Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou (China)

    2014-08-08

    Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

  20. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

    Directory of Open Access Journals (Sweden)

    J.C. Zhang

    2014-10-01

    Full Text Available Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs expressing human basic fibroblast growth factor (hbFGF. After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC, MSCs expressing hbFGF (hbFGF-MSC, MSC controls, and phosphate-buffered saline (PBS controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001; however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008 and microvessel density (P<0.001. Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

  1. Mesenchymal Stem/Stromal Cells from Discarded Neonatal Sternal Tissue: In Vitro Characterization and Angiogenic Properties

    Directory of Open Access Journals (Sweden)

    Shuyun Wang

    2016-01-01

    Full Text Available Autologous and nonautologous bone marrow mesenchymal stem/stromal cells (MSCs are being evaluated as proangiogenic agents for ischemic and vascular disease in adults but not in children. A significant number of newborns and infants with critical congenital heart disease who undergo cardiac surgery already have or are at risk of developing conditions related to inadequate tissue perfusion. During neonatal cardiac surgery, a small amount of sternal tissue is usually discarded. Here we demonstrate that MSCs can be isolated from human neonatal sternal tissue using a nonenzymatic explant culture method. Neonatal sternal bone MSCs (sbMSCs were clonogenic, had a surface marker expression profile that was characteristic of bone marrow MSCs, were multipotent, and expressed pluripotency-related genes at low levels. Neonatal sbMSCs also demonstrated in vitro proangiogenic properties. Sternal bone MSCs cooperated with human umbilical vein endothelial cells (HUVECs to form 3D networks and tubes in vitro. Conditioned media from sbMSCs cultured in hypoxia also promoted HUVEC survival and migration. Given the neonatal source, ease of isolation, and proangiogenic properties, sbMSCs may have relevance to therapeutic applications.

  2. Mesenchymal Stem Cells for Regenerative Therapy: Optimization of Cell Preparation Protocols

    Directory of Open Access Journals (Sweden)

    Chiho Ikebe

    2014-01-01

    Full Text Available Administration of bone marrow-derived mesenchymal stem cells (MSCs is an innovative approach for the treatment of a range of diseases that are not curable by current therapies including heart failure. A number of clinical trials have been completed and many others are ongoing; more than 2,000 patients worldwide have been administered with culture-expanded allogeneic or autologous MSCs for the treatment of various diseases, showing feasibility and safety (and some efficacy of this approach. However, protocols for isolation and expansion of donor MSCs vary widely between these trials, which could affect the efficacy of the therapy. It is therefore important to develop international standards of MSC production, which should be evidence-based, regulatory authority-compliant, of good medical practice grade, cost-effective, and clinically practical, so that this innovative approach becomes an established widely adopted treatment. This review article summarizes protocols to isolate and expand bone marrow-derived MSCs in 47 recent clinical trials of MSC-based therapy, which were published after 2007 onwards and provided sufficient methodological information. Identified issues and possible solutions associated with the MSC production methods, including materials and protocols for isolation and expansion, are discussed with reference to relevant experimental evidence with aim of future clinical success of MSC-based therapy.

  3. Mesenchymal stem cells as a potent cell source for articular cartilage regeneration

    Institute of Scientific and Technical Information of China (English)

    Mohamadreza; Baghaban; Eslaminejad; Elham; Malakooty; Poor

    2014-01-01

    Since articular cartilage possesses only a weak capac-ity for repair, its regeneration potential is considered one of the most important challenges for orthopedic surgeons. The treatment options, such as marrow stimulation techniques, fail to induce a repair tissue with the same functional and mechanical properties of native hyaline cartilage. Osteochondral transplantation is considered an effective treatment option but is as-sociated with some disadvantages, including donor-site morbidity, tissue supply limitation, unsuitable mechani-cal properties and thickness of the obtained tissue. Although autologous chondrocyte implantation results in reasonable repair, it requires a two-step surgical pro-cedure. Moreover, chondrocytes expanded in culture gradually undergo dedifferentiation, so lose morpho-logical features and specialized functions. In the search for alternative cells, scientists have found mesenchymal stem cells(MSCs) to be an appropriate cellular mate-rial for articular cartilage repair. These cells were origi-nally isolated from bone marrow samples and further investigations have revealed the presence of the cells in many other tissues. Furthermore, chondrogenic dif-ferentiation is an inherent property of MSCs noticedat the time of the cell discovery. MSCs are known to exhibit homing potential to the damaged site at which they differentiate into the tissue cells or secrete a wide spectrum of bioactive factors with regenerative proper-ties. Moreover, these cells possess a considerable im-munomodulatory potential that make them the general donor for therapeutic applications. All of these topics will be discussed in this review.

  4. Preliminary Observation on the Influence of Tumor Osseous Metastasis on Autologous Peripheral Blood Stem Cell Collection

    Institute of Scientific and Technical Information of China (English)

    Xiaoming Si; Wenchao Liu; Yan Xue; Hongmei Zhang; Rong Sheng; Ying Huang; Jie Cheng

    2007-01-01

    OBJECTIVE To examine the influence of tumor osseous metastasis on the patients undergoing autologous peripheral blood stem cell collection. METHODS A total of 36 patients with malignant diseases who received an autologous peripheral blood stem cell transplantation, during a period from April 2004 to June 2006, were chosen. The patients were divided into two groups, I.e. Group A were patients with a complication of tumor osseous metastasis, and group B were without metastasis. Both groups were treated with Taxotere 120 mg/m2 plus granulocyte colony-stimulating factor (G-CSF) 5 ug/kg/d, for a mobilization regimen. A blood cell separator was used to collect the mononuclear cells. The proportion of harvested CD34+ cells in the peripheral blood and the collected mononuclear cells were detected by flow cytometry. The number of CD34+ cells was used to determine the difference in the nature of the collections between the two groups. RESULTS After mobilization in groups A and B, the number of the peripheral blood mononuclear cells (PBMC) was 39.3 ±14.7% and 41.±12.4 % and the proportion of CD34 + cells was 0.16±0.07% and 0.17 ± 0.10%, respectively. Following administration of the drugs, there was no significant difference between the number of harvested PBMC and CD34+ cells of the two groups, I.e., 3.47 ± 1.16 x 108/Kg and 2.52 ± 1.43 × 106/Kg in group A and 4.02 ± 1.31 × 108/Kg and 2.73 ± 1.87 x 108/Kg in group B, respectively. CONCLUSION Osseous metastasis, as a single factor, may have no impact on mobilization and harvesting of hematopoietic stem cells and their engraftment after autotransplantation.

  5. Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma

    DEFF Research Database (Denmark)

    Andersen, Niels S; Pedersen, Lone B; Laurell, Anna

    2009-01-01

    PURPOSE: Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell...

  6. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial

    NARCIS (Netherlands)

    Laar, J.M. van; Farge, D.; Sont, J.K.; Naraghi, K.; Marjanovic, Z.; Larghero, J.; Schuerwegh, A.J.; Marijt, E.W.; Vonk, M.C.; Schattenberg, A.V.M.B.; Matucci-Cerinic, M.; Voskuyl, A.E.; Loosdrecht, A.A. van de; Daikeler, T.; Kotter, I.; Schmalzing, M.; Martin, T.; Lioure, B.; Weiner, S.M.; Kreuter, A.; Deligny, C.; Durand, J.M.; Emery, P.; Machold, K.P.; Sarrot-Reynauld, F.; Warnatz, K.; Adoue, D.F.; Constans, J.; Tony, H.P.; Papa, N. Del; Fassas, A.; Himsel, A.; Launay, D. de; Monaco, A. Lo; Philippe, P.; Quere, I.; Rich, E.; Westhovens, R.; Griffiths, B.; Saccardi, R.; Hoogen, F.H.J. van den; Fibbe, W.E.; Socie, G.; Gratwohl, A.; Tyndall, A.

    2014-01-01

    IMPORTANCE: High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. OBJECTIVE: To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphami

  7. Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT

    DEFF Research Database (Denmark)

    Grövdal, M; Nahi, H; Gahrton, G;

    2015-01-01

    High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common first-line treatment for patients with multiple myeloma (MM) under 65 years of age. A second ASCT at first relapse is frequently used but is challenged by the use of novel drugs. We retrospectively...

  8. Myogenic differentiation of mesenchymal stem cells for muscle regeneration in urinary tract

    Institute of Scientific and Technical Information of China (English)

    YANG Bin; ZHENG Jun-hua; ZHANG Yuan-yuan

    2013-01-01

    Objective This article was to review the current status of adult mesenchymal stem cells transplantation for muscle regeneration in urinary tract and propose the future prospect in this field.Data sources The data used in this review were mainly obtained from articles listed in Medline and PubMed (2000-2013).The search terms were "mesenchymal stem cells","bladder","stress urinary incontinence" and "tissue engineering".Study selection Articles regarding the adult mesenchymal stem cells for tissue engineering of bladder and stress urinary incontinence were selected and reviewed.Results Adult mesenchymal stem cells had been identified and well characterized in human bone marrow,adipose tissue,skeletal muscle and urine,and demonstrated the capability of differentiating into smooth muscle cells and skeletal muscle cells under myogenic differentiation conditions in vitro.Multiple preclinical and clinical studies indicated that adult mesenchymal stem cells could restore and maintain the structure and function of urinary muscle tissues after transplanted,and potentially improve the quality of life in patients.Conclusions Smooth or skeletal myogenic differentiation of mesenchymal stem cells with regenerative medicine technology may provide a novel approach for muscle regeneration and tissue repair in urinary tract.The long-term effect and safety of mesenchymal stem cell transplantation should be further evaluated before this approach becomes widely used in patients.

  9. RNA-Seq Reveals the Angiogenesis Diversity between the Fetal and Adults Bone Mesenchyme Stem Cell.

    Science.gov (United States)

    Zhao, Xin; Han, Yingmin; Liang, Yu; Nie, Chao; Wang, Jian

    2016-01-01

    In this research, we used RNA sequencing (RNA-seq) to analyze 23 single cell samples and 2 bulk cells sample from human adult bone mesenchyme stem cell line and human fetal bone mesenchyme stem cell line. The results from the research demonstrated that there were big differences between two cell lines. Adult bone mesenchyme stem cell lines showed a strong trend on the blood vessel differentiation and cell motion, 48/49 vascular related differential expressed genes showed higher expression in adult bone mesenchyme stem cell lines (Abmsc) than fetal bone mesenchyme stem cell lines (Fbmsc). 96/106 cell motion related genes showed the same tendency. Further analysis showed that genes like ANGPT1, VEGFA, FGF2, PDGFB and PDGFRA showed higher expression in Abmsc. This work showed cell heterogeneity between human adult bone mesenchyme stem cell line and human fetal bone mesenchyme stem cell line. Also the work may give an indication that Abmsc had a better potency than Fbmsc in the future vascular related application.

  10. Mesenchymal stem cell therapy for osteoarthritis: current perspectives

    Directory of Open Access Journals (Sweden)

    Wyles CC

    2015-08-01

    Full Text Available Cody C Wyles,1 Matthew T Houdek,2 Atta Behfar,3 Rafael J Sierra,21Mayo Medical School, 2Department of Orthopedic Surgery, 3Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USAAbstract: Osteoarthritis (OA is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.Keywords: mesenchymal stem cell, osteoarthritis, treatment, regenerative medicine, cell therapy

  11. In vitro fabrication of autologous living tissue-engineered vascular grafts based on prenatally harvested ovine amniotic fluid-derived stem cells.

    Science.gov (United States)

    Weber, Benedikt; Kehl, Debora; Bleul, Ulrich; Behr, Luc; Sammut, Sébastien; Frese, Laura; Ksiazek, Agnieszka; Achermann, Josef; Stranzinger, Gerald; Robert, Jérôme; Sanders, Bart; Sidler, Michele; Brokopp, Chad E; Proulx, Steven T; Frauenfelder, Thomas; Schoenauer, Roman; Emmert, Maximilian Y; Falk, Volkmar; Hoerstrup, Simon P

    2016-01-01

    Amniotic fluid cells (AFCs) have been proposed as a valuable source for tissue engineering and regenerative medicine. However, before clinical implementation, rigorous evaluation of this cell source in clinically relevant animal models accepted by regulatory authorities is indispensable. Today, the ovine model represents one of the most accepted preclinical animal models, in particular for cardiovascular applications. Here, we investigate the isolation and use of autologous ovine AFCs as cell source for cardiovascular tissue engineering applications. Fetal fluids were aspirated in vivo from pregnant ewes (n = 9) and from explanted uteri post mortem at different gestational ages (n = 91). Amniotic non-allantoic fluid nature was evaluated biochemically and in vivo samples were compared with post mortem reference samples. Isolated cells revealed an immunohistochemical phenotype similar to ovine bone marrow-derived mesenchymal stem cells (MSCs) and showed expression of stem cell factors described for embryonic stem cells, such as NANOG and STAT-3. Isolated ovine amniotic fluid-derived MSCs were screened for numeric chromosomal aberrations and successfully differentiated into several mesodermal phenotypes. Myofibroblastic ovine AFC lineages were then successfully used for the in vitro fabrication of small- and large-diameter tissue-engineered vascular grafts (n = 10) and cardiovascular patches (n = 34), laying the foundation for the use of this relevant pre-clinical in vivo assessment model for future amniotic fluid cell-based therapeutic applications.

  12. Spinal fusion of lumbar intertransverse process in rabbits using two different densities of autologous marrow mesenchymal stem cells combined with β-TCP%两种接种密度骨髓基质干细胞复合β-TCP对兔腰椎横突间融合的效果

    Institute of Scientific and Technical Information of China (English)

    潘玮敏; 胡蕴玉; 陈俊伟; 郑芬芳; 郑振耀; 毕龙

    2009-01-01

    [目的]观察两种不同接种密度的骨髓基质干细胞(bone marrow mesenchymal stem cells ,BMSCs),在成骨诱导分化后复合β-TCP应用于兔腰椎横突间脊柱融合的术后融合效果.[方法]应用BMSCs/β-TCP复合体对随机分为两组(低密度接种组和高密度接种组)的实验兔进行腰椎横突间非去皮质骨脊柱融合术,观察两组动物术后大体腰椎融合率、影像学特征、骨矿含量(bone mineralization content,BMC),骨密度(bone mineralization density,BMD)和矿化组织体积(bone mineralization tissue volume,BMV)及组织形态学变化.[结果]与低密度接种组比较,高密度接种组术后融合率明显提高,可达到71.4%(P<0.05).显微CT图像结果显示高密度接种组横突间不仅新骨形成量多,而且融合稳固,且其BMC、BMD和BMV及新骨生成率均高于低密度接种组(P<0.05).[结论]使用接种密度为10×106 cells/ ml的人工骨具有较好的融合效果,融合率可达到71.4%,这一点为临床应用BMSCs复合生物材料体外构建人工骨应用于非去皮质骨脊柱后路融合有一定的指导意义.

  13. Advances of mesenchymal stem cells derived from bone marrow and dental tissue in craniofacial tissue engineering.

    Science.gov (United States)

    Yang, Maobin; Zhang, Hongming; Gangolli, Riddhi

    2014-05-01

    Bone and dental tissues in craniofacial region work as an important aesthetic and functional unit. Reconstruction of craniofacial tissue defects is highly expected to ensure patients to maintain good quality of life. Tissue engineering and regenerative medicine have been developed in the last two decades, and been advanced with the stem cell technology. Bone marrow derived mesenchymal stem cells are one of the most extensively studied post-natal stem cell population, and are widely utilized in cell-based therapy. Dental tissue derived mesenchymal stem cells are a relatively new stem cell population that isolated from various dental tissues. These cells can undergo multilineage differentiation including osteogenic and odontogenic differentiation, thus provide an alternative source of mesenchymal stem cells for tissue engineering. In this review, we discuss the important issues in mesenchymal stem cell biology including the origin and functions of mesenchymal stem cells, compare the properties of these two types of mesenchymal cells, update recent basic research and clinic applications in this field, and address important future challenges.

  14. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis.

    Science.gov (United States)

    Gorin, Norbert-Claude; Labopin, Myriam; Piemontese, Simona; Arcese, William; Santarone, Stella; Huang, He; Meloni, Giovanna; Ferrara, Felicetto; Beelen, Dietrich; Sanz, Miguel; Bacigalupo, Andrea; Ciceri, Fabio; Mailhol, Audrey; Nagler, Arnon; Mohty, Mohamad

    2015-04-01

    Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. "Haploidentical expert" centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes ("haploidentical regular", "haploidentical expert" and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; Ptransplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program.

  15. Characterization of mesenchymal stem cells derived from equine adipose tissue

    Directory of Open Access Journals (Sweden)

    A.M. Carvalho

    2013-08-01

    Full Text Available Stem cell therapy has shown promising results in tendinitis and osteoarthritis in equine medicine. The purpose of this work was to characterize the adipose-derived mesenchymal stem cells (AdMSCs in horses through (1 the assessment of the capacity of progenitor cells to perform adipogenic, osteogenic and chondrogenic differentiation; and (2 flow cytometry analysis using the stemness related markers: CD44, CD90, CD105 and MHC Class II. Five mixed-breed horses, aged 2-4 years-old were used to collect adipose tissue from the base of the tail. After isolation and culture of AdMSCs, immunophenotypic characterization was performed through flow cytometry. There was a high expression of CD44, CD90 and CD105, and no expression of MHC Class II markers. The tri-lineage differentiation was confirmed by specific staining: adipogenic (Oil Red O, osteogenic (Alizarin Red, and chondrogenic (Alcian Blue. The equine AdMSCs are a promising type of adult progenitor cell for tissue engineering in veterinary medicine.

  16. Guidance of mesenchymal stem cells on fibronectin structured hydrogel films.

    Directory of Open Access Journals (Sweden)

    Annika Kasten

    Full Text Available Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN that was homogeneously immmobilized to NCO-sP(EO-stat-PO, which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 µm and 80 µm and spacings between 5 µm and 20 µm that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration.

  17. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANT IN FOLLICULAR LYMPHOMAS

    Directory of Open Access Journals (Sweden)

    Mónica Cabrero

    2012-11-01

    Full Text Available Follicular lymphoma (FL remains incurable despite advances in new strategies of treatment, including monoclonal antibodies (MoAb. Except for early stages, FL is characterized by responses to treatments and systematic relapses. The main objective in this disease is to achieve a better progression free survival (PFS and to increase overall survival (OS, mainly in young patients. In order to improve the results of conventional chemotherapy, autologous stem cell transplant (ASCT is a feasible treatment in these patients. In this moment, ASCT is not recommended as first line treatment, except for transformed FL, but is a good strategy as salvage therapy with an improved PFS and OS. New drugs have been introduced to enhance responses of ASCT, but nowadays they are not part of conventional conditioning regimen.

  18. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANT IN FOLLICULAR LYMPHOMAS

    Directory of Open Access Journals (Sweden)

    Mónica Cabrero

    2012-01-01

    Full Text Available

    Follicular lymphoma (FL remains incurable despite advances in new strategies of treatment, including monoclonal antibodies (MoAb. Except for early stages, FL is characterized by responses to treatments and systematic relapses. The main objective in this disease is to achieve a better progression free survival (PFS and to increase overall survival (OS, mainly in young patients. In order to improve the results of conventional chemotherapy, autologous stem cell transplant (ASCT is a feasible treatment in these patients. In this moment, ASCT is not recommended as first line treatment, except for transformed FL, but is a good strategy as salvage therapy with an improved PFS and OS. New drugs have been introduced to enhance responses of ASCT, but nowadays they are not part of conventional conditioning regimen.

  19. Update on the Role of Autologous Hematopoietic Stem Cell Transplantation in Follicular Lymphoma

    Science.gov (United States)

    Cabrero, Mónica; Redondo, Alba; Martin, Alejandro; Caballero, Dolores

    2012-01-01

    Follicular lymphoma (FL) remains incurable despite advances in new strategies of treatment, including monoclonal antibodies (MoAb). Except for early stages, FL is characterized by responses to treatments and systematic relapses. The main objective in this disease is to achieve a better progression free survival (PFS) and to increase overall survival (OS), mainly in young patients. In order to improve the results of conventional chemotherapy, autologous stem cell transplant (ASCT) is a feasible treatment in these patients. In this moment, ASCT is not recommended as first line treatment, except for transformed FL, but is a good strategy as salvage therapy with an improved PFS and OS. New drugs have been introduced to enhance responses of ASCT, but nowadays they are not part of conventional conditioning regimen. PMID:23205262

  20. Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis.

    Science.gov (United States)

    Jiang, Nan; Zhou, Jian; Chen, Mo; Schiff, Michael D; Lee, Chang H; Kong, Kimi; Embree, Mildred C; Zhou, Yanheng; Mao, Jeremy J

    2014-02-01

    Rodent incisors provide a classic model for studying epithelial-mesenchymal interactions in development. However, postnatal stem/progenitor cells in rodent incisors have not been exploited for tooth regeneration. Here, we characterized postnatal rat incisor epithelium and mesenchyme stem/progenitor cells and found that they formed enamel- and dentin-like tissues in vivo. Epithelium and mesenchyme cells were harvested separately from the apical region of postnatal 4-5 day rat incisors. Epithelial and mesenchymal phenotypes were confirmed by immunocytochemistry, CFU assay and/or multi-lineage differentiation. CK14+, Sox2+ and Lgr5+ epithelium stem cells from the cervical loop enhanced amelogenin and ameloblastin expression upon BMP4 or FGF3 stimulation, signifying their differentiation towards ameloblast-like cells, whereas mesenchyme stem/progenitor cells upon BMP4, BMP7 and Wnt3a treatment robustly expressed Dspp, a hallmark of odontoblastic differentiation. We then control-released microencapsulated BMP4, BMP7 and Wnt3a in transplants of epithelium and mesenchyme stem/progenitor cells in the renal capsule of athymic mice in vivo. Enamel and dentin-like tissues were generated in two integrated layers with specific expression of amelogenin and ameloblastin in the newly formed, de novo enamel-like tissue, and DSP in dentin-like tissue. These findings suggest that postnatal epithelium and mesenchyme stem/progenitor cells can be primed towards bioengineered tooth regeneration.

  1. Runx2 expression: A mesenchymal stem marker for cancer

    Science.gov (United States)

    Valenti, Maria Teresa; Serafini, Paola; Innamorati, Giulio; Gili, Anna; Cheri, Samuele; Bassi, Claudio; Dalle Carbonare, Luca

    2016-01-01

    The transcription factor runt-related transcription factor 2 (Runx2) is a master gene implicated in the osteogenic differentiation of mesenchymal stem cells, and thus serves a determinant function in bone remodelling and skeletal integrity. Various signalling pathways regulate Runx2 abundance, which requires a number of molecules to finely modulate its expression. Furthermore, this gene may be ectopically-expressed in cancer cells. Recent studies have reported the involvement of Runx2 in cell proliferation, epithelial-mesenchymal transition, apoptosis and metastatic processes, suggesting it may represent a useful therapeutic target in cancer treatment. However, studies evaluating this gene as a cancer marker are lacking. In the present study, Runx2 expression was analysed in 11 different cancer cell lines not derived from bone tumour. In addition, the presence of Runx2-related cell-free RNA was examined in the peripheral blood of 41 patients affected by different forms of tumours. The results demonstrated high expression levels of Runx2 in the cancer cell lines and identified the presence of Runx2-related cell-free RNA in the peripheral blood of patients with cancer. As compared with normal individuals, the expression level was increased by 14.2-fold in patients with bone metastases and by 4.01-fold in patients without metastases. The results of the present study therefore opens up the possibility to exploit Runx2 expression as a cancer biomarker allowing the use of minimally invasive approaches for diagnosis and follow-up. PMID:27895787

  2. Expanded autologous adipose derived stem cell transplantation for type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Phuong Thi-Bich Le

    2016-12-01

    Full Text Available Introduction: Type 2 diabetes mellitus (T2D is the most common form of diabetes mellitus, accounting for 90% of diabetes mellitus in patients. At the present time, althoughT2D can be treated by various drugs and therapies using insulin replacement, reports have shown that complications including microvascular, macrovascular complications and therapy resistance can occur in patients on long term treatment. Stem cell therapy is regarded as a promising therapy for diabetes mellitus, including T2D. The aim of this study was to evaluate the safety and therapeutic effect of expanded autologous adipose derived stem cell (ADSC transplantation for T2D treatment; the pilot study included 3 patients who were followed for 3 months. Methods: The ADSCs were isolated from stromal vascular fractions, harvested from the belly of the patient,and expanded for 21 days per previously published studies. Before transplantation, ADSCs were evaluated for endotoxin, mycoplasma contamination, and karyotype.All patients were transfused with ADSCs at 1-2x106 cells/kg of body weight.Patients were evaluated for criteria related to transplantation safety and therapeutic effects; these included fever, blood glucose level before transplantation of ADSCs, and blood glucose level after transplantation (at 1, 2 and 3 months. Results: The results showed that all samples of ADSCs exhibited the MSC phenotype with stable karyotype (2n=46, there was no contamination of mycoplasma, and endotoxin levels were low (<0.25 EU/mL. No adverse effects were detected after 3 months of transplantation. Decreases of blood glucose levels were recorded in all patients. Conclusion: The findings from this initial study show that expanded autologous ADSCs may be a promising treatment for T2D.

  3. Chemical injury treated with autologous limbal epithelial stem cell transplantation and subconjunctival bevacizumab

    Directory of Open Access Journals (Sweden)

    Cavallini GM

    2014-08-01

    Full Text Available Gian Maria Cavallini,1 Graziella Pellegrini,2 Veronica Volante,1 Pietro Ducange,1 Michele De Maria,1 Giulio Torlai,1 Caterina Benatti,1 Matteo Forlini1 1Institute of Ophthalmology, 2Centre for Regenerative Medicine “Stefano Ferrari”, University of Modena e Reggio Emilia, Modena, Italy Background: Limbal stem cell (LSC deficiency leads to corneal opacity due to a conjunctivalization of the corneal surface. LSC transplantation, which can be followed by corneal keratoplasty, is an effective procedure to restore corneal transparency; however, a common cause of failure of this procedure is neovascularization (NV.Methods: A 59-year-old man with a 21-year history of a corneal chemical burn caused by phosphoric acid in his left eye was examined. He presented with unilateral total LSC deficiency with severe conjunctivalization and a corrected distance visual acuity that was limited to hand motion.Results: We reported the short-term in vivo efficacy of subconjunctival bevacizumab for progressive corneal NV in a patient with LSC deficiency that underwent LSC transplantation. Four months after autologous LSC transplantation and 1 month after the second subconjunctival bevacizumab injection, the patient’s corrected distance visual acuity was 1/10.Conclusion: Subconjunctival injection of bevacizumab can reduce the corneal NV, reducing conjunctival inflammation and supporting restoration of a stable ocular surface that is able to counteract graft failure, with no toxicity for the transplanted LSC. Keywords: stem cells, bevacizumab, limbal stem cell deficiency, transplantation

  4. [Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases].

    Science.gov (United States)

    Sánchez-Berná, Isabel; Santiago-Díaz, Carlos; Jiménez-Alonso, Juan

    2015-01-20

    Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use.

  5. Mesenchymal Stem Cells after Polytrauma: Actor and Target

    Directory of Open Access Journals (Sweden)

    Markus Huber-Lang

    2016-01-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent cells that are considered indispensable in regeneration processes after tissue trauma. MSCs are recruited to damaged areas via several chemoattractant pathways where they function as “actors” in the healing process by the secretion of manifold pro- and anti-inflammatory, antimicrobial, pro- and anticoagulatory, and trophic/angiogenic factors, but also by proliferation and differentiation into the required cells. On the other hand, MSCs represent “targets” during the pathophysiological conditions after severe trauma, when excessively generated inflammatory mediators, complement activation factors, and damage- and pathogen-associated molecular patterns challenge MSCs and alter their functionality. This in turn leads to complement opsonization, lysis, clearance by macrophages, and reduced migratory and regenerative abilities which culminate in impaired tissue repair. We summarize relevant cellular and signaling mechanisms and provide an up-to-date overview about promising future therapeutic MSC strategies in the context of severe tissue trauma.

  6. Good manufacturing practices production of mesenchymal stem/stromal cells.

    Science.gov (United States)

    Sensebé, Luc; Bourin, Philippe; Tarte, Karin

    2011-01-01

    Because of their multi/pluripotency and immunosuppressive properties mesenchymal stem/stromal cells (MSCs) are important tools for treating immune disorders and for tissue repair. The increasing use of MSCs has led to production processes that need to be in accordance with Good Manufacturing Practice (GMP). In cellular therapy, safety remains one of the main concerns and refers to donor validation, choice of starting material, processes, and the controls used, not only at the batch release level but also during the development of processes. The culture processes should be reproducible, robust, and efficient. Moreover, they should be adapted to closed systems that are easy to use. Implementing controls during the manufacturing of clinical-grade MSCs is essential. The controls should ensure microbiological safety but also avoid potential side effects linked to genomic instability driving transformation and senescence or decrease of cell functions (immunoregulation, differentiation potential). In this rapidly evolving field, a new approach to controls is needed.

  7. Mesenchymal stem cells as a therapeutic tool to treat sepsis

    Institute of Scientific and Technical Information of China (English)

    Eleuterio Lombardo; Tom van der Poll; Olga DelaRosa; Wilfried Dalemans

    2015-01-01

    Sepsis is a clinical syndrome caused by a deregulatedhost response to an infection. Sepsis is the mostfrequent cause of death in hospitalized patients.Although knowledge of the pathogenesis of sepsishas increased substantially during the last decades,attempts to design effective and specific therapiestargeting components of the derailed host responsehave failed. Therefore, there is a dramatic need fornew and mechanistically alternative therapies to treatthis syndrome. Based on their immunomodulatoryproperties, adult mesenchymal stem or stromal cells(MSCs) can be a novel therapeutic tool to treat sepsis.Indeed, MSCs reduce mortality in experimental modelsof sepsis by modulating the deregulated inflammatoryresponse against bacteria through the regulation ofmultiple inflammatory networks, the reprogrammingof macrophages and neutrophils towards a more antiinflammatoryphenotype and the release of antimicrobialpeptides. This report will review the currentknowledge on the effects of MSC treatment in preclinicalexperimental small animal models of sepsis.

  8. 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.

  9. Circulating mesenchymal stem cells and their clinical implications

    Directory of Open Access Journals (Sweden)

    Liangliang Xu

    2014-01-01

    Full Text Available Circulating mesenchymal stem cells (MSCs is a new cell source for tissue regeneration and tissue engineering. The characteristics of circulating MSCs are similar to those of bone marrow-derived MSCs (BM-MSCs, but they exist at a very low level in healthy individuals. It has been demonstrated that MSCs are able to migrate to the sites of injury and that they have some distinct genetic profiles compared to BM-MSCs. The current review summaries the basic knowledge of circulating MSCs and their potential clinical applications, such as mobilizing the BM-MSCs into circulation for therapy. The application of MSCs to cure a broad spectrum of diseases is promising, such as spinal cord injury, cardiovascular repair, bone and cartilage repair. The current review also discusses the issues of using of allogeneic MSCs for clinical therapy.

  10. Successful autologous stem cell collection with filgrastim and plerixafor after long-term lenalidomide therapy for multiple myeloma

    Directory of Open Access Journals (Sweden)

    Rishi Agarwal

    2012-12-01

    Full Text Available Novel agents such as lenalidomide have demonstrated responses similar to high-dose melphalan and autologous stem cell transplant in multiple myeloma. For patients who are started on lenalidomide, it is advisable to collect stem cells early if future transplant is contemplated. We are reporting a patient who underwent successful stem cell mobilization after 68 cycles of lenalidomide. A 60-year old male presented with back pain. He was diagnosed with stage IIA, IgA multiple myeloma. He was enrolled in a clinical trial and was randomized to receive lenalidomide plus dexamethasone. He received a total of 68 cycles of lenalidomide before progressing. He underwent mobilization of stem cells using filgrastim and plerixafor. He underwent successful stem cell transplant. Longer duration of lenalidomide adversely effects stem cell mobilization. To the best of our knowledge, there has been no other case reported in which stem cell mobilization was feasible after such a long (68 months duration of uninterrupted lenalidomide therapy.

  11. Patterns of amino acid metabolism by proliferating human mesenchymal stem cells

    NARCIS (Netherlands)

    Higuera, G.A.; Schop, D.; Spitters, T.W.; Dijkhuizen, R.; Bracke, M.; Bruijn, J.D.; Martens, D.E.; Karperien, M.; Boxtel, van A.J.B.; Blitterswijk, van C.A.

    2012-01-01

    The nutritional requirements of stem cells have not been determined; in particular, the amino acid metabolism of stem cells is largely unknown. In this study, we investigated the amino acid metabolism of human mesenchymal stem cells (hMSCs), with focus on two questions: Which amino acids are consume

  12. Are Sertoli cells a kind of mesenchymal stem cells?

    Science.gov (United States)

    Gong, Daoyuan; Zhang, Chunfu; Li, Tao; Zhang, Jiahui; Zhang, Nannan; Tao, Zehua; Zhu, Wei; Sun, Xiaochun

    2017-01-01

    Objective: Sertoli cells (SCs) are a major component of testis which secrete a variety of cytokines and immunosuppressive factors, providing nutritional support and immune protection for sperm growth and development. The purpose of this study was to investigate the relationship between SCs and bone marrow mesenchymal stem cells (BMSCs) in order to provide a theoretical basis for better application of SCs. Methods: We used the adherence method to isolate Sprague-Dawley rat SCs and BMSCs. Cells surface markers were detected by flow cytometry. The capacity of cells to differentiate was determined by osteogenic and adipogenic induction. Assessment of cell proliferation was performed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2-H-tetrazolium bromide] assay. Changes in the nucleus were analyzed by Hoechst nuclear staining. Cell aging was observed with β-galactosidase, which is a biological marker of senescence. RT-PCR was employed to detect the expression of cytokines. Results: From the aforementioned experiments, we found that the surface markers of SCs and BMSCs were almost exactly the same. Proliferation of SCs, as well as osteogenic and adipogenic differentiation, were weaker than in BMSCs. Compared with BMSCs, Hoechst nuclear staining showed that the chromatin of SCs began to aggregate and was slightly larger. β-galactosidase staining showed that SCs were in a slightly aging state. The secretion of cytokines from SCs was slightly less than the secretion from BMSCs. Conclusion: SCs are a kind of mesenchymal stem cells which have begun the process of differentiation. PMID:28386334

  13. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells

    OpenAIRE

    Mari Dezawa; Taeko Shigemoto; Fumitaka Ogura; Shohei Wakao; Yasumasa Kuroda

    2012-01-01

    Mesenchymal stem cells (MSCs) are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have no...

  14. Myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory T cells

    Directory of Open Access Journals (Sweden)

    Sunyoung Joo

    2014-02-01

    Full Text Available Cell therapy for patients who have intractable muscle disorders may require highly regenerative cells from young, healthy allogeneic donors. Mesenchymal stem cells are currently under clinical investigation because they are known to induce muscle regeneration and believed to be immune privileged, thus making them suitable for allogeneic applications. However, it is unclear whether allogeneic and myogenic-induced mesenchymal stem cells retain their immunomodulatory characteristics. Therefore, our aim was to evaluate the effects of mesenchymal stem cell differentiation on the immune characteristics of cells in vitro. We investigated the immunologic properties of mesenchymal stem cells after myogenic induction. Mesenchymal stem cells were obtained from C57BL/6 mice and the C3H/10T1/2 murine mesenchymal stem cell line. Two different 5-aza-2′-deoxycytidine doses (0.5 and 3 µM were evaluated for their effects on mesenchymal stem cell skeletal myogenic differentiation potential, immune antigen expression, and mixed lymphocytic reactions. Using a mixed lymphocytic reaction, we determined the optimal splenocyte proliferation inhibition dose. The induction of regulatory T cells was markedly increased by the addition of 3 µM 5-aza-2′-deoxycytidine–treated mesenchymal stem cells. Myogenic-induced mesenchymal stem cells do not elicit alloreactive lymphocyte proliferative responses and are able to modulate immune responses. These findings support the hypothesis that myogenic-induced mesenchymal stem cells may be transplantable across allogeneic barriers.

  15. Genetic Engineering of Mesenchymal Stem Cells and Its Application in Human Disease Therapy

    OpenAIRE

    Hodgkinson, Conrad P; Gomez, José A.; Mirotsou, Maria; Dzau, Victor J.

    2010-01-01

    Hodgkinson and colleagues review the current status of knowledge with respect to the genetic modifications being explored as a means to improve mesenchymal stem cell therapy for human diseases, with a particular focus on cardiovascular diseases.

  16. Acetylcholine secretion by motor neuron-like cells from umbilical cord mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Xueyuan Liu; Dehua Li; Dong Jiang; Yan Fang

    2013-01-01

    Umbilical cord mesenchymal stem cel s were isolated by a double enzyme digestion method. The third passage of umbilical cord mesenchymal stem cel s was induced with heparin and/or basic fi-broblast growth factor. Results confirmed that cel morphology did not change after induction with basic fibroblast growth factor alone. However, neuronal morphology was visible, and microtu-bule-associated protein-2 expression and acetylcholine levels increased fol owing induction with heparin alone or heparin combined with basic fibroblast growth factor. Hb9 and choline acetyl-transferase expression was high fol owing inductive with heparin combined with basic fibroblast growth factor. Results indicate that the inductive effect of basic fibroblast growth factor alone was not obvious. Heparin combined with basic fibroblast growth factor noticeably promoted the differen-tiation of umbilical cord mesenchymal stem cel s into motor neuron-like cel s. Simultaneously, um-bilical cord mesenchymal stem cel s could secrete acetylcholine.

  17. Citalopram increases the differentiation efifcacy of bone marrow mesenchymal stem cells into neuronal-like cells

    Institute of Scientific and Technical Information of China (English)

    Javad Verdi; Seyed Abdolreza Mortazavi-Tabatabaei; Shiva Sharif; Hadi Verdi; Alireza Shoae-Hassani

    2014-01-01

    Several studies have demonstrated that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. It is hypothesized that citalopram, a selective serotonin reuptake inhibitor, can promote the neuronal differentiation of adult bone marrow mesenchymal stem cells. Citalopram strongly enhanced neuronal characteristics of the cells derived from bone marrow mesenchymal stem cells. The rate of cell death was decreased in citalopram-treated bone marrow mesenchymal stem cells than in control cells in neurobasal medium. In addition, the cumulative population doubling level of the citalopram-treated cells was signiifcantly increased compared to that of control cells. Also BrdU incorporation was elevated in citalopram-treated cells. These ifndings suggest that citalopram can improve the neuronal-like cell differentiation of bone marrow mesenchymal stem cells by increasing cell proliferation and survival while maintaining their neuronal characteristics.

  18. Tumour-Derived Interleukin-1 Beta Induces Pro-inflammatory Response in Human Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Alajez, Nehad M; Al-toub, Mashael; Almusa, Abdulaziz

    Problem Studying cancer tumors microenvironment may reveal a novel role in driving cancer progression and metastasis. The biological interaction between stromal (mesenchymal) stem cells (MSCs) and cancer cells remains incompletely understood. Herein, we investigated the effects of tumor cells’ se...

  19. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Fatemeh Anbari; Mohammad Ali Khalili; Ahmad Reza Bahrami; Arezoo Khoradmehr; Fatemeh Sadeghian; Farzaneh Fesahat; Ali Nabi

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intrave-nous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and ad-ministered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significant-ly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells.

  20. Evaluation of Proliferation and Development of Mesenchymal Stem Cell on Nanoporous PLLA Membrane Scaffold

    Directory of Open Access Journals (Sweden)

    MH Porghara

    2015-08-01

    Conclusion: Due to the biodegradable and non-toxic properties of nano PLLA membrane, it could increase the adhesion and proliferation of mesenchymal stem cells and these effects will exacerbated over time.

  1. Imaging gene expression in human mesenchymal stem cells: from small to large animals

    DEFF Research Database (Denmark)

    Willmann, Jürgen K; Paulmurugan, Ramasamy; Rodriguez-Porcel, Martin;

    2009-01-01

    To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning....

  2. 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

  3. The paracrine effect of mesenchymal human stem cells restored hearing in β-tubulin induced autoimmune sensorineural hearing loss.

    Science.gov (United States)

    Yoo, T J; Du, Xiaoping; Zhou, Bin

    2015-12-01

    The aim of this study was to examine the activities of hASCs (Human Adipose tissue Derived Stem Cells) on experimental autoimmune hearing loss (EAHL) and how human stem cells regenerated mouse cochlea cells. We have restored hearing in 19 years old white female with autoimmune hearing loss with autologous adipose tissue derived stem cells and we wish to understand the mechanism of restoration of hearing in animal model. BALB/c mice underwent to develop EAHL; mice with EAHL were given hASCs intraperitoneally once a week for 6 consecutive weeks. ABR were examined over time. The helper type 1 autoreactive responses and T-reg cells were examined. H&E staining or immunostaining with APC conjugated anti-HLA-ABC antibody were conducted. The organ of Corti, stria vascularis, spira ligament and spiral ganglion in stem cell group are normal. In control group, without receiving stem cells, the organ of Corti is replaced by a single layer of cells, atrophy of stria vascularis. Systemic infusion of hASCs significantly improved hearing function and protected hair cells in established EAHL. The hASCs decreased the proliferation of antigen specific Th1/Th17 cells and induced the production of anti-inflammatory cytokine interleukin10 in splenocytes. They also induced the generation of antigen specific CD4(+)CD25(+)Foxp3(+)T-reg cells. The experiment showed the restoration is due to the paracrine activities of human stem cells, since there are newly regenerated mice spiral ganglion cells, not human mesenchymal stem cells derived tissue given by intraperitoneally.

  4. An animal model of peripheral nerve regeneration after the application of a collagen-polyvinyl alcohol scaffold and mesenchymal stem cells.

    Science.gov (United States)

    Marinescu, Silviu Adrian; Zărnescu, Otilia; Mihai, Ioana Ruxandra; Giuglea, Carmen; Sinescu, Ruxandra Diana

    2014-01-01

    Extensive nerve injuries often leading to nerve gaps can benefit, besides the gold standard represented by autologous nerve grafts, by the inciting field of tissue engineering. To enhance the role of biomaterials in nerve regeneration, the nerve conduits are associated with Schwann or Schwann-like cells. In this study, we evaluated rat sciatic nerve regeneration, by using a biodegradable nerve guide composed of Collagen (COL) and Polyvinyl Alcohol (PVA), associated with mesenchymal stem cells (MSC). After the exposure of the rat sciatic nerve, a nerve gap was created by excising 1 cm of the nerve. Three experimental groups were used for nerve gap bridging: autografts, nerve conduits filled with medium culture and nerve conduits filled with MSC. The methods of sensory and motor assessment consisted of the functional evaluation of sciatic nerve recovery - toe-spread, pinprick tests and gastrocnemius muscle index (GMI). The histological and immunocytochemical analysis of the probes that were harvested from the repair site was performed at 12 weeks. Successful nerve regeneration was noted in all three groups at the end of the 12th week. The functional and immunocytochemical results suggested that COL-PVA tubes supported with mesenchymal stem cells could be considered similar to autologous nerve grafts in peripheral nerve regeneration, without the drawbacks of the last ones. The functional results were better for the autografts and the ultrastructural data were better for the nerve conduits, but there were not noticed any statistical differences.

  5. The Role of Mesenchymal Stem Cells in Promoting Ovarian Cancer Growth and Spread

    Science.gov (United States)

    2014-12-01

    home to tissue injury. Monocyte polarization into the classically activated pro- inflam - matory macrophages (M1) occurs early on in tissue repair, whereas...AWARD NUMBER: W81XWH-12-1-0438 TITLE: The Role of Mesenchymal Stem Cells in Promoting Ovarian Cancer Growth and Spread PRINCIPAL INVESTIGATOR...SUBTITLE The Role of Mesenchymal Stem Cells in Promoting Ovarian Cancer Growth and Spread 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0438 5c

  6. Human amnion mesenchymal stem cells promote proliferation and osteogenic differentiation in human bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Wang, Yuli; Yin, Ying; Jiang, Fei; Chen, Ning

    2015-02-01

    Human amnion mesenchymal stem cells (HAMSCs) can be obtained from human amniotic membrane, a highly abundant and readily available tissue. HAMSC sources present fewer ethical issues, have low immunogenicity, anti-inflammatory properties, considerable advantageous characteristics, and are considered an attractive potential treatment material in the field of regenerative medicine. We used a co-culture system to determine whether HAMSCs could promote osteogenesis in human bone marrow mesenchymal stem cells (HBMSCs). We isolated HAMSCs from discarded amnion samples and collected them using pancreatin/collagenase digestion. We cultured HAMSCs and HBMSCSs in basal medium. Activity of alkaline phosphatase (ALP), an early osteogenesis marker, was increased in the co-culture system compared to the control single cultures, which we also confirmed by ALP staining. We used immunofluorescence testing to investigate the effects of co-culturing with HAMSCs on HBMSC proliferation, which revealed that the co-culturing enhanced EdU expression in HBMSCs. Western blotting and quantitative real-time PCR indicated that co-culturing promoted osteogenesis in HBMSCs. Furthermore, Alizarin red S staining revealed that extracellular matrix calcium levels in mineralized nodule formation produced by the co-cultures were higher than that in the controls. Using the same co-culture system, we further observed the effects of HAMSCs on osteogenic differentiation in primary osteoblasts by Western blotting, which better addressed the mechanism for HAMSCs in bone regeneration. The results showed HAMSCs are osteogenic and not only play a role in promoting HBMSC proliferation and osteogenic differentiation but also in osteoblasts, laying the foundation for new regenerative medicine methods.

  7. Eccentric exercise facilitates mesenchymal stem cell appearance in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    M Carmen Valero

    Full Text Available Eccentric, or lengthening, contractions result in injury and subsequently stimulate the activation and proliferation of satellite stem cells which are important for skeletal muscle regeneration. The discovery of alternative myogenic progenitors in skeletal muscle raises the question as to whether stem cells other than satellite cells accumulate in muscle in response to exercise and contribute to post-exercise repair and/or growth. In this study, stem cell antigen-1 (Sca-1 positive, non-hematopoetic (CD45⁻ cells were evaluated in wild type (WT and α7 integrin transgenic (α7Tg mouse muscle, which is resistant to injury yet liable to strain, 24 hr following a single bout of eccentric exercise. Sca-1⁺CD45⁻ stem cells were increased 2-fold in WT muscle post-exercise. The α7 integrin regulated the presence of Sca-1⁺ cells, with expansion occurring in α7Tg muscle and minimal cells present in muscle lacking the α7 integrin. Sca-1⁺CD45⁻ cells isolated from α7Tg muscle following exercise were characterized as mesenchymal-like stem cells (mMSCs, predominantly pericytes. In vitro multiaxial strain upregulated mMSC stem cells markers in the presence of laminin, but not gelatin, identifying a potential mechanistic basis for the accumulation of these cells in muscle following exercise. Transplantation of DiI-labeled mMSCs into WT muscle increased Pax7⁺ cells and facilitated formation of eMHC⁺DiI⁻ fibers. This study provides the first demonstration that mMSCs rapidly appear in skeletal muscle in an α7 integrin dependent manner post-exercise, revealing an early event that may be necessary for effective repair and/or growth following exercise. The results from this study also support a role for the α7 integrin and/or mMSCs in molecular- and cellular-based therapeutic strategies that can effectively combat disuse muscle atrophy.

  8. Clinical Applications of Mesenchymal Stem Cells in Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Andrea Farini

    2014-01-01

    Full Text Available Extraordinary progress in understanding several key features of stem cells has been made in the last ten years, including definition of the niche, and identification of signals regulating mobilization and homing as well as partial understanding of the mechanisms controlling self-renewal, commitment, and differentiation. This progress produced invaluable tools for the development of rational cell therapy protocols that have yielded positive results in preclinical models of genetic and acquired diseases and, in several cases, have entered clinical experimentation with positive outcome. Adult mesenchymal stem cells (MSCs are nonhematopoietic cells with multilineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. It is obvious that much work remains to be done to increase our knowledge of the mechanisms regulating development, homeostasis, and tissue repair and thus to provide new tools to implement the efficacy of cell therapy trials.

  9. Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine.

    Science.gov (United States)

    Nowakowski, Adam; Walczak, Piotr; Janowski, Miroslaw; Lukomska, Barbara

    2015-10-01

    Mesenchymal stem cells (MSCs), which can be obtained from various organs and easily propagated in vitro, are one of the most extensively used types of stem cells and have been shown to be efficacious in a broad set of diseases. The unique and highly desirable properties of MSCs include high migratory capacities toward injured areas, immunomodulatory features, and the natural ability to differentiate into connective tissue phenotypes. These phenotypes include bone and cartilage, and these properties predispose MSCs to be therapeutically useful. In addition, MSCs elicit their therapeutic effects by paracrine actions, in which the metabolism of target tissues is modulated. Genetic engineering methods can greatly amplify these properties and broaden the therapeutic capabilities of MSCs, including transdifferentiation toward diverse cell lineages. However, cell engineering can also affect safety and increase the cost of therapy based on MSCs; thus, the advantages and disadvantages of these procedures should be discussed. In this review, the latest applications of genetic engineering methods for MSCs with regenerative medicine purposes are presented.

  10. Proteomic Applications in the Study of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Jesús Mateos

    2014-02-01

    Full Text Available Mesenchymal stem cells (MSCs are undifferentiated cells with an unlimited capacity for self-renewal and able to differentiate towards specific lineages under appropriate conditions. MSCs are, a priori, a good target for cell therapy and clinical trials as an alternative to embryonic stem cells, avoiding ethical problems and the chance for malignant transformation in the host. However, regarding MSCs, several biological implications must be solved before their application in cell therapy, such as safe ex vivo expansion and manipulation to obtain an extensive cell quantity amplification number for use in the host without risk accumulation of genetic and epigenetic abnormalities. Cell surface markers for direct characterization of MSCs remain unknown, and the precise molecular mechanisms whereby growth factors stimulate their differentiation are still missing. In the last decade, quantitative proteomics has emerged as a promising set of techniques to address these questions, the answers to which will determine whether MSCs retain their potential for use in cell therapy. Proteomics provides tools to globally analyze cellular activity at the protein level. This proteomic profiling allows the elucidation of connections between broad cellular pathways and molecules that were previously impossible to determine using only traditional biochemical analysis. However; thus far, the results obtained must be orthogonally validated with other approaches. This review will focus on how these techniques have been applied in the evaluation of MSCs for their future applications in safe therapies.

  11. Proteomic Applications in the Study of Human Mesenchymal Stem Cells

    Science.gov (United States)

    Mateos, Jesús; Fernández Pernas, Pablo; Fafián Labora, Juan; Blanco, Francisco; Arufe, María del Carmen

    2014-01-01

    Mesenchymal stem cells (MSCs) are undifferentiated cells with an unlimited capacity for self-renewal and able to differentiate towards specific lineages under appropriate conditions. MSCs are, a priori, a good target for cell therapy and clinical trials as an alternative to embryonic stem cells, avoiding ethical problems and the chance for malignant transformation in the host. However, regarding MSCs, several biological implications must be solved before their application in cell therapy, such as safe ex vivo expansion and manipulation to obtain an extensive cell quantity amplification number for use in the host without risk accumulation of genetic and epigenetic abnormalities. Cell surface markers for direct characterization of MSCs remain unknown, and the precise molecular mechanisms whereby growth factors stimulate their differentiation are still missing. In the last decade, quantitative proteomics has emerged as a promising set of techniques to address these questions, the answers to which will determine whether MSCs retain their potential for use in cell therapy. Proteomics provides tools to globally analyze cellular activity at the protein level. This proteomic profiling allows the elucidation of connections between broad cellular pathways and molecules that were previously impossible to determine using only traditional biochemical analysis. However; thus far, the results obtained must be orthogonally validated with other approaches. This review will focus on how these techniques have been applied in the evaluation of MSCs for their future applications in safe therapies.

  12. Impairment of mesenchymal stem cells derived from oral leukoplakia.

    Science.gov (United States)

    Zhang, Zhihui; Song, Jiangyuan; Han, Ying; Mu, Dongdong; Su, Sha; Ji, Xiaoli; Liu, Hongwei

    2015-01-01

    Oral leukoplakia is one of the common precancerous lesions in oral mucosa. To compare the biological characteristics and regenerative capacities of mesenchymal stem cells (MSCs) from oral leukoplakia (epithelial hyperplasia and dysplasia) and normal oral mucosa, MSCs were isolated by enzyme digestion. Then these cells were identified by the expression of MSC related markers, STRO-1, CD105 and CD90, with the absent for the hematopoietic stem cell marker CD34 by flow cytometric detection. The self-renewal ability of MSCs from oral leukoplakia was enhanced, while the multipotent differentiation was descended, compared with MSCs from normal oral mucosa. Fibrin gel was used as a carrier for MSCs transplanted into immunocompromised mice to detect their regenerative capacity. The regenerative capacities of MSCs from oral leukoplakia became impaired partly. Collagen IV (Col IV) and matrix metalloproteinases-9 (MMP-9) were selected to analyze the potential mechanism for the functional changes of MSCs from oral leukoplakia by immunochemical and western blot analysis. The expression of Col IV was decreased and that of MMP-9 was increased by MSCs with the progression of oral leukoplakia, especially in MSCs from epithelial dysplasia. The imbalance between regenerative and metabolic self-regulatory functions of MSCs from oral leukoplakia may be related to the progression of this premalignant disorder.

  13. Geometric cues for directing the differentiation of mesenchymal stem cells

    Science.gov (United States)

    Kilian, Kristopher A.; Bugarija, Branimir; Lahn, Bruce T.; Mrksich, Milan

    2010-01-01

    Significant efforts have been directed to understanding the factors that influence the lineage commitment of stem cells. This paper demonstrates that cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow. When exposed to competing soluble differentiation signals, cells cultured in rectangles with increasing aspect ratio and in shapes with pentagonal symmetry but with different subcellular curvature—and with each occupying the same area—display different adipogenesis and osteogenesis profiles. The results reveal that geometric features that increase actomyosin contractility promote osteogenesis and are consistent with in vivo characteristics of the microenvironment of the differentiated cells. Cytoskeletal-disrupting pharmacological agents modulate shape-based trends in lineage commitment verifying the critical role of focal adhesion and myosin-generated contractility during differentiation. Microarray analysis and pathway inhibition studies suggest that contractile cells promote osteogenesis by enhancing c-Jun N-terminal kinase (JNK) and extracellular related kinase (ERK1/2) activation in conjunction with elevated wingless-type (Wnt) signaling. Taken together, this work points to the role that geometric shape cues can play in orchestrating the mechanochemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates. PMID:20194780

  14. Mesenchymal stromal cells and hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bernardo, Maria Ester; Fibbe, Willem E

    2015-12-01

    Mesenchymal stromal cells (MSCs) comprise a heterogeneous population of multipotent cells that can be isolated from various human tissues and culture-expanded ex vivo for clinical use. Due to their immunoregulatory properties and their ability to secrete growth factors, MSCs play a key role in the regulation of hematopoiesis and in the modulation of immune responses against allo- and autoantigens. In light of these properties, MSCs have been employed in clinical trials in the context of hematopoietic stem cell transplantation (HSCT) to facilitate engraftment of hematopoietic stem cells (HSCs) and to prevent graft failure, as well as to treat steroid-resistant acute graft-versus-host disease (GvHD). The available clinical evidence derived from these studies indicates that MSC administration is safe. Moreover, promising preliminary results in terms of efficacy have been reported in some clinical trials, especially in the treatment of acute GvHD. In this review we critically discuss recent advances in MSC therapy by reporting on the most relevant studies in the field of HSCT.

  15. Mesenchymal stem cell therapy for osteoarthritis: current perspectives.

    Science.gov (United States)

    Wyles, Cody C; Houdek, Matthew T; Behfar, Atta; Sierra, Rafael J

    2015-01-01

    Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs) are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.

  16. Mesenchymal stem cells support hepatocyte function in engineered liver grafts.

    Science.gov (United States)

    Kadota, Yoshie; Yagi, Hiroshi; Inomata, Kenta; Matsubara, Kentaro; Hibi, Taizo; Abe, Yuta; Kitago, Minoru; Shinoda, Masahiro; Obara, Hideaki; Itano, Osamu; Kitagawa, Yuko

    2014-01-01

    Recent studies suggest that organ decellularization is a promising approach to facilitate the clinical application of regenerative therapy by providing a platform for organ engineering. This unique strategy uses native matrices to act as a reservoir for the functional cells which may show therapeutic potential when implanted into the body. Appropriate cell sources for artificial livers have been debated for some time. The desired cell type in artificial livers is primary hepatocytes, but in addition, other supportive cells may facilitate this stem cell technology. In this context, the use of mesenchymal stem cells (MSC) is an option meeting the criteria for therapeutic organ engineering. Ideally, supportive cells are required to (1) reduce the hepatic cell mass needed in an engineered liver by enhancing hepatocyte function, (2) modulate hepatic regeneration in a paracrine fashion or by direct contact, and (3) enhance the preservability of parenchymal cells during storage. Here, we describe enhanced hepatic function achieved using a strategy of sequential infusion of cells and illustrate the advantages of co-cultivating bone marrow-derived MSCs with primary hepatocytes in the engineered whole-liver scaffold. These co-recellularized liver scaffolds colonized by MSCs and hepatocytes were transplanted into live animals. After blood flow was established, we show that expression of adhesion molecules and proangiogenic factors was upregulated in the graft.

  17. Mesenchymal Stem Cells Derived from Dental Pulp: A Review

    Directory of Open Access Journals (Sweden)

    Edgar Ledesma-Martínez

    2016-01-01

    Full Text Available The mesenchymal stem cells of dental pulp (DPSCs were isolated and characterized for the first time more than a decade ago as highly clonogenic cells that were able to generate densely calcified colonies. Now, DPSCs are considered to have potential as stem cell source for orthopedic and oral maxillofacial reconstruction, and it has been suggested that they may have applications beyond the scope of the stomatognathic system. To date, most studies have shown that, regardless of their origin in third molars, incisors, or exfoliated deciduous teeth, DPSCs can generate mineralized tissue, an extracellular matrix and structures type dentin, periodontal ligament, and dental pulp, as well as other structures. Different groups worldwide have designed and evaluated new efficient protocols for the isolation, expansion, and maintenance of clinically safe human DPSCs in sufficient numbers for various therapeutics protocols and have discussed the most appropriate route of administration, the possible contraindications to their clinical use, and the parameters to be considered for monitoring their clinical efficacy and proper biological source. At present, DPSC-based therapy is promising but because most of the available evidence was obtained using nonhuman xenotransplants, it is not a mature technology.

  18. Cardiac differentiation and electrophysiology characteristics of bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    LIU Bo-wu; AI Shi-yi; L(U) An-lin; HOU Jing; HUANG Wei; LI Yao; HOU Zhao-lei; HOU Hong; DA Jing; YANG Na

    2012-01-01

    Objective To review the progress of cardiac differentiation and electrophysiological characteristics of bone marrow mesenchymal stem cells.Data sources The databases of PubMed,Springer Link,Science Direct and CNKI were retrieved for papers published from January 2000 to January 2012 with the key words of “bone marrow mesenchymal stem cells,cardiac or heart,electrophysiology or electrophysiological characteristics”.Study selection The articles concerned cardiac differentiation and electrophysiological characteristics of bone marrow mesenchymal stem cells were collected.After excluding papers that study purposes are not coincident with this review or contents duplicated,56 papers were internalized at last.Results For the treatment of myocardial infarction and myocardiac disease,the therapeutic effects of transplantation of bone marrow mesenchymal stem cells which have the ability to develop into functional myocardial cells by lots of methods have been proved by many researches.But the arrhythmogenic effect on ventricles affer transplantation of bone marrow mesenchymal stem cells derived myocardial cells is still controversial in animal models.Certainly,the low differentiation efficiency and heterogeneous development of electricial function could be the most important risk for proarrhythmia.Conclusion Many studies of cardiac differentiation of bone marrow mesenchymal stem cells have paid attention to improve the cardiac differentiation rate,and the electrophysiology characteristics of the differentiated cells should be concerned for the risk for proarrhythmia as well.

  19. Mesenchymal Stem Cell Therapy for the Treatment of Vocal Fold Scarring

    DEFF Research Database (Denmark)

    Wingstrand, Vibe Lindeblad; Grønhøj Larsen, Christian; Jensen, David H;

    2016-01-01

    OBJECTIVES: Therapy with mesenchymal stem cells exhibits potential for the development of novel interventions for many diseases and injuries. The use of mesenchymal stem cells in regenerative therapy for vocal fold scarring exhibited promising results to reduce stiffness and enhance the biomechan......OBJECTIVES: Therapy with mesenchymal stem cells exhibits potential for the development of novel interventions for many diseases and injuries. The use of mesenchymal stem cells in regenerative therapy for vocal fold scarring exhibited promising results to reduce stiffness and enhance...... the biomechanical properties of injured vocal folds. This study evaluated the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring. DATA SOURCES: PubMed, Embase, the Cochrane Library and Google Scholar were searched. METHODS: Controlled studies that assessed...... the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring were included. Primary outcomes were viscoelastic properties and mucosal wave amplitude. RESULTS: Seven preclinical animal studies (n = 152 single vocal folds) were eligible for inclusion. Evaluation of viscoelastic...

  20. The hematopoietic growth factor "erythropoietin" enhances the therapeutic effect of mesenchymal stem cells in Alzheimer's disease.

    Science.gov (United States)

    Khairallah, M I; Kassem, L A; Yassin, N A; El Din, M A Gamal; Zekri, M; Attia, M

    2014-01-01

    Alzheimer's disease is a neurodegenerative disorder clinically characterized by cognitive dysfunction and by deposition of amyloid plaques, neurofibrillary tangles in the brain. The study investigated the therapeutic effect of combined mesenchymal stem cells and erythropoietin on Alzheimer's disease. Five groups of mice were used: control group, Alzheimer's disease was induced in four groups by a single intraperitoneal injection of 0.8 mg kg(-1) lipopolysaccharide and divided as follows: Alzheimer's disease group, mesenchymal stem cells treated group by injecting mesenchymal stem cells into the tail vein (2 x 10(6) cells), erythropoietin treated group (40 microg kg(-1) b.wt.) injected intraperitoneally 3 times/week for 5 weeks and mesenchymal stem cells and erythropoietin treated group. Locomotor activity and memory were tested using open field and Y-maze. Histological, histochemical, immunohistochemical studies, morphometric measurements were examined in brain sections of all groups. Choline transferase activity, brain derived neurotrophic factor expression and mitochondrial swellings were assessed in cerebral specimens. Lipopolysaccharide decreased locomotor activity, memory, choline transferase activity and brain derived neurotrophic factor. It increased mitochondrial swelling, apoptotic index and amyloid deposition. Combined mesenchymal stem cells and erythropoietin markedly improved all these parameters. This study proved the effective role of mesenchymal stem cells in relieving Alzheimer's disease symptoms and manifestations; it highlighted the important role of erythropoietin in the treatment of Alzheimer's disease.

  1. Use of FK506 and bone marrow mesenchymal stem cells for rat hind limb allografts

    Institute of Scientific and Technical Information of China (English)

    Youxin Song; Zhujun Wang; Zhixue Wang; Hong Zhang; Xiaohui Li; Bin Chen

    2012-01-01

    Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplanted limbs in the microenvironment of immunotolerance. bone marrow mesenchymal stem cells were intramuscularly (gluteus maximus) injected with FK506 (tacrolimus) daily, and were transplanted to the injured nerves. Results indicated that the allograft group not receiving therapy showed severe rejection, with transplanted limbs detaching at 10 days after transplantation with complete necrosis. The number of myelinated axons and Schwann cells in the FK506 and FK506 + bone marrow mesenchymal stem cells groups were significantly increased. We observed a lesser degree of gastrocnemius muscle degeneration, and increased polymorphic fibers along with other pathological changes in the FK506 + bone marrow mesenchymal stem cells group. The FK506 + bone marrow mesenchymal stem cells group showed significantly better recovery than the autograft and FK506 groups. The results demonstrated that FK506 improved the immune microenvironment. FK506 combined with bone marrow mesenchymal stem cells significantly promoted sciatic nerve regeneration, and improved sensory recovery and motor function in hind limb allotransplant.

  2. Autologous peripheral blood stem cell transplantation in patients with relapsed lymphoma results in accelerated haematopoietic reconstitution, improved quality of life and cost reduction compared with bone marrow transplantation : the Hovon 22 study

    NARCIS (Netherlands)

    Vellenga, E; van Agthoven, M; Croockewit, AJ; Verdonck, LF; Wijermans, PJ; van Oers, MHJ; Volkers, CP; van Imhoff, GW; Kingma, T; Uyl-de Groot, CA; Fibbe, WE

    2001-01-01

    The present study analysed whether autologous peripheral blood stem cell transplantation (PSCT) improves engraftment, quality of life and cost-effectiveness when compared with autologous bone marrow transplantation (ABMT). Relapsing progressive lymphoma patients (n = 204; non-Hodgkin's lymphoma n =

  3. Clinical outcomes after autologous haematopoietic stem cell transplantation in patients with progressive multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    XU Juan; JI Bing-xin; SU Li; DONG Hui-qing; SUN Xue-jing; LIU Cong-yan

    2006-01-01

    Background Multiple sclerosis (MS) is a continuously disabling disease and it is unresponsive to high dose steroid and immunomodulation with disease progression. The autologous haematopoietic stem cell transplantation (ASCT) has been introduced in the treatment of refractory forms of multiple sclerosis. In this study, the clinical outcomes followed by ASCT were evaluated for patients with progressive MS.Methods Twenty-two patients with secondary progressive MS were treated with ASCT. Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony stimulating factor. Etoposide,melphalan, carmustin and cytosine arabinoside were administered as conditioning regimen. Outcomes were evaluated by the expanded disability status scale and progression free survival. No maintenance treatment was administered during a median follow-up of 39 months (range, 6 to 59 months).Results No death occurred following the treatment. The overall confirmed progression free survival rate was77% up to 59 months after transplantation which was significantly higher compared with pre-transplantation (P=0.000). Thirteen patients (59%) had remarkable improvement in neurological manifestations, four (18%)stabilized their disability status and five (23%) showed clinical recurrence of active symptoms.Conclusions ASCT as a therapy is safe and available. It can improve or stabilize neurological manifestations in most patients with progressive MS following failure of conventional therapy.

  4. Clinical significance of abnormal protein bands in multiple myeloma treated with bortezmib-based induction regimen and autologous stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    王荷花

    2013-01-01

    Objective To study the clinical significance of abnormal protein bands(APB)in multiple myeloma(MM) patients treated with bortezomib-based induction regimen and autologous stem cell transplantation(ASCT)

  5. Observation of humoral immunity reconstitution and its relationship with infection after autologous hematopoietic stem cell transplantation for patients with multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    刘俊茹

    2013-01-01

    Objective To study the humoral immunity reconstitution and its relationship with infection in patients with multiple myeloma(MM) after undergoing autologous hematopoietic stem cell transplantation(auto-HSCT)

  6. The endometrium as a source of mesenchymal stem cells for regenerative medicine.

    Science.gov (United States)

    Mutlu, Levent; Hufnagel, Demetra; Taylor, Hugh S

    2015-06-01

    Stem cell therapies have opened new frontiers in medicine with the possibility of regenerating lost or damaged cells. Embryonic stem cells, induced pluripotent stem cells, hematopoietic stem cells, and mesenchymal stem cells have been used to derive mature cell types for tissue regeneration and repair. However, the endometrium has emerged as an attractive, novel source of adult stem cells that are easily accessed and demonstrate remarkable differentiation capacity. In this review, we summarize our current understanding of endometrial stem cells and their therapeutic potential in regenerative medicine.

  7. Clinical Trials With Mesenchymal Stem Cells: An Update.

    Science.gov (United States)

    Squillaro, Tiziana; Peluso, Gianfranco; Galderisi, Umberto

    2016-01-01

    In the last year, the promising features of mesenchymal stem cells (MSCs), including their regenerative properties and ability to differentiate into diverse cell lineages, have generated great interest among researchers whose work has offered intriguing perspectives on cell-based therapies for various diseases. Currently the most commonly used adult stem cells in regenerative medicine, MSCs, can be isolated from several tissues, exhibit a strong capacity for replication in vitro, and can differentiate into osteoblasts, chondrocytes, and adipocytes. However, heterogeneous procedures for isolating and cultivating MSCs among laboratories have prompted the International Society for Cellular Therapy (ISCT) to issue criteria for identifying unique populations of these cells. Consequently, the isolation of MSCs according to ISCT criteria has produced heterogeneous, nonclonal cultures of stromal cells containing stem cells with different multipotent properties, committed progenitors, and differentiated cells. Though the nature and functions of MSCs remain unclear, nonclonal stromal cultures obtained from bone marrow and other tissues currently serve as sources of putative MSCs for therapeutic purposes, and several findings underscore their effectiveness in treating different diseases. To date, 493 MSC-based clinical trials, either complete or ongoing, appear in the database of the US National Institutes of Health. In the present article, we provide a comprehensive review of MSC-based clinical trials conducted worldwide that scrutinizes biological properties of MSCs, elucidates recent clinical findings and clinical trial phases of investigation, highlights therapeutic effects of MSCs, and identifies principal criticisms of the use of these cells. In particular, we analyze clinical trials using MSCs for representative diseases, including hematological disease, graft-versus-host disease, organ transplantation, diabetes, inflammatory diseases, and diseases in the liver, kidney

  8. Glial cell derived neurotrophic factor induces spermatogonial stem cell marker genes in chicken mesenchymal stem cells.

    Science.gov (United States)

    Boozarpour, Sohrab; Matin, Maryam M; Momeni-Moghaddam, Madjid; Dehghani, Hesam; Mahdavi-Shahri, Naser; Sisakhtnezhad, Sajjad; Heirani-Tabasi, Asieh; Irfan-Maqsood, Muhammad; Bahrami, Ahmad Reza

    2016-06-01

    Mesenchymal stem cells (MSCs) are known with the potential of multi-lineage differentiation. Advances in differentiation technology have also resulted in the conversion of MSCs to other kinds of stem cells. MSCs are considered as a suitable source of cells for biotechnology purposes because they are abundant, easily accessible and well characterized cells. Nowadays small molecules are introduced as novel and efficient factors to differentiate stem cells. In this work, we examined the potential of glial cell derived neurotrophic factor (GDNF) for differentiating chicken MSCs toward spermatogonial stem cells. MSCs were isolated and characterized from chicken and cultured under treatment with all-trans retinoic acid (RA) or glial cell derived neurotrophic factor. Expression analysis of specific genes after 7days of RA treatment, as examined by RT-PCR, proved positive for some germ cell markers such as CVH, STRA8, PLZF and some genes involved in spermatogonial stem cell maintenance like BCL6b and c-KIT. On the other hand, GDNF could additionally induce expression of POU5F1, and NANOG as well as other genes which were induced after RA treatment. These data illustrated that GDNF is relatively more effective in diverting chicken MSCs towards Spermatogonial stem cell -like cells in chickens and suggests GDNF as a new agent to obtain transgenic poultry, nevertheless, exploitability of these cells should be verified by more experiments.

  9. Therapeutic application of mesenchymal stem cell-derived exosomes: A promising cell-free therapeutic strategy in regenerative medicine.

    Science.gov (United States)

    Motavaf, M; Pakravan, K; Babashah, S; Malekvandfard, F; Masoumi, M; Sadeghizadeh, M

    2016-06-30

    Mesenchymal stem cells have emerged as promising therapeutic candidates in regenerative medicine. The mechanisms underlying mesenchymal stem cells regenerative properties were initially attributed to their engraftment in injured tissues and their subsequent transdifferentiation to repair and replace damaged cells. However, studies in animal models and patients indicated that the low number of transplanted mesenchymal stem cells localize to the target tissue and transdifferentiate to appropriate cell lineage. Instead the regenerative potential of mesenchymal stem cells has been found - at least in part - to be mediated via their paracrine actions. Recently, a secreted group of vesicles, called "exosome" has been identified as major mediator of mesenchymal stem cells therapeutic efficacy. In this review, we will summarize the current literature on administration of exosomes released by mesenchymal stem cells in regenerative medicine and suggest how they could help to improve tissue regeneration following injury.

  10. Function of mesenchymal stem cells following loading of gold nanotracers

    Directory of Open Access Journals (Sweden)

    et al

    2011-02-01

    Full Text Available Laura M Ricles1, Seung Yun Nam1,2, Konstantin Sokolov3,1, Stanislav Y Emelianov1,3, Laura J Suggs11Department of Biomedical Engineering, 2Department of Electrical and Computer Engineering, The University of Texas at Austin, Austin, TX, USA; 3Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USABackground: Stem cells can differentiate into multiple cell types, and therefore can be used for cellular therapies, including tissue repair. However, the participation of stem cells in tissue repair and neovascularization is not well understood. Therefore, implementing a noninvasive, long-term imaging technique to track stem cells in vivo is needed to obtain a better understanding of the wound healing response. Generally, we are interested in developing an imaging approach to track mesenchymal stem cells (MSCs in vivo after delivery via a polyethylene glycol modified fibrin matrix (PEGylated fibrin matrix using MSCs loaded with gold nanoparticles as nanotracers. The objective of the current study was to assess the effects of loading MSCs with gold nanoparticles on cellular function.Methods: In this study, we utilized various gold nanoparticle formulations by varying size and surface coatings and assessed the efficiency of cell labeling using darkfield microscopy. We hypothesized that loading cells with gold nanotracers would not significantly alter cell function due to the inert and biocompatible characteristics of gold. The effect of nanoparticle loading on cell viability and cytotoxicity was analyzed using a LIVE/DEAD stain and an MTT assay. The ability of MSCs to differentiate into adipocytes and osteocytes after nanoparticle loading was also examined. In addition, nanoparticle loading and retention over time was assessed using inductively coupled plasma mass spectrometry (ICP-MS.Conclusion: Our results demonstrate that loading MSCs with gold nanotracers does not alter cell function and, based on the ICP

  11. Treatment of osteochondral defects in the rabbit's knee joint by implantation of allogeneic mesenchymal stem cells in fibrin clots.

    Science.gov (United States)

    Berninger, Markus T; Wexel, Gabriele; Rummeny, Ernst J; Imhoff, Andreas B; Anton, Martina; Henning, Tobias D; Vogt, Stephan

    2013-05-21

    bone (11). The sandwich-technique combines bone grafting with current approaches in Tissue Engineering (5,6). This combination seems to be able to overcome the limitations seen in osteochondral grafts alone. After autologous bone grafting to the subchondral defect area, a membrane seeded with autologous chondrocytes is sutured above and facilitates to match the topology of the graft with the injured site. Of course, the previous bone reconstruction needs additional surgical time and often even an additional surgery. Moreover, to date, long-term data is missing (12). Tissue Engineering without additional bone grafting aims to restore the complex structure and properties of native articular cartilage by chondrogenic and osteogenic potential of the transplanted cells. However, again, it is usually only the cartilage tissue that is more or less regenerated. Additional osteochondral damage needs a specific further treatment. In order to achieve a regeneration of the multilayered structure of osteochondral defects, three-dimensional tissue engineered products seeded with autologous/allogeneic cells might provide a good regeneration capacity (11). Beside autologous chondrocytes, mesenchymal stem cells (MSC) seem to be an attractive alternative for the development of a full-thickness cartilage tissue. In numerous preclinical in vitro and in vivo studies, mesenchymal stem cells have displayed excellent tissue regeneration potential (13,14). The important advantage of mesenchymal stem cells especially for the treatment of osteochondral defects is that they have the capacity to differentiate in osteocytes as well as chondrocytes. Therefore, they potentially allow a multilayered regeneration of the defect. In recent years, several scaffolds with osteochondral regenerative potential have therefore been developed and evaluated with promising preliminary results (1,15-18). Furthermore, fibrin glue as a cell carrier became one of the preferred techniques in experimental cartilage

  12. Immortalized mesenchymal stem cells: an alternative to primary mesenchymal stem cells in neuronal differentiation and neuroregeneration associated studies

    Directory of Open Access Journals (Sweden)

    Gong Min

    2011-11-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs can be induced to differentiate into neuronal cells under appropriate cellular conditions and transplanted in brain injury and neurodegenerative diseases animal models for neuroregeneration studies. In contrast to the embryonic stem cells (ESCs, MSCs are easily subject to aging and senescence because of their finite ability of self-renewal. MSCs senescence seriously affected theirs application prospects as a promising tool for cell-based regenerative medicine and tissue engineering. In the present study, we established a reversible immortalized mesenchymal stem cells (IMSCs line by using SSR#69 retrovirus expressing simian virus 40 large T (SV40T antigen as an alternative to primary MSCs. Methods The retroviral vector SSR#69 expressing simian virus 40 large T (SV40T antigen was used to construct IMSCs. IMSCs were identified by flow cytometry to detect cell surface makers. To investigate proliferation and differentiation potential of IMSCs, cell growth curve determination and mesodermal trilineage differentiation tests were performed. Neuronal differentiation characteristics of IMSCs were detected in vitro. Before IMSCs transplantation, we excluded its tumorigenicity in nude mice firstly. The Morris water maze tests and shuttle box tests were performed five weeks after HIBD models received cells transplantation therapy. Results In this study, reversible IMSCs were constructed successfully and had the similar morphology and cell surface makers as primary MSCs. IMSCs possessed better ability of proliferation and anti-senescence compared with primary MSCs, while maintained multilineage differentiation capacity. Neural-like cells derived from IMSCs had similar expressions of neural-specific genes, protein expression patterns and resting membrane potential (RMP compared with their counterparts derived from primary MSCs. There was no bump formation in nude mice subcutaneously injected with IMSCs. IMSCs

  13. Feasibility of human hair follicle-derived mesenchymal stem cells/CultiSpher(®)-G constructs in regenerative medicine.

    Science.gov (United States)

    Li, Pengdong; Liu, Feilin; Wu, Chunling; Jiang, Wenyue; Zhao, Guifang; Liu, Li; Bai, Tingting; Wang, Li; Jiang, Yixu; Guo, Lili; Qi, Xiaojuan; Kou, Junna; Fan, Ruirui; Hao, Deshun; Lan, Shaowei; Li, Yulin; Liu, Jin Yu

    2015-10-01

    The use of human mesenchymal stem cells (hMSCs) in cell therapies has increased the demand for strategies that allow efficient cell scale-up. Preliminary data on the three-dimensional (3D) spinner culture describing the potential use of microcarriers for hMSCs culture scale-up have been reported. We exploited a rich source of autologous stem cells (human hair follicle) and demonstrated the robust in vitro long-term expansion of human hair follicle-derived mesenchymal stem cells (hHF-MSCs) by using CultiSpher(®)-G microcarriers. We analyzed the feasibility of 3D culture by using hHF-MSCs/CultiSpher(®)-G microcarrier constructs for its potential applicability in regenerative medicine by comparatively analyzing the performance of hHF-MSCs adhered to the CultiSpher(®)-G microspheres in 3D spinner culture and those grown on the gelatin-coated plastic dishes (2D culture), using various assays. We showed that the hHF-MSCs seeded at various densities quickly adhered to and proliferated well on the microspheres, thus generating at least hundreds of millions of hHF-MSCs on 1 g of CultiSpher(®)-G within 12 days. This resulted in a cumulative cell expansion of greater than 26-fold. Notably, the maximum and average proliferation rates in 3D culture were significantly greater than that of the 2D culture. However, the hHF-MSCs from both the cultures retained surface marker and nestin expression, proliferation capacity and differentiation potentials toward adipocytes, osteoblasts and smooth muscle cells and showed no significant differences as evidenced by Edu incorporation, cell cycle, colony formation, apoptosis, biochemical quantification and qPCR assays.

  14. Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure.

    Science.gov (United States)

    Worel, Nina; Fritsch, Gerhard; Agis, Hermine; Böhm, Alexandra; Engelich, Georg; Leitner, Gerda C; Geissler, Klaus; Gleixner, Karoline; Kalhs, Peter; Buxhofer-Ausch, Veronika; Keil, Felix; Kopetzky, Gerhard; Mayr, Viktor; Rabitsch, Werner; Reisner, Regina; Rosskopf, Konrad; Ruckser, Reinhard; Zoghlami, Claudia; Zojer, Niklas; Greinix, Hildegard T

    2016-08-31

    Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 10(6) CD34(+) cells/kg for a single or ≥5 × 10(6) CD34(+) cells/kg for a double transplantation and potential differences between G-CSF and chemotherapy-based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34(+) cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9-fold increase in CD34(+) cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 10(6) CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19(+) and natural killer cells were collected after G-CSF. Fifty-two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G-CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.

  15. Icing oral mucositis: Oral cryotherapy in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant.

    Science.gov (United States)

    Chen, Joey; Seabrook, Jamie; Fulford, Adrienne; Rajakumar, Irina

    2017-03-01

    Background Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high-dose melphalan conditioning chemotherapy. Oral cryotherapy has been documented to be potentially effective in reducing oral mucositis. The aim of this study was to examine the effectiveness of the cryotherapy protocol implemented within the hematopoietic stem cell transplant program. Methods A retrospective chart review was conducted of adult multiple myeloma patients who received high-dose melphalan conditioning therapy for autologous hematopoietic stem cell transplant. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints included duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition use. Results One hundred and forty patients were included in the study, 70 patients in both no cryotherapy and cryotherapy groups. Both oral mucositis incidence and severity were found to be significantly lower in the cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy compared to 67 (95.7%) in the no cryotherapy group (p < 0.001). The median oral mucositis severity, assessed using the WHO oral toxicity scale from grade 0-4, experienced in the no group was 2.5 vs. 2 in the cryotherapy group (p = 0.03). Oral mucositis duration and use of parenteral narcotics were also significantly reduced. Duration of hospital stay and use of parenteral nutrition were similar between the two groups. Conclusion The cryotherapy protocol resulted in a significantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inexpensive and generally well-tolerated practice.

  16. Transcriptional Dynamics of Immortalized Human Mesenchymal Stem Cells during Transformation.

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    Masao Takeuchi

    Full Text Available Comprehensive analysis of alterations in gene expression along with neoplastic transformation in human cells provides valuable information about the molecular mechanisms underlying transformation. To further address these questions, we performed whole transcriptome analysis to the human mesenchymal stem cell line, UE6E7T-3, which was immortalized with hTERT and human papillomavirus type 16 E6/E7 genes, in association with progress of transformation in these cells. At early stages of culture, UE6E7T-3 cells preferentially lost one copy of chromosome 13, as previously described; in addition, tumor suppressor genes, DNA repair genes, and apoptosis-activating genes were overexpressed. After the loss of chromosome 13, additional aneuploidy and genetic alterations that drove progressive transformation, were observed. At this stage, the cell line expressed oncogenes as well as genes related to anti-apoptotic functions, cell-cycle progression, and chromosome instability (CIN; these pro-tumorigenic changes were concomitant with a decrease in tumor suppressor gene expression. At later stages after prolong culture, the cells exhibited chromosome translocations, acquired anchorage-independent growth and tumorigenicity in nude mice, (sarcoma and exhibited increased expression of genes encoding growth factor and DNA repair genes, and decreased expression of adhesion genes. In particular, glypican-5 (GPC5, which encodes a cell-surface proteoglycan that might be a biomarker for sarcoma, was expressed at high levels in association with transformation. Patched (Ptc1, the cell surface receptor for hedgehog (Hh signaling, was also significantly overexpressed and co-localized with GPC5. Knockdown of GPC5 expression decreased cell proliferation, suggesting that it plays a key role in growth in U3-DT cells (transformants derived from UE6E7T-3 cells through the Hh signaling pathway. Thus, the UE6E7T-3 cell culture model is a useful tool for assessing the functional

  17. Células-tronco mesenquimais Mesenchymal stem cell

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    Betânia Souza Monteiro

    2010-02-01

    Full Text Available Dentre todas as células-tronco estudadas até o presente momento, as mesenquimais (MSC destacam-se por sua elevada plasticidade, podendo originar tecidos mesodermais e não mesodermais. Além disso, possuem características imunomoduladoras e imunossupressoras que ampliam as possibilidades de utilização terapêutica. As MSC secretam uma grande variedade de citocinas pró e anti-inflamatórias e fatores de crescimento e, por meio dessas moléculas bioativas, proporcionam a modulação da resposta inflamatória, o restabelecimento do suprimento vascular e a reparação adequada do tecido, contribuindo para a homeostasia tissular e imunológica sob condições fisiológicas. Também podem induzir as demais células presentes no nicho tecidual a secretarem outros fatores solúveis que estimulam a diferenciação dessas células indiferenciadas, favorecendo o processo de reparação. A terapia celular com MSC é uma alternativa terapêutica promissora, porém a compreensão da biologia dessas células ainda é uma ciência em formação. Este artigo tem por objetivo realizar uma breve revisão sobre as células mesenquimais indiferenciadas.Of all the stem cells studied so far, the mesenchymal stem cells (MSC stand out for their high plasticity and capacity of generating mesodermal and non-mesodermal tissues. In addition, immunomodulatory and immunosuppressive features that expand possibilities for therapeutic use are present in these cells. A variety of pro and anti-inflammatory cytokines and growth factors are secrete for MSC and provide a modulation of inflammatory response, re-establishment of vascular supply and adequate repair of the tissue, contributing to tissue homeostasis under physiologic conditions. Therefore, they can induce secretion of soluble factors that stimulate their differentiation by other cells present at the niche's tissue, promoting the repair process. Cell therapy using MSC is a promises therapeutic alternative, but

  18. Peripheral blood CD34+ cell count as a predictor of adequacy of hematopoietic stem cell collection for autologous transplantation

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    Combariza, Juan F.

    2016-10-01

    Full Text Available Introduction: In order to carry out an autologous transplantation, hematopoietic stem cells should be mobilized to peripheral blood and later collected by apheresis. The CD34+ cell count is a tool to establish the optimal time to begin the apheresis procedure. Objective: To evaluate the association between peripheral blood CD34+ cell count and the successful collection of hematopoietic stem cells. Materials and methods: A predictive test evaluation study was carried out to establish the usefulness of peripheral blood CD34+ cell count as a predictor of successful stem cell collection in patients that will receive an autologous transplantation. Results: 77 patients were included (median age: 49 years; range: 5-66. The predominant baseline diagnosis was lymphoma (53.2 %. The percentage of patients with successful harvest of hematopoietic stem cells was proportional to the number of CD34+cells in peripheral blood at the end of the mobilization procedure. We propose that more than 15 CD34+cells/μL must be present in order to achieve an adequate collection of hematopoietic stem cells. Conclusion: Peripheral blood CD34+ cell count is a useful tool to predict the successful collection of hematopoietic stem cells.

  19. Bone marrow mesenchymal stem cell therapy in ischemic stroke:mechanisms of action and treatment optimization strategies

    Institute of Scientific and Technical Information of China (English)

    Guihong Li; Fengbo Yu; Ting Lei; Haijun Gao; Peiwen Li; Yuxue Sun; Haiyan Huang; Qingchun Mu

    2016-01-01

    Animal and clinical studies have conifrmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  20. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

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    Seyed Mojtaba Hosseini

    2015-01-01

    Full Text Available Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was evaluated using a 6-point grading scale and the pathological change of ischemic cerebral tissue was observed by hematoxylin-eosin staining. Under the fluorescence microscope, the migration of bone marrow mesenchymal stem cells was examined by PKH labeling. Caspase-3 activity was measured using spectrophotometry. The optimal neurological function recovery, lowest degree of ischemic cerebral damage, greatest number of bone marrow mesenchymal stem cells migrating to peri-ischemic area, and lowest caspase-3 activity in the ischemic cerebral tissue were observed in rats that underwent bone marrow mesenchymal stem cell transplantation at 12 hours after cerebral ischemia. These findings suggest that 12 hours after cerebral ischemia is the optimal time for tail vein injection of bone marrow mesenchymal stem cell transplantation against cerebral ischemia, and the strongest neuroprotective effect of this cell therapy appears at this time.

  1. Visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury

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    Rui-ping Zhang

    2015-01-01

    Full Text Available An important factor in improving functional recovery from spinal cord injury using stem cells is maximizing the number of transplanted cells at the lesion site. Here, we established a contusion model of spinal cord injury by dropping a weight onto the spinal cord at T 7-8 . Superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells were transplanted into the injured spinal cord via the subarachnoid space. An outer magnetic field was used to successfully guide the labeled cells to the lesion site. Prussian blue staining showed that more bone marrow mesenchymal stem cells reached the lesion site in these rats than in those without magnetic guidance or superparamagnetic iron oxide labeling, and immunofluorescence revealed a greater number of complete axons at the lesion site. Moreover, the Basso, Beattie and Bresnahan (BBB locomotor rating scale scores were the highest in rats with superparamagnetic labeling and magnetic guidance. Our data confirm that superparamagnetic iron oxide nanoparticles effectively label bone marrow mesenchymal stem cells and impart sufficient magnetism to respond to the external magnetic field guides. More importantly, superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells can be dynamically and non-invasively tracked in vivo using magnetic resonance imaging. Superparamagnetic iron oxide labeling of bone marrow mesenchymal stem cells coupled with magnetic guidance offers a promising avenue for the clinical treatment of spinal cord injury.

  2. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Seyed Mojtaba Hosseini; Mohammad Farahmandnia; Zahra Razi; Somayeh Delavarifar; Benafsheh Shakibajahromi

    2015-01-01

    Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was evaluated using a 6-point grading scale and the pathological change of ischemic cerebral tissue was observed by hematoxylin-eosin staining. Under the lfuorescence microscope, the migration of bone marrow mesenchymal stem cells was examined by PKH labeling. Caspase-3 activity was measured using spectrophotometry. The optimal neurological function recovery, lowest degree of ischemic cerebral damage, greatest number of bone marrow mesenchymal stem cells migrating to peri-ischemic area, and lowest caspase-3 activity in the ischemic cerebral tissue were observed in rats that underwent bone marrow mesenchymal stem cell transplantation at 12 hours after cerebral ischemia. These ifndings suggest that 12 hours after cerebral ischemia is the optimal time for tail vein injection of bone marrow mesenchymal stem cell transplantation against cerebral ischemia, and the strongest neuroprotective effect of this cell therapy appears at this time.

  3. visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Rui-ping Zhang; Cheng Xu; Yin Liu; Jian-ding Li; Jun Xie

    2015-01-01

    An important factor in improving functional recovery from spinal cord injury using stem cells is maximizing the number of transplanted cells at the lesion site. Here, we established a contusion model of spinal cord injury by dropping a weight onto the spinal cord at T7–8. Superparamagnet-ic iron oxide-labeled bone marrow mesenchymal stem cells were transplanted into the injured spinal cordvia the subarachnoid space. An outer magnetic ifeld was used to successfully guide the labeled cells to the lesion site. Prussian blue staining showed that more bone marrow mesen-chymal stem cells reached the lesion site in these rats than in those without magnetic guidance or superparamagnetic iron oxide labeling, and immunolfuorescence revealed a greater number of complete axons at the lesion site. Moreover, the Basso, Beattie and Bresnahan (BBB) locomotor rating scale scores were the highest in rats with superparamagnetic labeling and magnetic guid-ance. Our data conifrm that superparamagnetic iron oxide nanoparticles effectively label bone marrow mesenchymal stem cells and impart sufficient magnetism to respond to the external magnetic ifeld guides. More importantly, superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells can be dynamically and non-invasively trackedin vivo using magnetic resonance imaging. Superparamagnetic iron oxide labeling of bone marrow mesenchymal stem cells coupled with magnetic guidance offers a promising avenue for the clinical treatment of spinal cord injury.

  4. Titanium phosphate glass microcarriers induce enhanced osteogenic cell proliferation and human mesenchymal stem cell protein expression

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    Nilay J Lakhkar

    2015-11-01

    Full Text Available In this study, we have developed 50- to 100-µm-sized titanium phosphate glass microcarriers (denoted as Ti5 that show enhanced proliferation of human mesenchymal stem cells and MG63 osteosarcoma cells, as well as enhanced human mesenchymal stem cell expression of bone differentiation markers, in comparison with commercially available glass microspheres at all time points. We also demonstrate that these microcarriers provide superior human mesenchymal stem cell proliferation with conventional Dulbecco’s Modified Eagle medium than with a specially developed commercial stem cell medium. The microcarrier proliferative capacity is revealed by a 24-fold increase in MG63 cell numbers in spinner flask bioreactor studies performed over a 7-day period, versus only a 6-fold increase in control microspheres under the same conditions; the corresponding values of Ti5 and control microspheres under static culture are 8-fold and 7-fold, respectively. The capability of guided osteogenic differentiation is confirmed by ELISAs for bone morphogenetic protein-2 and osteopontin, which reveal significantly greater expression of these markers, especially osteopontin, by human mesenchymal stem cells on the Ti5 microspheres than on the control. Scanning electron microscopy and confocal laser scanning microscopy images reveal favorable MG63 and human mesenchymal stem cell adhesion on the Ti5 microsphere surfaces. Thus, the results demonstrate the suitability of the developed microspheres for use as microcarriers in bone tissue engineering applications.

  5. Calcium phosphate thin films enhance the response of human mesenchymal stem cells to nanostructured titanium surfaces

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    Mura M McCafferty

    2014-05-01

    Full Text Available The development of biomaterial surfaces possessing the topographical cues that can promote mesenchymal stem cell recruitment and, in particular, those capable of subsequently directing osteogenic differentiation is of increasing importance for the advancement of tissue engineering. While it is accepted that it is the interaction with specific nanoscale topography that induces mesenchymal stem cell differentiation, the potential for an attendant bioactive chemistry working in tandem with such nanoscale features to enhance this effect has not been considered to any great extent. This article presents a study of mesenchymal stem cell response to conformal bioactive calcium phosphate thin films sputter deposited onto a polycrystalline titanium nanostructured surface with proven capability to directly induce osteogenic differentiation in human bone marrow–derived mesenchymal stem cells. The sputter deposited surfaces supported high levels of human bone marrow–derived mesenchymal stem cell adherence and proliferation, as determined by DNA quantification. Furthermore, they were also found to be capable of directly promoting significant levels of osteogenic differentiation. Specifically, alkaline phosphatase activity, gene expression and immunocytochemical localisation of key osteogenic markers revealed that the nanostructured titanium surfaces and the bioactive calcium phosphate coatings could direct the differentiation towards an osteogenic lineage. Moreover, the addition of the calcium phosphate chemistry to the topographical profile of the titanium was found to induce increased human bone marrow–derived mesenchymal stem cell differentiation compared to that observed for either the titanium or calcium phosphate coating without an underlying nanostructure. Hence, the results presented here highlight that a clear benefit can be achieved from a surface engineering strategy that combines a defined surface topography with an attendant, conformal

  6. Platelet lysates produced from expired platelet concentrates support growth and osteogenic differentiation of mesenchymal stem cells.

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    Sandra Mjoll Jonsdottir-Buch

    Full Text Available BACKGROUND: Mesenchymal stem cells are promising candidates in regenerative cell therapy. Conventional culture methods involve the use of animal substances, specifically fetal bovine serum as growth supplement. Since the use of animal-derived products is undesirable for human applications, platelet lysates produced from human platelets are an attractive alternative. This is especially true if platelet lysates from already approved transfusion units at blood banks can be utilized. The purpose of this study was to produce human platelet lysates from expired, blood bank-approved platelet concentrates and evaluate their use as growth supplement in the culture of mesenchymal stem cells. METHODOLOGY/PRINCIPAL FINDINGS: In this study, bone marrow-derived mesenchymal stem cells were cultured with one of three culture supplements; fetal bovine serum, lysates from freshly prepared human platelet concentrates, or lysates from expired human platelet concentrates. The effects of these platelet-derived culture supplements on basic mesenchymal stem cell characteristics were evaluated. All cultures maintained the typical mesenchymal stem cell surface marker expression, trilineage differentiation potential, and the ability to suppress in vitro immune responses. However, mesenchymal stem cells supplemented with platelet lysates proliferated faster than traditionally cultured cells and increased the expression of the osteogenic marker gene RUNX-2; yet no difference between the use of fresh and expired platelet concentrates was observed. CONCLUSION/SIGNIFICANCE: Our findings suggest that human platelet lysates produced from expired platelet concentrates can be used as an alternative to fetal bovine serum for mesenchymal stem cell culture to the same extent as lysates from fresh platelets.

  7. Epigenetic dysregulation in mesenchymal stem cell aging and spontaneous differentiation.

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    Zhilong Li

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSCs hold great promise for the treatment of difficult diseases. As MSCs represent a rare cell population, ex vivo expansion of MSCs is indispensable to obtain sufficient amounts of cells for therapies and tissue engineering. However, spontaneous differentiation and aging of MSCs occur during expansion and the molecular mechanisms involved have been poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Human MSCs in early and late passages were examined for their expression of genes involved in osteogenesis to determine their spontaneous differentiation towards osteoblasts in vitro, and of genes involved in self-renewal and proliferation for multipotent differentiation potential. In parallel, promoter DNA methylation and hostone H3 acetylation levels were determined. We found that MSCs underwent aging and spontaneous osteogenic differentiation upon regular culture expansion, with progressive downregulation of TERT and upregulation of osteogenic genes such as Runx2 and ALP. Meanwhile, the expression of genes associated with stem cell self-renewal such as Oct4 and Sox2 declined markedly. Notably, the altered expression of these genes were closely associated with epigenetic dysregulation of histone H3 acetylation in K9 and K14, but not with methylation of CpG islands in the promoter regions of most of these genes. bFGF promoted MSC proliferation and suppressed its spontaneous osteogenic differentiation, with corresponding changes in histone H3 acetylation in TERT, Oct4, Sox2, Runx2 and ALP genes. CONCLUSIONS/SIGNIFICANCE: Our results indicate that histone H3 acetylation, which can be modulated by extrinsic signals, plays a key role in regulating MSC aging and differentiation.

  8. Mesenchymal stem cell conditioning promotes rat oligodendroglial cell maturation.

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    Janusz Joachim Jadasz

    Full Text Available Oligodendroglial progenitor/precursor cells (OPCs represent the main cellular source for the generation of new myelinating oligodendrocytes in the adult central nervous system (CNS. In demyelinating diseases such as multiple sclerosis (MS myelin repair activities based on recruitment, activation and differentiation of resident OPCs can be observed. However, the overall degree of successful remyelination is limited and the existence of an MS-derived anti-oligodendrogenic milieu prevents OPCs from contributing to myelin repair. It is therefore of considerable interest to understand oligodendroglial homeostasis and maturation processes in order to enable the development of remyelination therapies. Mesenchymal stem cells (MSC have been shown to exert positive immunomodulatory effects, reduce demyelination, increase neuroprotection and to promote adult neural stem cell differentiation towards the oligodendroglial lineage. We here addressed whether MSC secreted factors can boost the OPC's oligodendrogenic capacity in a myelin non-permissive environment. To this end, we analyzed cellular morphologies, expression and regulation of key factors involved in oligodendroglial fate and maturation of primary rat cells upon incubation with MSC-conditioned medium. This demonstrated that MSC-derived soluble factors promote and accelerate oligodendroglial differentiation, even under astrocytic endorsing conditions. Accelerated maturation resulted in elevated levels of myelin expression, reduced glial fibrillary acidic protein expression and was accompanied by downregulation of prominent inhibitory differentiation factors such as Id2 and Id4. We thus conclude that apart from their suggested application as potential anti-inflammatory and immunomodulatory MS treatment, these cells might also be exploited to support endogenous myelin repair activities.

  9. [Use of mesenchymal stem cells for reparative processes activation in bone jaw tissue in experimental conditions].

    Science.gov (United States)

    Volozhin, A I; Vasil'ev, A Iu; Malyginov, N N; Bulanova, I M; Grigor''ian, A S; Kiseleva, E V; Cherniaev, S E; Tarasenko, I V

    2010-01-01

    In experiment on 12 Chinchilla rabbits dynamics of reparative regeneration was studied at the terms 2 and 4 months. Bone defect in mandible corner was closed by osteoplastic material Gapkol which was covered from inside by allogenic or autologic stem cells received from rabbit adipose tissue. The results of the ray tracing methods of study were verified by SEM and histological methods.

  10. IFNγ and B7-H1 in the immunology of mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Mesenchymal stem cells (MSCs) are found in multiple organs in the fetus,cord blood and adult tissues [1]. However, in adults, the bone marrow is the major source of these stem cells. MSCs surround the blood vessels of bone marrow and are also in contact with the trabeculae [2].

  11. Mesenchymal Stem Cells in the Treatment of Traumatic Brain Injury

    Science.gov (United States)

    Hasan, Anwarul; Deeb, George; Rahal, Rahaf; Atwi, Khairallah; Mondello, Stefania; Marei, Hany Elsayed; Gali, Amr; Sleiman, Eliana

    2017-01-01

    Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. The primary insult to the brain initiates secondary injury cascades consisting of multiple complex biochemical responses of the brain that significantly influence the overall severity of the brain damage and clinical sequelae. The use of mesenchymal stem cells (MSCs) offers huge potential for application in the treatment of TBI. MSCs have immunosuppressive properties that reduce inflammation in injured tissue. As such, they could be used to modulate the secondary mechanisms of injury and halt the progression of the secondary insult in the brain after injury. Particularly, MSCs are capable of secreting growth factors that facilitate the regrowth of neurons in the brain. The relative abundance of harvest sources of MSCs also makes them particularly appealing. Recently, numerous studies have investigated the effects of infusion of MSCs into animal models of TBI. The results have shown significant improvement in the motor function of the damaged brain tissues. In this review, we summarize the recent advances in the application of MSCs in the treatment of TBI. The review starts with a brief introduction of the pathophysiology of TBI, followed by the biology of MSCs, and the application of MSCs in TBI treatment. The challenges associated with the application of MSCs in the treatment of TBI and strategies to address those challenges in the future have also been discussed.

  12. Immunomodulatory effect of Mesenchymal Stem Cells on B cells

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    Marcella eFranquesa

    2012-07-01

    Full Text Available The research on T cell immunosuppression therapies has attracted most of the attention in clinical transplantation. However, B cells and humoral immune responses are increasingly acknowledged as crucial mediators of chronic allograft rejection. Indeed, humoral immune responses can lead to renal allograft rejection even in patients whose cell-mediated immune responses are well controlled. On the other hand, newly studied B cell subsets with regulatory effects have been linked to tolerance achievement in transplantation. Better understanding of the regulatory and effector B cell responses may therefore lead to new therapeutic approaches.Mesenchymal Stem Cells (MSC are arising as a potent therapeutic tool in transplantation due to their regenerative and immunomodulatory properties. The research on MSCs has mainly focused on their effects on T cells and although data regarding the modulatory effects of MSCs on alloantigen-specific humoral response in humans is scarce, it has been demonstrated that MSCs significantly affect B cell functioning. In the present review we will analyze and discuss the results in this field.

  13. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

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    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.

  14. Mesenchymal stem cells: potential in treatment of neurodegenerative diseases.

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    Tanna, Tanmay; Sachan, Vatsal

    2014-01-01

    Mesenchymal Stem Cells or Marrow Stromal Cells (MSCs) have long been viewed as a potent tool for regenerative cell therapy. MSCs are easily accessible from both healthy donor and patient tissue and expandable in vitro on a therapeutic scale without posing significant ethical or procedural problems. MSC based therapies have proven to be effective in preclinical studies for graft versus host disease, stroke, myocardial infarction, pulmonary fibrosis, autoimmune disorders and many other conditions and are currently undergoing clinical trials at a number of centers all over the world. MSCs are also being extensively researched as a therapeutic tool against neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Huntington's disease (HD) and Multiple Sclerosis (MS). MSCs have been discussed with regard to two aspects in the context of neurodegenerative diseases: their ability to transdifferentiate into neural cells under specific conditions and their neuroprotective and immunomodulatory effects. When transplanted into the brain, MSCs produce neurotrophic and growth factors that protect and induce regeneration of damaged tissue. Additionally, MSCs have also been explored as gene delivery vehicles, for example being genetically engineered to over express glial-derived or brain-derived neurotrophic factor in the brain. Clinical trials involving MSCs are currently underway for MS, ALS, traumatic brain injuries, spinal cord injuries and stroke. In the present review, we explore the potential that MSCs hold with regard to the aforementioned neurodegenerative diseases and the current scenario with reference to the same.

  15. Mesenchymal stem cells for the treatment of neurodegenerative disease.

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    Joyce, Nanette; Annett, Geralyn; Wirthlin, Louisa; Olson, Scott; Bauer, Gerhard; Nolta, Jan A

    2010-11-01

    Mesenchymal stem cells/marrow stromal cells (MSCs) present a promising tool for cell therapy, and are currently being tested in US FDA-approved clinical trials for myocardial infarction, stroke, meniscus injury, limb ischemia, graft-versus-host disease and autoimmune disorders. They have been extensively tested and proven effective in preclinical studies for these and many other disorders. There is currently a great deal of interest in the use of MSCs to treat neurodegenerative diseases, in particular for those that are fatal and difficult to treat, such as Huntington's disease and amyotrophic lateral sclerosis. Proposed regenerative approaches to neurological diseases using MSCs include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation into the brain, MSCs promote endogenous neuronal growth, decrease apoptosis, reduce levels of free radicals, encourage synaptic connection from damaged neurons and regulate inflammation, primarily through paracrine actions. MSCs transplanted into the brain have been demonstrated to promote functional recovery by producing trophic factors that induce survival and regeneration of host neurons. Therapies will capitalize on the innate trophic support from MSCs or on augmented growth factor support, such as delivering brain-derived neurotrophic factor or glial-derived neurotrophic factor into the brain to support injured neurons, using genetically engineered MSCs as the delivery vehicles. Clinical trials for MSC injection into the CNS to treat traumatic brain injury and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of neurodegenerative disorders are discussed.

  16. Expression of Neural Markers by Undifferentiated Rat Mesenchymal Stem Cells

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    Dana Foudah

    2012-01-01

    Full Text Available The spontaneous expression of neural markers by mesenchymal stem cells (MSCs has been considered to be a demonstration of MSCs’ predisposition to differentiate towards neural lineages. In view of their application in cell therapy for neurodegenerative diseases, it is very important to deepen the knowledge about this distinctive biological property of MSCs. In this study, we evaluated the expression of neuronal and glial markers in undifferentiated rat MSCs (rMSCs at different culture passages (from early to late. rMSCs spontaneously expressed neural markers depending on culture passage, and they were coexpressed or not with the neural progenitor marker nestin. In contrast, the number of rMSCs expressing mesengenic differentiation markers was very low or even completely absent. Moreover, rMSCs at late culture passages were not senescent cells and maintained the MSC immunophenotype. However, their differentiation capabilities were altered. In conclusion, our results support the concept of MSCs as multidifferentiated cells and suggest the existence of immature and mature neurally fated rMSC subpopulations. A possible correlation between specific MSC subpopulations and specific neural lineages could optimize the use of MSCs in cell transplantation therapy for the treatment of neurological diseases.

  17. Novel supplier of mesenchymal stem cell: subacromial bursa.

    Science.gov (United States)

    Lhee, S-H; Jo, Y H; Kim, B Y; Nam, B M; Nemeno, J G; Lee, S; Yang, W; Lee, J I

    2013-10-01

    Mesenchymal stem cells (MSCs) are multipotent stromal elements that can differentiate into a variety of cell types. MSCs are good sources of therapeutic cells for degenerative diseases. For these reason, many researchers have focused on searching for other sources of MSCs. To obtain MSCs for clinical use requires surgery of the donor that therefore can induce donor morbidity, since the common sources at present are bone marrow and adipose tissues. In this study, we investigated the existence of MSCs in postoperative discarded tissues. Subacromial bursal tissues were obtained from the shoulders of 3 injured patients. The cells from the bursa tissues were isolated through treatment with collagenase. The isolated cells were then seeded and expanded by serial passaging under normal culture system. To evaluate MSC characteristics of the cells, their MSC markers were confirmed by mRNA and protein expression. Multipotent ability was assessed using differentiation media and immunohistochemistry. Cells from the bursa expressed MSCs markers-CD29, CD73, CD90, and PDGFRB (platelet-derived growth factor receptor-beta). Moreover, as to their multipotency, bursal cells differentiated into adipocytes (fat cells), osteocytes (bone cells), and chondrocytes (cartilage cells). In summary, we showed that MSCs could be generated from the subacromial bursa, which is medical waste after surgery.

  18. mTOR and the differentiation of mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Xinxin Xiang; Jing Zhao; Geyang Xu; Yin Li; Weizhen Zhang

    2011-01-01

    The mammalian target of rapamycin (mTOR), an evolutionarily conserved serine-threonine protein kinase,belongs to the phosphoinositide 3-kinase (PI3K)-related kinase family, which contains a lipid kinase-like domain within their C-terminal region. Recent studies have revealed that mTOR as a critical intracellular molecule can sense the extracellular energy status and regulate the cell growth and proliferation in a variety of cells and tissues. This review summarizes our current understanding about the effects of mTOR on cell differentiation and tissue development, with an emphasis on the lineage determination of mesenchymal stem cells, mTOR can promote adipogenesis in white adipocytes, brown adipocytes, and muscle satellite cells, while rapamycin inhibits the adipogenic function of mTOR. mTOR signaling may function to affect osteoblast proliferation and differentiation, however, rapamycin has been reported to either inhibit or promote osteogenesis. Although the precise mechanism remains unclear, mTOR is indispensable for myogenesis. Depending on the cell type, rapamycin has been reported to inhibit, promote, or have no effect on myogenesis.

  19. Mesenchymal stem cell mechanobiology and emerging experimental platforms.

    Science.gov (United States)

    MacQueen, Luke; Sun, Yu; Simmons, Craig A

    2013-07-06

    Experimental control over progenitor cell lineage specification can be achieved by modulating properties of the cell's microenvironment. These include physical properties of the cell adhesion substrate, such as rigidity, topography and deformation owing to dynamic mechanical forces. Multipotent mesenchymal stem cells (MSCs) generate contractile forces to sense and remodel their extracellular microenvironments and thereby obtain information that directs broad aspects of MSC function, including lineage specification. Various physical factors are important regulators of MSC function, but improved understanding of MSC mechanobiology requires novel experimental platforms. Engineers are bridging this gap by developing tools to control mechanical factors with improved precision and throughput, thereby enabling biological investigation of mechanics-driven MSC function. In this review, we introduce MSC mechanobiology and review emerging cell culture platforms that enable new insights into mechanobiological control of MSCs. Our main goals are to provide engineers and microtechnology developers with an up-to-date description of MSC mechanobiology that is relevant to the design of experimental platforms and to introduce biologists to these emerging platforms.

  20. Human Mesenchymal Stem Cell Morphology and Migration on Microtextured Titanium

    Science.gov (United States)

    Banik, Brittany L.; Riley, Thomas R.; Platt, Christina J.; Brown, Justin L.

    2016-01-01

    The implant used in spinal fusion procedures is an essential component to achieving successful arthrodesis. At the cellular level, the implant impacts healing and fusion through a series of steps: first, mesenchymal stem cells (MSCs) need to adhere and proliferate to cover the implant; second, the MSCs must differentiate into osteoblasts; third, the osteoid matrix produced by the osteoblasts needs to generate new bone tissue, thoroughly integrating the implant with the vertebrate above and below. Previous research has demonstrated that microtextured titanium is advantageous over smooth titanium and PEEK implants for both promoting osteogenic differentiation and integrating with host bone tissue; however, no investigation to date has examined the early morphology and migration of MSCs on these surfaces. This study details cell spreading and morphology changes over 24 h, rate and directionality of migration 6–18 h post-seeding, differentiation markers at 10 days, and the long-term morphology of MSCs at 7 days, on microtextured, acid-etched titanium (endoskeleton), smooth titanium, and smooth PEEK surfaces. The results demonstrate that in all metrics, the two titanium surfaces outperformed the PEEK surface. Furthermore, the rough acid-etched titanium surface presented the most favorable overall results, demonstrating the random migration needed to efficiently cover a surface in addition to morphologies consistent with osteoblasts and preosteoblasts. PMID:27243001

  1. Epac Activation Regulates Human Mesenchymal Stem Cells Migration and Adhesion.

    Science.gov (United States)

    Yu, Jiao-Le; Deng, Ruixia; Chung, Sookja K; Chan, Godfrey Chi-Fung

    2016-04-01

    How to enhance the homing of human mesenchymal stem cells (hMSCs) to the target tissues remains a clinical challenge nowadays. To overcome this barrier, the mechanism responsible for the hMSCs migration and engraftment has to be defined. Currently, the exact mechanism involved in migration and adhesion of hMSCs remains unknown. Exchange protein directly activated by cAMP (Epac), a novel protein discovered in cAMP signaling pathway, may have a potential role in regulating cells adhesion and migration by triggering the downstream Rap family signaling cascades. However, the exact role of Epac in cells homing is elusive. Our study evaluated the role of Epac in the homing of hMSCs. We confirmed that hMSCs expressed functional Epac and its activation enhanced the migration and adhesion of hMSCs significantly. The Epac activation was further found to be contributed directly to the chemotactic responses induced by stromal cell derived factor-1 (SDF-1) which is a known chemokine in regulating hMSCs homing. These findings suggested Epac is connected to the SDF-1 signaling cascades. In conclusion, our study revealed that Epac plays a role in hMSCs homing by promoting adhesion and migration. Appropriate manipulation of Epac may enhance the homing of hMSCs and facilitate their future clinical applications.

  2. Mesenchymal Stem Cells Subpopulations: Application for Orthopedic Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Vanessa Pérez-Silos

    2016-01-01

    Full Text Available Research on mesenchymal stem cells (MSCs continues to progress rapidly. Nevertheless, the field faces several challenges, such as inherent cell heterogeneity and the absence of unique MSCs markers. Due to MSCs’ ability to differentiate into multiple tissues, these cells represent a promising tool for new cell-based therapies. However, for tissue engineering applications, it is critical to start with a well-defined cell population. Additionally, evidence that MSCs subpopulations may also feature distinct characteristics and regeneration potential has arisen. In this report, we present an overview of the identification of MSCs based on the expression of several surface markers and their current tissue sources. We review the use of MSCs subpopulations in recent years and the main methodologies that have addressed their isolation, and we emphasize the most-used surface markers for selection, isolation, and characterization. Next, we discuss the osteogenic and chondrogenic differentiation from MSCs subpopulations. We conclude that MSCs subpopulation selection is not a minor concern because each subpopulation has particular potential for promoting the differentiation into osteoblasts and chondrocytes. The accurate selection of the subpopulation advances possibilities suitable for preclinical and clinical studies and determines the safest and most efficacious regeneration process.

  3. Mesenchymal stem cells for treatment of aortic aneurysms

    Institute of Scientific and Technical Information of China (English)

    Aika; Yamawaki-Ogata; Ryotaro; Hashizume; Xian-Ming; Fu; Akihiko; Usui; Yuji; Narita

    2014-01-01

    An aortic aneurysm(AA) is a silent but life-threatening disease that involves rupture. It occurs mainly in aging and severe atherosclerotic damage of the aortic wall. Even though surgical intervention is effective to prevent rupture, surgery for the thoracic and thoraco-abdom-inal aorta is an invasive procedure with high mortality and morbidity. Therefore, an alternative strategy for treatment of AA is required. Recently, the molecular pathology of AA has been clarified. AA is caused by an imbalance between the synthesis and degradation of extracellular matrices in the aortic wall. Chronic inflam-mation enhances the degradation of matrices directly and indirectly, making control of the chronic inflamma-tion crucial for aneurysmal development. Meanwhile, mesenchymal stem cells(MSCs) are known to be ob-tained from an adult population and to differentiate into various types of cells. In addition, MSCs have not only the potential anti-inflammatory and immunosuppres-sive properties but also can be recruited into damagedtissue. MSCs have been widely used as a source for celltherapy to treat various diseases involving graft-versus-host disease, stroke, myocardial infarction, and chronicinflammatory disease such as Crohn’s disease clinically.Therefore, administration of MSCs might be availableto treat AA using anti-inflammatory and immnosup-pressive properties. This review provides a summary ofseveral studies on "Cell Therapy for Aortic Aneurysm"including our recent data, and we also discuss the pos-sibility of this kind of treatment.

  4. Insight into Reepithelialization: How Do Mesenchymal Stem Cells Perform?

    Directory of Open Access Journals (Sweden)

    Deyun Chen

    2016-01-01

    Full Text Available Wound reepithelialization is a cooperative multifactorial process dominated by keratinocyte migration, proliferation, and differentiation that restores the intact epidermal barrier to prevent infection and excessive moisture loss. However, in wounds that exhibit impaired wound healing, such as chronic nonhealing wounds or hypertrophic scars, the reepithelialization process has failed. Thus, it is necessary to explore a suitable way to mitigate these abnormalities to promote reepithelialization and achieve wound healing. Mesenchymal stem cells (MSCs have the capacity for self-renewal as well as potential multipotency. These cells play important roles in many biological processes, including anti-inflammation, cell migration, proliferation, and differentiation, and signal pathway activation or inhibition. The mechanism of the involvement of MSCs in reepithelialization is still not fully understood. An abundance of evidence has shown that MSCs participate in reepithelialization by inhibiting excessive inflammatory responses, secreting important factors, differentiating into multiple skin cell types, and recruiting other host cells. This review describes the evidence for the roles that MSCs appear to play in the reepithelialization process.

  5. Mesenchymal stem cell seeding promotes reendothelialization of the endovascular stent.

    Science.gov (United States)

    Wu, Xue; Wang, Guixue; Tang, Chaojun; Zhang, Dechuan; Li, Zhenggong; Du, Dingyuan; Zhang, Zhengcai

    2011-09-01

    This study is designed to make a novel cell seeding stent and to evaluate reendothelialization and anti-restenosis after the stent implantation. In comparison with cell seeding stents utilized in previous studies, Mesenchymal stem cells (MSCs) have advantages on promoting of issue repair. Thus it was employed to improve the reendothelialization effects of endovascular stent in present work. MSCs were isolated by density gradient centrifugation and determined as CD29(+) CD44(+) CD34(-) cells by immunofluorescence and immunocytochemistry; gluten and polylysine coated stents were prepared by ultrasonic atomization spray, and MSCs seeded stents were made through rotation culture according to the optimized conditions that were determined in previous studies. The results from animal experiments, in which male New Zealand white rabbits were used, show that the reendothelialization of MSCs coated stents can be completed within one month; in comparison with 316L stainless steel stents (316L SS stents) and gluten and polylysine coated stents, the intimal hyperplasia and in-stent restenosis are significantly inhibited by MSCs coated stents. Endovascular stent seeded with MSCs promotes reendothelialization and inhibits the intimal hyperplasia and in-stent restenosis compared with the 316L SS stents and the gluten and polylysine coated stents.

  6. Chondrogenic differentiation of mesenchymal stem cells: challenges and unfulfilled expectations.

    Science.gov (United States)

    Somoza, Rodrigo A; Welter, Jean F; Correa, Diego; Caplan, Arnold I

    2014-12-01

    Articular cartilage repair and regeneration provides a substantial challenge in Regenerative Medicine because of the high degree of morphological and mechanical complexity intrinsic to hyaline cartilage due, in part, to its extracellular matrix. Cartilage remains one of the most difficult tissues to heal; even state-of-the-art regenerative medicine technology cannot yet provide authentic cartilage resurfacing. Mesenchymal stem cells (MSCs) were once believed to be the panacea for cartilage repair and regeneration, but despite years of research, they have not fulfilled these expectations. It has been observed that MSCs have an intrinsic differentiation program reminiscent of endochondral bone formation, which they follow after exposure to specific reagents as a part of current differentiation protocols. Efforts have been made to avoid the resulting hypertrophic fate of MSCs; however, so far, none of these has recreated a fully functional articular hyaline cartilage without chondrocytes exhibiting a hypertrophic phenotype. We reviewed the current literature in an attempt to understand why MSCs have failed to regenerate articular cartilage. The challenges that must be overcome before MSC-based tissue engineering can become a front-line technology for successful articular cartilage regeneration are highlighted.

  7. Mesenchymal stem cells and cancer: friends or enemies?

    Science.gov (United States)

    Hong, In-Sun; Lee, Hwa-Yong; Kang, Kyung-Sun

    2014-10-01

    There is increasing evidence that mesenchymal stem cells (MSCs) have the ability to migrate and engraft into tumor sites and exert stimulatory effects on cancer cell growth, invasion and even metastasis through direct and/or indirect interaction with tumor cells. However, these pro-tumorigenic effects of MSCs are still being discovered and may even involve opposing effects. MSCs can be friends or enemies of cancer cells: they may stimulate tumor development by regulating immune surveillance, growth, and angiogenesis. On the other hand, they may inhibit tumor growth by inhibiting survival signaling such as Wnt and Akt pathway. MSCs have also been proposed as an attractive candidate for the delivery of anti-tumor agents, owing to their ability to home into tumor sites and to secrete cytokines. Detailed information about the mutual interactions between tumor cells and MSCs will undoubtedly lead to safer and more effective clinical therapy for tumors. In this article, we summarize a number of findings to provide current information on the potential roles of MSCs in tumor development; we then discuss the therapeutic potential of engineered MSCs to reveal any meaningful clinical applications.

  8. Mesenchymal Stem Cells Subpopulations: Application for Orthopedic Regenerative Medicine

    Science.gov (United States)

    Camacho-Morales, Alberto

    2016-01-01

    Research on mesenchymal stem cells (MSCs) continues to progress rapidly. Nevertheless, the field faces several challenges, such as inherent cell heterogeneity and the absence of unique MSCs markers. Due to MSCs' ability to differentiate into multiple tissues, these cells represent a promising tool for new cell-based therapies. However, for tissue engineering applications, it is critical to start with a well-defined cell population. Additionally, evidence that MSCs subpopulations may also feature distinct characteristics and regeneration potential has arisen. In this report, we present an overview of the identification of MSCs based on the expression of several surface markers and their current tissue sources. We review the use of MSCs subpopulations in recent years and the main methodologies that have addressed their isolation, and we emphasize the most-used surface markers for selection, isolation, and characterization. Next, we discuss the osteogenic and chondrogenic differentiation from MSCs subpopulations. We conclude that MSCs subpopulation selection is not a minor concern because each subpopulation has particular potential for promoting the differentiation into osteoblasts and chondrocytes. The accurate selection of the subpopulation advances possibilities suitable for preclinical and clinical studies and determines the safest and most efficacious regeneration process. PMID:27725838

  9. Clopidogrel Enhances Mesenchymal Stem Cell Proliferation Following Periodontitis.

    Science.gov (United States)

    Coimbra, L S; Steffens, J P; Alsadun, S; Albiero, M L; Rossa, C; Pignolo, R J; Spolidorio, L C; Graves, D T

    2015-12-01

    Bone formation is dependent on the differentiation of osteoblasts from mesenchymal stem cells (MSCs). In addition to serving as progenitors, MSCs reduce inflammation and produce factors that stimulate tissue formation. Upon injury, MSCs migrate to the periodontium, where they contribute to regeneration. We examined the effect of clopidogrel and aspirin on MSCs following induction of periodontitis in rats by placement of ligatures. We showed that after the removal of ligatures, which induces resolution of periodontal inflammation, clopidogrel had a significant effect on reducing the inflammatory infiltrate. It also increased the number of osteoblasts and MSCs. Mechanistically, the latter was linked to increased proliferation of MSCs in vivo and in vitro. When given prior to inducing periodontitis, clopidogrel had little effect on MSC or osteoblasts numbers. Applying aspirin before or after induction of periodontitis did not have a significant effect on the parameters measured. These results suggest that clopidogrel may have a positive effect on MSCs in conditions where a reparative process has been initiated.

  10. 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.

  11. The Role of Mesenchymal Stem Cell in Cancer Development

    Directory of Open Access Journals (Sweden)

    Hiroshi eYagi

    2013-11-01

    Full Text Available The role of mesenchymal stem cells (MSCs in cancer development is still controversial. MSCs may promote tumor progression through immune modulation, but other tumor suppressive effects of MSCs have also been described. The discrepancy between these results may arise from issues related to different tissue sources, individual donor variability, and injection timing of MSCs. The expression of critical receptors such as Toll-like receptor (TLR is variable at each time point of treatment, which may also determine the effects of MSCs on tumor progression. However, factors released from malignant cells, as well as surrounding tissues and the vasculature, are still regarded as a black box. Thus, it is still difficult to clarify the specific role of MSCs in cancer development. Whether MSCs support or suppress tumor progression is currently unclear, but it is clear that systemically administered MSCs can be recruited and migrate toward tumors. These findings are important because they can be used as a basis for initiating studies to explore the incorporation of engineered MSCs as novel anti-tumor carriers, for the development of tumor-targeted therapies.

  12. Intra-articular Implantation of Mesenchymal Stem Cells, Part 2

    Science.gov (United States)

    Kraeutler, Matthew J.; Mitchell, Justin J.; Chahla, Jorge; McCarty, Eric C.; Pascual-Garrido, Cecilia

    2017-01-01

    Knee osteoarthritis (OA) after partial or total meniscectomy is a prevalent issue that patients must face. Various methods of replacing meniscal tissue have been studied to avoid this progression, including meniscal allograft transplantation, meniscal scaffolds, and synthetic meniscus replacement. Studies have shown that meniscal scaffolds may improve symptoms but have not been shown to prevent progression of OA. Recently, mesenchymal stem cells (MSCs) have been proposed as a possible biological therapy for meniscal regeneration. Several animal studies and 1 human study have evaluated the effect of transplanting MSCs into the knee joint after partial meniscectomy. The purpose of this review was to assess the outcomes of intra-articular transplantation of MSCs on meniscal regeneration in animals and humans after partial meniscectomy. Limited results from animal studies suggest that there is some potential for intra-articular injection of MSCs for the regeneration of meniscal tissue. However, further studies are necessary to determine the quality of regenerated meniscal tissue through histological and biomechanical testing. PMID:28203596

  13. Oxidative stress induces senescence in human mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Brandl, Anita [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Meyer, Matthias; Bechmann, Volker [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Nerlich, Michael [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Angele, Peter, E-mail: Peter.Angele@klinik.uni-regensburg.de [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany)

    2011-07-01

    Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated {beta}-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.

  14. Hydrophilic polyurethane matrix promotes chondrogenesis of mesenchymal stem cells.

    Science.gov (United States)

    Nalluri, Sandeep M; Krishnan, G Rajesh; Cheah, Calvin; Arzumand, Ayesha; Yuan, Yuan; Richardson, Caley A; Yang, Shuying; Sarkar, Debanjan

    2015-09-01

    Segmental polyurethanes exhibit biphasic morphology and can control cell fate by providing distinct matrix guided signals to increase the chondrogenic potential of mesenchymal stem cells (MSCs). Polyethylene glycol (PEG) based hydrophilic polyurethanes can deliver differential signals to MSCs through their matrix phases where hard segments are cell-interactive domains and PEG based soft segments are minimally interactive with cells. These coordinated communications can modulate cell-matrix interactions to control cell shape and size for chondrogenesis. Biphasic character and hydrophilicity of polyurethanes with gel like architecture provide a synthetic matrix conducive for chondrogenesis of MSCs, as evidenced by deposition of cartilage-associated extracellular matrix. Compared to monophasic hydrogels, presence of cell interactive domains in hydrophilic polyurethanes gels can balance cell-cell and cell-matrix interactions. These results demonstrate the correlation between lineage commitment and the changes in cell shape, cell-matrix interaction, and cell-cell adhesion during chondrogenic differentiation which is regulated by polyurethane phase morphology, and thus, represent hydrophilic polyurethanes as promising synthetic matrices for cartilage regeneration.

  15. The Role of Wharton’s Jelly Mesenchymal Stem Cells in Skin Reconstruction

    Directory of Open Access Journals (Sweden)

    Rostamzadeh

    2015-06-01

    Full Text Available Context Stem cell therapy, especially in the segment of mesenchymal stem cells (MSCs, is one of the most promising areas of regenerative medicine. Evidence Acquisition According to research conducted by various researchers, Wharton’s Jelly mesenchymal stem cells (WJMSCs have several advantages compared to others sources, in regenerative medicine: WJMSCs are more primary cells; WJMSCs can be easily isolated and without invasive procedures; WJMSCs have no ethical problems; WJMSCs are more cost effective than other sources of MSCs. Also, WJMSCs were demonstrated to express stem cell mesenchymal markers. Results Similar to bone marrow MSCs, WJMSCs express major histocompatibility complex (MHC class I molecules. Conclusions Although the aforementioned challenges must still be addressed, the potential of WJMSCs in skin regenerative clinical treatments is promising.

  16. Epigenetic remodeling of chromatin architecture: exploring tumor differentiation therapies in mesenchymal stem cells and sarcomas.

    Science.gov (United States)

    Siddiqi, Sara; Mills, Joslyn; Matushansky, Igor

    2010-03-01

    Sarcomas are the mesenchymal-derived malignant tumors of connective tissues (e.g., fat, bone, and cartilage) presumed to arise from aberrant development or differentiation of mesenchymal stem cells (MSCs). Appropriate control of stem cell maintenance versus differentiation allows for normal connective tissue development. Current theories suggest that loss of this control--through accumulation of genetic lesions in MSCs at various points in the differentiation process--leads to development of sarcomas, including undifferentiated, high grade sarcoma tumors. The initiation of stem cell differentiation is highly associated with alteration of gene expression, which depends on chromatin remodeling. Epigenetic chromatin modifying agents have been shown to induce cancer cell differentiation and are currently being used clinically to treat cancer. This review will focus on the importance of epigenetic chromatin remodeling in the context of mesenchymal stem cells, sarcoma tumorigenesis and differentiation therapy.

  17. Autologous Adipose Stem Cell Therapy for Autonomic Nervous System Dysfunction in Two Young Patients

    Science.gov (United States)

    Kamdar, Ankur; Young, Jane; Butler, Ian. J.

    2017-01-01

    Postural orthostatic tachycardia syndrome and neurocardiogenic syncope are clinical manifestations of autonomic nervous system dysfunction (dysautonomia) that can lead to impaired daily functions. We report two young patients presenting with dysautonomia and autoimmune disease who both received autologous adipose stem cells (ASCs) infusions. This report is the first description of ASCs therapy for patients with combined dysautonomia and autoimmune disease. Case 1: A 21-year-old female presented at 12 years of age with escalating severe dysautonomia with weight loss and gastrointestinal symptoms. She had elevated autoantibodies and cytokines and received multiple immune modulation therapies. Her dysautonomia was treated by volume expanders, vasoconstrictors, and beta blockers with mild improvement. She received ASCs about 2 years before this report with dramatic improvement in her dysautonomia and autoimmune symptoms with a 10 kg weight gain. Case 2: A 7-year-old boy presented at 2 years of age with polyarthritis. At 5 years of age, he manifested orthostatic intolerance. He received immune modulatory therapies with mild improvement. He received ASCs and showed marked improvement of his dysautonomia and immune symptoms. Dysautonomia symptoms of these two patients improved significantly after modulation of autoimmune components by ASC therapy. Favorable clinical responses of these two cases warrant further case–control studies. PMID:27959743

  18. NK cell subgroups, phenotype and functions after autologous stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Benedikt eJacobs

    2015-11-01

    Full Text Available High-dose chemotherapy with consecutive autologous stem cell transplantation (autoSCT is a well-established treatment option for patients suffering from malignant lymphoma or multiple myeloma. Natural killer (NK cells are an important part of the immune surveillance, and their cell number after autoSCT is predictive for progression-free and overall survival. To improve knowledge about the role of NK cells after autoSCT, we investigated different NK cell subgroups, their phenotypes and their functions in patients treated with autoSCT. Directly after leukocyte regeneration (>1000 leukocytes/μl following autoSCT, CD56++ NK cells were the major NK cell subset. Surprisingly, these cells showed unusually high surface expression levels of CD57 and KIR compared to expression levels before or at later time points after autoSCT. Moreover, these NK cells strongly up-regulated KIR2DL2/3 and KIR3DL1, whereas KIR2DL1 remained constant, indicating that this cell population arose from more immature NK cells instead of from activated mature ones. Remarkably, NK cells were already able to degranulate and produce IFN-γ and MIP-1β upon tumor interaction early after leukocyte regeneration.In conclusion, we describe an unusual up-regulation of CD57 and KIRs on CD56++ NK cells shortly after autoSCT. Importantly, these NK cells were functionally competent upon tumor interaction at this early time point.

  19. Advancement in high dose therapy and autologous stem cell rescue in lymphoma

    Institute of Scientific and Technical Information of China (English)

    Alessandro; Isidori; Cristina; Clissa; Federica; Loscocco; Barbara; Guiducci; Sara; Barulli; Lara; Malerba; Elisa; Gabucci; Giuseppe; Visani

    2015-01-01

    A lthough advanced stage aggressive non-Hodgkin’slymphomas and Hodgkin’s disease are thought to be che-motherapy-responsive cancers, a considerable number of patients either relapse or never attain a remission. High-dose therapy(HDT) followed by autologous stem cell transplantation(ASCT) is often the only possibility of cure for most of these patients. However, many controversial issues still remain with respect to HDT/ASCT for lymphomas, including its role for, the optimal timing of transplantation, the best conditioning regimen and the potential use of localized radiotherapy or immunologic methods to decrease post-transplant recurrence. Recently, mainly due to the unavailability of carmustine, several novel conditioning protocols have been clinically developed, with the aim of improving the overall outcome by enhancing the anti-lymphoma effect and, at the same time, by reducing short and long-term toxicity. Furthermore, the better safety profiles of novel approaches would definitively allow patients aged more than 65-70 years to benefit from this therapeutic option. In this review, we will briefly discuss the most relevant and recent data available regarding HDT/ASCT in lymphomas.

  20. Autologous peripheral blood stem cell harvest: Collection efficiency and factors affecting it

    Directory of Open Access Journals (Sweden)

    Aseem K Tiwari

    2016-01-01

    Full Text Available Background: Harvest of hematopoietic progenitor cells via leukapheresis is being used increasingly for transplants in India. Adequate yield of cells per kilogram body weight of recipient is required for successful engraftment. Collection efficiency (CE is an objective quality parameter used to assess the quality of leukapheresis program. In this study, we calculated the CE of the ComTec cell separator (Fresenius Kabi, Germany using two different formulae (CE1 and CE2 and analyzed various patient and procedural factors, which may affect it. Materials and Methods: One hundred and one consecutive procedures in 77 autologous donors carried out over 3 years period were retrospectively reviewed. Various characteristics like gender, age, weight, disease status, hematocrit, preprocedure total leukocyte count, preprocedure CD34 positive (CD34+ cells count, preprocedure absolute CD34+ cell count and processed apheresis volume effect on CE were compared. CE for each procedure was calculated using two different formulae, and results were compared using statistical correlation and regression analysis. Results: The mean CE1 and CE2 was 41.2 and 49.1, respectively. CE2 appeared to be more accurate indicator of overall CE as it considered the impact of continued mobilization of stem cells during apheresis procedure, itself. Of all the factors affecting CE, preprocedure absolute CD34+ was the only independent factor affecting CE. Conclusion: The only factor affecting CE was preprocedure absolute CD34+ cells. Though the mean CE2 was higher than CE1, it was not statistically significant.

  1. Stomatitis-related pain in women with breast cancer undergoing autologous hematopoietic stem cell transplant.

    Science.gov (United States)

    Fall-Dickson, Jane M; Mock, Victoria; Berk, Ronald A; Grimm, Patricia M; Davidson, Nancy; Gaston-Johansson, Fannie

    2008-01-01

    The purpose of this cross-sectional, correlational study was to describe stomatitis-related pain in women with breast cancer undergoing autologous hematopoietic stem cell transplant. The hypotheses that significant, positive relationships would exist between oral pain and stomatitis, state anxiety, depression, and alteration in swallowing were tested. Stomatitis, sensory dimension of oral pain, and state anxiety were hypothesized to most accurately predict oral pain overall intensity. Thirty-two women were recruited at 2 East Coast comprehensive cancer centers. Data were collected on bone marrow transplantation day +7 +/- 24 hours using Painometer, Oral Mucositis Index-20, Oral Assessment Guide, State-Trait Anxiety Inventory, and Beck Depression Inventory. Data analysis included descriptive statistics, correlations, and stepwise multiple regression. All participants had stomatitis; 47% had oral pain, with a subset reporting continuous moderate to severe oral pain despite pain management algorithms. Significant, positive associations were seen between oral pain, stomatitis, and alteration in swallowing and between oral pain with swallowing and alteration in swallowing. Oral pain was not significantly correlated with state anxiety and depression. Oral sensory and affective pain intensity most accurately predicted oral pain overall intensity. Future research needs to explore factors that affect perception and response to stomatitis-related oropharyngeal pain and individual patient response to opioid treatment.

  2. The correlation between T regulatory cells and autologous peripheral blood stem cell transplantation in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Ayşe Pınar Erçetin

    2011-06-01

    Full Text Available Objective: Multiple myeloma (MM is characterized by malignant proliferation of plasmocytes and their precursors. T regulatory cells (Tregs have a role in immunosuppression and control of autoimmunity, and are currently an important topic in the study of immune response to tumor cells. The correlation between Tregs and autologous peripheral blood stem cell transplantation (APBSCT in MM has not been studied. The aim of this study was to compare CD4+CD25+FOXP3+ Treg, CD200, and PD-1 levels in MM patients that did and did not undergo APBSCT. Materials and Methods: Peripheral blood samples were collected from 28 MM patients ranging in age from 41 to 78 years for analysis of CD4CD25+ FOXP3+ Tregs, PD-1 (CD279, and CD200. Peripheral blood mononuclear cells were isolated via density gradient centrifugation. Four-color flow cytometry was performed. Using a sequential gating strategy, Tregs were identified as CD4+CD25+FOXP3+ T-cells. Results were analyzed using the Mann Whitney U non-parametric test and a compare means test. p values 0.05. Conclusion: Treg levels were higher in the patients that underwent APBSCT. Tregs are crucial for the induction and maintenance of peripheral tolerance to self-antigens. In addition, Tregs can suppress immune responses to tumor antigens; however, APBSCT and Treg levels were not correlated with CD200 or PD-1 expression. Relationship of Tregs with prognosis needs to be determined by studies that include larger cohorts.

  3. Endometrial regeneration using autologous adult stem cells followed by conception by in vitro fertilization in a patient of severe Asherman′s syndrome

    Directory of Open Access Journals (Sweden)

    Chaitanya B Nagori

    2011-01-01

    Full Text Available In a woman with severe Asherman′s syndrome, curettage followed by placement of intrauterine contraceptive device (IUCD (IUCD with cyclical hormonal therapy was tried for 6 months, for development of the endometrium. When this failed, autologous stem cells were tried as an alternative therapy. From adult autologous stem cells isolated from patient′s own bone marrow, endometrial angiogenic stem cells were separated using immunomagnetic isolation. These cells were placed in the endometrial cavity under ultrasound guidance after curettage. Patient was then given cyclical hormonal therapy. Endometrium was assessed intermittently on ultrasound. On development of endometrium with a thickness of 8 mm and good vascularity, in vitro fertilization and embryo transfer was done. This resulted in positive biochemical pregnancy followed by confirmation of gestational sac, yolk sac, and embryonic pole with cardiac activity on ultrasound. Endometrial angiogenic stem cells isolated from autologous adult stem cells could regenerate injured endometrium not responding to conventional treatment for Asherman′s syndrome.

  4. Evaluation of transport conditions for autologous bone marrow-derived mesenchymal stromal cells for therapeutic application in horses.

    Science.gov (United States)

    Espina, Miguel; Jülke, Henriette; Brehm, Walter; Ribitsch, Iris; Winter, Karsten; Delling, Uta

    2016-01-01

    Background. Mesenchymal stromal cells (MSCs) are increasingly used for clinical applications in equine patients. For MSC isolation and expansion, a laboratory step is mandatory, after which the cells are sent back to the attending veterinarian. Preserving the biological properties of MSCs during this transport is paramount. The goal of the study was to compare transport-related parameters (transport container, media, temperature, time, cell concentration) that potentially influence characteristics of culture expanded equine MSCs. Methods. The study was arranged in three parts comparing (I) five different transport containers (cryotube, two types of plastic syringes, glass syringe, CellSeal), (II) seven different transport media, four temperatures (4 °C vs. room temperature; -20 °C vs. -80 °C), four time frames (24 h vs. 48 h; 48 h vs. 72 h), and (III) three MSC concentrations (5 × 10(6), 10 × 10(6), 20 × 10(6) MSC/ml). Cell viability (Trypan Blue exclusion; percent and total number viable cell), proliferation and trilineage differentiation capacity were assessed for each test condition. Further, the recovered volume of the suspension was determined in part I. Each condition was evaluated using samples of six horses (n = 6) and differentiation protocols were performed in duplicates. Results. In part I of the study, no significant differences in any of the parameters were found when comparing transport containers at room temperature. The glass syringe was selected for all subsequent evaluations (highest recoverable volume of cell suspension and cell viability). In part II, media, temperatures, or time frames had also no significant influence on cell viability, likely due to the large number of comparisons and small sample size. Highest cell viability was observed using autologous bone marrow supernatant as transport medium, and "transport" at 4 °C for 24 h (70.6% vs. control group 75.3%); this was not significant. Contrary, viability was unacceptably low (cell

  5. Mesenchymal stem cells in the dental tissues: perspectives for tissue regeneration.

    Science.gov (United States)

    Estrela, Carlos; Alencar, Ana Helena Gonçalves de; Kitten, Gregory Thomas; Vencio, Eneida Franco; Gava, Elisandra

    2011-01-01

    In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that range from Alzheimer's disease to cardiac ischemia and regenerative medicine, like bone or tooth loss. Based on their ability to rescue and/or repair injured tissue and partially restore organ function, multiple types of stem/progenitor cells have been speculated. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental tissues are considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that these stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. In dentistry, stem cell biology and tissue engineering are of great interest since may provide an innovative for generation of clinical material and/or tissue regeneration. Mesenchymal stem cells were demonstrated in dental tissues, including dental pulp, periodontal ligament, dental papilla, and dental follicle. These stem cells can be isolated and grown under defined tissue culture conditions, and are potential cells for use in tissue engineering, including, dental tissue, nerves and bone regeneration. More recently, another source of stem cell has been successfully generated from human somatic cells into a pluripotent stage, the induced pluripotent stem cells (iPS cells), allowing creation of patient- and disease-specific stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental stem cell an attractive source of mesenchymal stem cells for tissue regeneration. This review describes new findings in the field of dental stem cell research and on their potential use in the tissue regeneration.

  6. Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways.

    Directory of Open Access Journals (Sweden)

    Roy Blum

    Full Text Available BACKGROUND: Signals between stem cells and stroma are important in establishing the stem cell niche. However, very little is known about the regulation of any mammalian stem cell niche as pure isolates of stem cells and their adjacent mesenchyme are not readily available. The prostate offers a unique model to study signals between stem cells and their adjacent stroma as in the embryonic prostate stem cell niche, the urogenital sinus mesenchyme is easily separated from the epithelial stem cells. Here we investigate the distinctive molecular signals of these two stem cell compartments in a mammalian system. METHODOLOGY/PRINCIPAL FINDINGS: We isolated fetal murine urogenital sinus epithelium and urogenital sinus mesenchyme and determined their differentially expressed genes. To distinguish transcripts that are shared by other developing epithelial/mesenchymal compartments from those that pertain to the prostate stem cell niche, we also determined the global gene expression of epidermis and dermis of the same embryos. Our analysis indicates that several of the key transcriptional components that are predicted to be active in the embryonic prostate stem cell niche regulate processes such as self-renewal (e.g., E2f and Ap2, lipid metabolism (e.g., Srebp1 and cell migration (e.g., Areb6 and Rreb1. Several of the enriched promoter binding motifs are shared between the prostate epithelial/mesenchymal compartments and their epidermis/dermis counterparts, indicating their likely relevance in epithelial/mesenchymal signaling in primitive cellular compartments. Based on differential gene expression we also defined ligand-receptor interactions that may be part of the molecular interplay of the embryonic prostate stem cell niche. CONCLUSIONS/SIGNIFICANCE: We provide a comprehensive description of the transcriptional program of the major regulators that are likely to control the cellular interactions in the embryonic prostatic stem cell niche, many of which may

  7. In vivo transplantation of bone marrow mesenchymal stem cells accelerates repair of injured gastric mucosa in rats

    Institute of Scientific and Technical Information of China (English)

    CHANG Qing; YAN Li; WANG Chang-zheng; ZHANG Wen-hui; HU Ya-zhuo; WU Ben-yan

    2012-01-01

    Background Adult stem cells provide a promising alternative for the treatment of injured tissues.We aimed to investigate the effect of in vivo transplantation of bone marrow mesenchymal stem cells (BMMSCs) on injured gastric mucosa in rats.Methods The gastric ulcer in rats was induced by indomethacin.BMMSCs from male rats,labeled with the fluorescent cell linker 5,6-carboxyfluorescein diacetate succinimidyl ester (CFDA SE),were transplanted into the female rats via tail vein injection.The healing process of gastric ulcers was monitored by HE staining.The protein levels of vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR) in the injured gastric mucosa were determined by immunohistochemistry.Results At 48 and 72 hours after BMMSCs transplantation,the CFDA SE labeled cells were found scattered in the injured gastric mucosa,but not in the gastric mucosa of control rats.At 72 hours after BMMSCs transplantation,the mean ulcer index was 12.67±2.16 in the BMMSCs transplanted group and 17.33±1.97 in vehicle-treated controls (P <0.01).Both VEGF and EGFR protein expression levels were significantly higher in the gastric section from the rats that received BMMSCs transplantation as compared to rats without BMMSCs transplantation.Conclusion Autologous BMMSCs transplantation can accelerate gastric ulcer healing in injured gastric mucosa in a rodent model.

  8. GMP-grade human fetal liver-derived mesenchymal stem cells for clinical transplantation.

    Science.gov (United States)

    Larijani, Bagher; Aghayan, Hamid-Reza; Goodarzi, Parisa; Arjmand, Babak

    2015-01-01

    Stem cell therapy seems a promising avenue in regenerative medicine. Within various stem cells, mesenchymal stem cells have progressively used for cellular therapy. Because of the age-related decreasing in the frequency and differentiating capacity of adult MSCs, fetal tissues such as fetal liver, lung, pancreas, spleen, etc. have been introduced as an alternative source of MSCs for cellular therapy. On the other hand, using stem cells as advanced therapy medicinal products, must be performed in compliance with cGMP as a quality assurance system to ensure the safety, quality, and identity of cell products during translation from the basic stem cell sciences into clinical cell transplantation. In this chapter the authors have demonstrated the manufacturing of GMP-grade human fetal liver-derived mesenchymal stem cells.

  9. 自体骨髓间充质干细胞移植对兔角膜碱烧伤炎症反应的抑制作用%Inhibition of bone marrow mesenchymal stem cell autologous transplantation on inflammation following rabbit corneal alkali burn

    Institute of Scientific and Technical Information of China (English)

    吴利安; 王从毅; 杨文; 杨新光; 张林; 王佳慧

    2015-01-01

    .42)/12个视野,差异均有统计学意义(t=10.021、4.832,均P=0.000);移植后14 d和28 d BMSCs组角膜组织中MMP-2蛋白的阳性表达量(A值)分别为0.388±0.016和0.384±0.006,明显低于PBS组的0.438±0.006和0.412±0.005,差异均有统计学意义(t=10.205、13.514,均P=0.000).结论 角膜碱烧伤后早期行自体BMSCs移植可减少PMNs浸润,减轻角膜的炎症反应,下调或抑制MMP-2在受损角膜处的表达,抑制基质胶原纤维的降解,从而减少碱烧伤后角膜溃疡的发生.%Background Ocular alkali burns leads to corneal ulcer and angiogenesis and even corneal opacity.There is still no ideal treatment method.Studies showed that mesenchymal stem cells (MSCs) can repair corneal wound in vivo,but the specific mechanism is still not clear.Objective This study aimed to observe the histopathological change after the early transplatation of bone marrow MSCs (BMSCs) for corneal alkali burn model in rabbits and explore the anti-inflammatory effects of MSCs after corneal alkali burn.Methods Bone marrow of 4 ml was collected from 2-3 month-old Japanese rabbit.BMSCs were isolated and cultured from the bone marrow of rabbits,and the third generation of cells were used in this study.Cultured cells were identified by morphology and the expressions of surface markers.Corneal alkali burn models were extablished in the right eyes of 24 rabbits by attaching the filter paper with 0.1% NaOH at the central cornea for 30 seconds,and then the models were randomized into 2 groups.BMSCs suspension of 300 μl (concentration 5×l06/μl) was subconjunctivally injected 1 hour after modeling in the BMSCs group,and equal volume of PBS was used in the same way in the PBS group.Corneal opacification was scored under the slim lamp microscope in 3,14 and 28 days after injection.The polymorphonuclear neutrophils (PMNs) were counted by histopathological examination,and the expression of matrix metalloproteinase-2 (MMP-2) in the corneal tissue was evaluated by

  10. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Varga, Nora [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Vereb, Zoltan; Rajnavoelgyi, Eva [Department of Immunology, Medical and Health Science Centre, University of Debrecen, Debrecen (Hungary); Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary); Apati, Agota, E-mail: apati@kkk.org.hu [Membrane Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest (Hungary)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth of undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.

  11. The Three-Dimensional Collagen Scaffold Improves the Stemness of Rat Bone Marrow Mesenchymal Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Sufang Han; Yannan Zhao; Zhifeng Xiao; Jin Han; Bing Chen; Lei Chen; Jianwu Dai

    2012-01-01

    Mesenchymal stem cells (MSCs) show the great promise for the treatment of a variety of diseases because of their self-renewal and multipotential abilities.MSCs are generally cultured on two-dimensional (2D) substrate in vitro.There are indications that they may simultaneously lose their stemness and multipotentiality as the result of prolonged 2D culture.In this study,we used three-dimensional (3D) collagen scaffolds as rat MSCs carrier and compared the properties of MSCs on 3D collagen scaffolds with monolayer cultured MSCs.The results demonstrated that collagen scaffolds were suitable for rat MSCs adherence and proliferation.More importantly,compared to MSCs under 2D culture,3D MSCs significantly maintained higher expression levels of stemness genes (Oct4,Sox2,Rex-1 and Nanog),yielded high frequencies of colony-forming units-fibroblastic (CFU-F) and showed enhanced osteogenic and adipogenic differentiation efficiency upon induction.Thus,3D collagen scaffolds may be beneficial for expanding rat MSCs while maintaining the stem cell properties in vitro.

  12. Dorsal root ganglion neurons promote proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Pei-xun Zhang; Xiao-rui Jiang; Lei Wang; Fang-min Chen; Lin Xu; Fei Huang

    2015-01-01

    Preliminary animal experiments have conifrmed that sensory nerve ifbers promote osteoblast differentiation, but motor nerve ifbers have no promotion effect. Whether sensory neurons pro-mote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells remains unclear. No results at the cellular level have been reported. In this study, dorsal root ganglion neurons (sensory neurons) from Sprague-Dawley fetal rats were co-cultured with bone marrow mesenchymal stem cells transfected with green lfuorescent protein 3 weeks after osteo-genic differentiationin vitro, while osteoblasts derived from bone marrow mesenchymal stem cells served as the control group. The rat dorsal root ganglion neurons promoted the prolifera-tion of bone marrow mesenchymal stem cell-derived osteoblasts at 3 and 5 days of co-culture, as observed by lfuorescence microscopy. The levels of mRNAs for osteogenic differentiation-re-lated factors (including alkaline phosphatase, osteocalcin, osteopontin and bone morphogenetic protein 2) in the co-culture group were higher than those in the control group, as detected by real-time quantitative PCR. Our ifndings indicate that dorsal root ganglion neurons promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells, which pro-vides a theoretical basis forin vitro experiments aimed at constructing tissue-engineered bone.

  13. Toll-like receptor 2/6-dependent stimulation of mesenchymal stem cells promotes angiogenesis by paracrine factors

    Directory of Open Access Journals (Sweden)

    H Kokemüller

    2013-09-01

    Full Text Available Reconstruction of critical size bone defects represents a major challenge in orthopaedic surgery. Insufficient angiogenesis is a limiting factor for engraftment of large-scale tissue transplants. Transplantation or stimulation of local mesenchymal stem cells (MSCs represents a potential solution to enhance angiogenesis. We recently identified angiogenic properties for the Toll-like receptor (TLR 2/6 agonist MALP-2 and now investigated if MALP-2 could be used to stimulate MSCs in order to promote angiogenesis in vitro and in vivo.Human MSCs from the bone marrow of healthy subjects were isolated, cultured and expanded in vitro and were shown to be positive for mesenchymal stem cells markers as well as for the MALP-2 receptors TLR2 and TLR6. MALP-2 directly enhanced migration but not proliferation of human MSCs. Conditioned medium from MALP-2 stimulated MSCs significantly increased proliferation, migration and tube formation of endothelial cells. Analysis of the conditioned medium from MSCs revealed that MALP-2 stimulation enhanced the secretion of several chemokines and growth factors including vascular endothelial growth factors (VEGF and granulocyte-macrophage colony-stimulating factor (GM-CSF. Finally, we studied MALP-2 effects on MSCs in a sheep model of tissue engineering in vivo. Therefore, MSCs were isolated from the iliac crest of black head sheep and co-cultivated with MALP-2 ex vivo. Implantation of autologous MSCs within a scaffold cylinder into the M. latissimus dorsi significantly enhanced vessel density of these constructs after 6 months.We here present the first evidence that TLR2/6-dependent stimulation of MSCs promotes angiogenesis in vitro and in vivo offering a novel strategy for therapeutic angiogenesis, e.g., for tissue engineering of bone.

  14. Immunology of Stem Cells and Cancer Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Yang

    2007-01-01

    The capacity of pluri-potent stem cells to repair the tissues in which stem cells reside holds great promise in development of novel cell replacement therapeutics for treating chronic and degenerative diseases. However,numerous reports show that stem cell therapy, even in an autologous setting, triggers lymphocyte infiltration and inflammation. Therefore, an important question to be answered is how the host immune system responds to engrafted autologous stem cells or allogeneous stem cells. In this brief review, we summarize the progress in several related areas in this field, including some of our data, in four sections: (1) immunogenicity of stem cells; (2)strategies to inhibit immune rejection to allograft stem cells; (3) immune responses to cancer stem cells; and (4)mesenchymal stem cells in immune regulation. Improvement of our understanding on these and other aspects of immune system-stem cell interplay would greatly facilitate the development of stem cell-based therapeutics for regenerative purposes.

  15. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells.

    Science.gov (United States)

    Wakao, Shohei; Kuroda, Yasumasa; Ogura, Fumitaka; Shigemoto, Taeko; Dezawa, Mari

    2012-11-08

    Mesenchymal stem cells (MSCs) are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse) cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine.

  16. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells

    Directory of Open Access Journals (Sweden)

    Mari Dezawa

    2012-11-01

    Full Text Available Mesenchymal stem cells (MSCs are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine.

  17. Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth

    OpenAIRE

    Gonzalez, Maria E.; Martin, Emily E.; Talha Anwar; Caroline Arellano-Garcia; Natasha Medhora; Arjun Lama; Yu-Chih Chen; Kevin S. Tanager; Euisik Yoon; Kidwell, Kelley M.; Chunxi Ge; Franceschi, Renny T.; Celina G. Kleer

    2017-01-01

    Increased collagen deposition by breast cancer (BC)-associated mesenchymal stem/multipotent stromal cells (MSC) promotes metastasis, but the mechanisms are unknown. Here, we report that the collagen receptor discoidin domain receptor 2 (DDR2) is essential for stromal-BC communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. In MSCs isolated from human BC metastasis, DDR2 maintains a fibroblastic phenotype with co...

  18. Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions : A pilot study

    NARCIS (Netherlands)

    Geburek, Florian; Mundle, Kathrin; Conrad, Sabine; Hellige, Maren; Walliser, Ulrich; van Schie, Hans T M; van Weeren, René; Skutella, Thomas; Stadler, Peter M

    2016-01-01

    BACKGROUND: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used to treat equine tendinopathies. Up to now, knowledge about the fate of autologous AT-MSCs after intralesional injection into equine superficial digital flexor tendons (SDFTs) is very limited. The purpose of th

  19. Distribution and differentiation of mesenchymal stem cells in tumor tissue

    Institute of Scientific and Technical Information of China (English)

    ZHAO Hai-feng; CHEN Jun; XU Zhi-shun; ZHANG Ke-qin

    2009-01-01

    Background Tumor has an ability to become enriched in mesenchymal stem cells (MSCs) and of guiding MSCs to migrate to tumor tissue. But there are lack of relevant reports on the distribution and differentiation of MSCs in tumor tissue and the effect on tumor growth after MSCs engrafted in tumor tissue. In this study, we observed the distribution of bone marrow MSCs in tumor tissue and the possibility of MSCs differentiating into myofibroblast under the induction of local tumor microenvironment.Methods Twenty-four New Zealand rabbits were randomly classified into the control group and the test group. MSCs were isolated and cultured for each animal, vx-2 tumor tissue was transplanted under the bladder mucosa of each animal. One week after the transplantation, the self F2 passage MSCs marked by 4',6-diamidino-2-phenylindole were transplanted into tumor tissue in the test group while only Dulbecco's modified Eagle's medium-low glucose was infused into the control group. Ultrasonography was performed for each animal 1,2, 3 and 4 week(s) after the vx-2 tumor mass was transplanted. The maximum bladder tumor diameter of each animal was recorded and the mean value of each group was calculated. One animal from each group was sacrificed in the third week and the remaining animals in the fourth week to observe the tumor development. Another animal treated the same as the test group was sacrificed to observe the distribution of MSCs in tumor tissue one week after self MSCs transplantation. Immunofluorescence was used to trace MSCs in tumor tissue. The double labeling immunofluorescence for α-smooth muscle actin (α-SMA) and vimentin was performed to identify whether the MSCs can differentiate into myofibroblast.Results The ultrasonography showed no tumor mass one week after the vx-2 tumor mass transplantation. The mean maximum tumor diameter of the control group and test group was (0.70±0.14) cm and (0.78±0.14) cm, respectively, and there was no significant difference (t=1

  20. Co-transplantation of macaque autologous Schwann cells and human embryonic nerve stem cells in treatment of macaque Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Ying Xia; Chengchuan Jiang; Zuowei Cao; Keshan Shi; Yang Wang

    2012-01-01

    Objective:To investigate the therapeutic effects of co-transplantation with Schwann cells (SCs) and human embryonic nerve stem cells (NSCs) on macaque Parkinson's disease (PD). Methods:Macaque autologous SCs and human embryonic NSCs were adopted for the treatment of macaque PD. Results: Six months after transplantation, positron emission computerized tomography showed that 18F-FP-β-CIT was significantly concentrated in the injured striatum in the co-transplanted group. Immunohistochemical staining of transplanted area tissue showed migration of tyroxine hydroxylase positive cells from the transplant area to the surrounding area was significantly increased in the co-transplanted group. Conclusions: Co-transplantation of SCs and NSCs could effectively cure PD in macaques. SCs harvested from the autologous peripheral nerves can avoid rejection and the ethics problems, so it is expected to be applied clinically.

  1. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure.

    Directory of Open Access Journals (Sweden)

    Biju Parekkadan

    Full Text Available Modulation of the immune system may be a viable alternative in the treatment of fulminant hepatic failure (FHF and can potentially eliminate the need for donor hepatocytes for cellular therapies. Multipotent bone marrow-derived mesenchymal stem cells (MSCs have been shown to inhibit the function of various immune cells by undefined paracrine mediators in vitro. Yet, the therapeutic potential of MSC-derived molecules has not been tested in immunological conditions in vivo. Herein, we report that the administration of MSC-derived molecules in two clinically relevant forms-intravenous bolus of conditioned medium (MSC-CM or extracorporeal perfusion with a bioreactor containing MSCs (MSC-EB-can provide a significant survival benefit in rats undergoing FHF. We observed a cell mass-dependent reduction in mortality that was abolished at high cell numbers indicating a therapeutic window. Histopathological analysis of liver tissue after MSC-CM treatment showed dramatic reduction of panlobular leukocytic infiltrates, hepatocellular death and bile duct duplication. Furthermore, we demonstrate using computed tomography of adoptively transferred leukocytes that MSC-CM functionally diverts immune cells from the injured organ indicating that altered leukocyte migration by MSC-CM therapy may account for the absence of immune cells in liver tissue. Preliminary analysis of the MSC secretome using a protein array screen revealed a large fraction of chemotactic cytokines, or chemokines. When MSC-CM was fractionated based on heparin binding affinity, a known ligand for all chemokines, only the heparin-bound eluent reversed FHF indicating that the active components of MSC-CM reside in this fraction. These data provide the first experimental evidence of the medicinal use of MSC-derived molecules in the treatment of an inflammatory condition and support the role of chemokines and altered leukocyte migration as a novel therapeutic modality for FHF.

  2. Allogeneic Mesenchymal Stem Cell Transplantation in Dogs With Keratoconjunctivitis Sicca

    Science.gov (United States)

    Bittencourt, Maura K. W.; Barros, Michele A.; Martins, João Flávio P.; Vasconcellos, Jose Paulo C.; Morais, Bruna P.; Pompeia, Celine; Bittencourt, Matheus Domingues; Evangelho, Karine dos Santos; Kerkis, Irina; Wenceslau, Cristiane V.

    2016-01-01

    Keratoconjunctivitis sicca (KCS) is a dysfunction in tear production associated with clinical signs, which include conjunctival hyperemia, ocular discharge, discomfort, pain, and, eventually, corneal vascularization and pigmentation. Immunosuppressive drugs are routinely administrated for long periods to treat KCS but with side effects and limited results. Evaluation of the clinical benefits of intralacrimal transplantation of allogeneic mesenchymal stem cells (MSCs) in dogs with mild–moderate and severe KCS was done. A total of 24 eyes with KCS from 15 dogs of different breeds were enrolled in the present study. A single transplantation of MSCs (1 × 106) directly into lacrimal glands (dorsal and third eyelid) was performed. The Schirmer tear tests (STTs) and ocular surface improvements were used to assess short- and long-term effects of these cells. The STTs were carried out on day 0 (before MSCs transplantation) and on days 7, 14, 21, and 28, as well as 6 and 12 months after MSC transplantation. Our data demonstrate that allogeneic MSC transplantation in KCS dogs is safe since no adverse effects were observed immediately after transplantation and in short- and long-term follow-ups. A statistically significant increase in the STT and ocular surface improvements was found in all eyes studied. In all the eyes with mild–moderate KCS, STT values reverted to those of healthy eyes, while in eyes with severe KCS, although complete reversion was not found, there was improvement in tear production and in other clinical signs. Our study shows that a single dose of a low number of MSCs can be used to treat KCS in dogs. In contrast to immunosuppressive drug use, MSC transplantation has an effect over a long period (up to 12 months), even after a single administration, and does not require daily drug administration. PMID:28003932

  3. Defining human mesenchymal stem cell efficacy in vivo

    Directory of Open Access Journals (Sweden)

    Lennon Donald P

    2010-10-01

    Full Text Available Abstract Allogeneic human mesenchymal stem cells (hMSCs can suppress graft versus host disease (GvHD and have profound anti-inflammatory and regenerative capacity in stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of disease. There is significant clinical hMSC variability in efficacy and the ultimate response in vivo. The challenge in hMSC based therapy is defining the efficacy of hMSC in vivo. Models which may provide insight into hMSC bioactivity in vivo would provide a means to distinguish hMSCs for clinical utility. hMSC function has been described as both regenerative and trophic through the production of bioactive factors. The regenerative component involves the multi-potentiality of hMSC progenitor differentiation. The secreted factors generated by the hMSCs are milieu and injury specific providing unique niches for responses in vivo. These bioactive factors are anti-scarring, angiogenic, anti-apoptotic as well as regenerative. Further, from an immunological standpoint, hMSC's can avoid host immune response, providing xenographic applications. To study the in vivo immuno-regulatory effectiveness of hMSCs, we used the ovalbumin challenge model of acute asthma. This is a quick 3 week in vivo pulmonary inflammation model with readily accessible ways of measuring effectiveness of hMSCs. Our data show that there is a direct correlation between the traditional ceramic cube score to hMSCs attenuation of cellular recruitment due to ovalbumin challenge. The results from these studies verify the in vivo immuno-modulator effectiveness of hMSCs and support the potential use of the ovalbumin model as an in vivo model of hMSC potency and efficacy. Our data also support future directions toward exploring hMSCs as an alternative therapeutic for the treatment of airway inflammation associated with asthma.

  4. Isolation of Mesenchymal Stem Cells from Human Deciduous Teeth Pulp

    Science.gov (United States)

    Tsai, Aileen I.; Hong, Hsiang-Hsi; Fu, Jen-Fen; Chang, Chih-Chun; Wang, I-Kuan; Huang, Wen-Hung; Weng, Cheng-Hao; Hsu, Ching-Wei

    2017-01-01

    This study aimed to identify predictors of success rate of mesenchymal stem cell (MSC) isolation from human deciduous teeth pulp. A total of 161 deciduous teeth were extracted at the dental clinic of Chang Gung Memorial Hospital. The MSCs were isolated from dental pulps using a standard protocol. In total, 128 colonies of MSCs were obtained and the success rate was 79.5%. Compared to teeth not yielding MSCs successfully, those successfully yielding MSCs were found to have less severe dental caries (no/mild-to-moderate/severe: 63.3/24.2/12.5% versus 12.5/42.4/42.4%, P < 0.001) and less frequent pulpitis (no/yes: 95.3/4.7% versus 51.5/48.5%, P < 0.001). In a multivariate regression model, it was confirmed that the absence of dental caries (OR = 4.741, 95% CI = 1.564–14.371, P = 0.006) and pulpitis (OR = 9.111, 95% CI = 2.921–28.420, P < 0.001) was significant determinants of the successful procurement of MSCs. MSCs derived from pulps with pulpitis expressed longer colony doubling time than pulps without pulpitis. Furthermore, there were higher expressions of proinflammatory cytokines, interleukin- (IL-) 6 and monocyte chemoattractant protein- (MCP-) 1, P < 0.01, and innate immune response [toll-like receptor 1 (TLR1) and TLR8, P < 0.05; TLR2, TLR3, and TLR6, P < 0.01] in the inflamed than noninflamed pulps. Therefore, a carious deciduous tooth or tooth with pulpitis was relatively unsuitable for MSC processing and isolation. PMID:28377925

  5. Human dental pulp mesenchymal stem cells isolation and osteoblast differentiation

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    Moustafa Alkhalil

    2015-02-01

    Full Text Available Aim This study was focused on the isolation and characterization of mesenchymal stem cells (MSCs from human dental pulp (DPSC. Methods The study was performed in the Department for Oral and Cranio-Maxillo- Facial Surgey Hamad Medical Corporation, Doha, Qatar and Weill Cornell Medical Colleague Doha, Qatar, in period 2010-2011. Dental pulp was extracted from premolars and third molars of 19 healthy patients. The pulp was digested in a solution of 3 mg/mL collagenase type I and 4 mg/mL dispase for 1 hour at 37C. After filtration, cells were cultured in Dulbecco’s Modified Eagle Medium (DMEM Low Glucoses with 20% Fetal Bovine Serum (FBS, 2mM L-glutamine and antibiotics (100 U/mL penicillin, 100 ug/mL streptomycin at 37 °C under 5% CO2. Cultures were treated with osteoinductive medium for differentiation MSC in to the osteoblast cell line. Staining with Alizarin red were used for the detection of the osteoblast production and calcification new formed tissue. Results On the total of three out of 19 patients it was possible to isolate DPMSCs after 2 to 3 weeks: in one patient it was not possible to expand MSCs because of infection, and in other two patients positive Alizarin red staining reaction showed osteogenic differentiation capability and strong mineralization in vitro. Conclusion The main advantage of using DPSC is absence of morbidity. MSCs could be isolated noninvasively from teeth, routinely extracted in the clinic and discarded as medical waste. Standardization of clinical and laboratory protocols for DPMSCs isolation and team work coordination could lead to significantly improved result.

  6. Secretion of immunoregulatory cytokines by mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Dobroslav; Kyurkchiev; Ivan; Bochev; Ekaterina; Ivanova-Todorova; Milena; Mourdjeva; Tsvetelina; Oreshkova; Kalina; Belemezova; Stanimir; Kyurkchiev

    2014-01-01

    According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.

  7. Mesenchymal stem cells cultured on magnetic nanowire substrates

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    Perez, Jose E.; Ravasi, Timothy; Kosel, Jürgen

    2017-02-01

    Stem cells have been shown to respond to extracellular mechanical stimuli by regulating their fate through the activation of specific signaling pathways. In this work, an array of iron nanowires (NWs) aligned perpendicularly to the surface was fabricated by pulsed electrodepositon in porous alumina templates followed by a partial removal of the alumina to reveal 2-3 μm of the NWs. This resulted in alumina substrates with densely arranged NWs of 33 nm in diameter separated by 100 nm. The substrates were characterized by scanning electron microscopy (SEM) energy dispersive x-ray analysis and vibrating sample magnetometer. The NW array was then used as a platform for the culture of human mesenchymal stem cells (hMSCs). The cells were stained for the cell nucleus and actin filaments, as well as immuno-stained for the focal adhesion protein vinculin, and then observed by fluorescence microscopy in order to characterize their spreading behavior. Calcein AM/ethidium homodimer-1 staining allowed the determination of cell viability. The interface between the cells and the NWs was studied using SEM. Results showed that hMSCs underwent a re-organization of actin filaments that translated into a change from an elongated to a spherical cell shape. Actin filaments and vinculin accumulated in bundles, suggesting the attachment and formation of focal adhesion points of the cells on the NWs. Though the overall number of cells attached on the NWs was lower compared to the control, the attached cells maintained a high viability (>90%) for up to 6 d. Analysis of the interface between the NWs and the cells confirmed the re-organization of F-actin and revealed the adhesion points of the cells on the NWs. Additionally, a net of filopodia surrounded each cell, suggesting the probing of the array to find additional adhesion points. The cells maintained their round shape for up to 6 d of culture. Overall, the NW array is a promising nanostructured platform for studying and influencing h

  8. Mesenchymal stem cells cultured on magnetic nanowire substrates

    KAUST Repository

    Perez, Jose E

    2016-12-28

    Stem cells have been shown to respond to extracellular mechanical stimuli by regulating their fate through the activation of specific signaling pathways. In this work, an array of iron nanowires (NWs) aligned perpendicularly to the surface was fabricated by pulsed electrodepositon in porous alumina templates followed by a partial removal of the alumina to reveal 2-3 μm of the NWs. This resulted in alumina substrates with densely arranged NWs of 33 nm in diameter separated by 100 nm. The substrates were characterized by scanning electron microscopy (SEM) energy dispersive x-ray analysis and vibrating sample magnetometer. The NW array was then used as a platform for the culture of human mesenchymal stem cells (hMSCs). The cells were stained for the cell nucleus and actin filaments, as well as immuno-stained for the focal adhesion protein vinculin, and then observed by fluorescence microscopy in order to characterize their spreading behavior. Calcein AM/ethidium homodimer-1 staining allowed the determination of cell viability. The interface between the cells and the NWs was studied using SEM. Results showed that hMSCs underwent a re-organization of actin filaments that translated into a change from an elongated to a spherical cell shape. Actin filaments and vinculin accumulated in bundles, suggesting the attachment and formation of focal adhesion points of the cells on the NWs. Though the overall number of cells attached on the NWs was lower compared to the control, the attached cells maintained a high viability (>90%) for up to 6 d. Analysis of the interface between the NWs and the cells confirmed the re-organization of F-actin and revealed the adhesion points of the cells on the NWs. Additionally, a net of filopodia surrounded each cell, suggesting the probing of the array to find additional adhesion points. The cells maintained their round shape for up to 6 d of culture. Overall, the NW array is a promising nanostructured platform for studying and influencing h

  9. Migration capacity of human umbilical cord mesenchymal stem cells towards glioma in vivo*

    Institute of Scientific and Technical Information of China (English)

    Cungang Fan; Dongliang Wang; Qingjun Zhang; Jingru Zhou

    2013-01-01

    High-grade glioma is the most common malignant primary brain tumor in adults. The poor prognosis of glioma, combined with a resistance to currently available treatments, necessitates the ment of more effective tumor-selective therapies. Stem cel-based therapies are emerging as novel cel-based delivery vehicle for therapeutic agents. In the present study, we successful y isolated human umbilical cord mesenchymal stem cel s by explant culture. The human umbilical cord senchymal stem cel s were adherent to plastic surfaces, expressed specific surface phenotypes of mesenchymal stem cel s as demonstrated by flow cytometry, and possessed multi-differentiation potentials in permissive induction media in vitro. Furthermore, human umbilical cord mesenchymal stem cel s demonstrated excel ent glioma-specific targeting capacity in established rat glioma models after intratumoral injection or contralateral ventricular administration in vivo. The excellent glioma-specific targeting ability and extensive intratumoral distribution of human umbilical cord mesenchymal stem cel s indicate that they may serve as a novel cel ular vehicle for delivering the-rapeutic molecules in glioma therapy.

  10. Umbilical cord mesenchymal stem cell transplantation for the treatment of Duchenne muscular dystrophy

    Institute of Scientific and Technical Information of China (English)

    Xiaofeng Yang; Yanxiang Wu; Xinping Liu; Yifeng Xu; Naiwu Lü; Yibin Zhang; Hongmei Wang; Xin Lü; Jiping Cui; Jinxu Zhou; Hong Shan

    2011-01-01

    Due to their relative abundance, stable biological properties and excellent reproductive activity,umbilical cord mesenchymal stem cells have previously been utilized for the treatment of Duchenne muscular dystrophy, which is a muscular atrophy disease. Three patients who were clinically and pathologically diagnosed with Duchenne muscular dystrophy were transplanted with umbilical cord mesenchymal stem cells by intravenous infusion, in combination with multi-point intramuscular injection. They were followed up for 12 months after cell transplantation. Results showed that clinical symptoms significantly improved, daily living activity and muscle strength were enhanced,the sero-enzyme, electromyogram, and MRI scans showed improvement, and dystrophin was expressed in the muscle cell membrane. Hematoxylin-eosin staining of a muscle biopsy revealed that muscle fibers were well arranged, fibrous degeneration was alleviated, and fat infiltration was improved. These pieces of evidence suggest that umbilical cord mesenchymal stem cell transplantation can be considered as a new regimen for Duchenne muscular dystrophy.

  11. Gene expression profiles of human bone marrow derived mesenchymal stem cells and tendon cells

    Institute of Scientific and Technical Information of China (English)

    胡庆柳; 朴英杰; 邹飞

    2003-01-01

    Objective To study the gene expression profiles of human bone marrow derived mesenchymal stem cells and tendon cells.Methods Total RNA extracted from human bone marrow derived mesenchymal stem cells and tendon cells underwent reverse transcription, and the products were labeled with α-32P dCTP. The cDNA probes of total RNA were hybridized to cDNA microarray with 1176 genes, and then the signals were analyzed by AtlasImage analysis software Version 1.01a.Results Fifteen genes associated with cell proliferation and signal transduction were up-regulated, and one gene that takes part in cell-to-cell adhesion was down-regulated in tendon cells.Conclusion The 15 up-regulated and one down-regulated genes may be beneficial to the orientational differentiation of mesenchymal stem cells into tendon cells.

  12. Technologies enabling autologous neural stem cell-based therapies for neurodegenerative disease and injury

    Science.gov (United States)

    Bakhru, Sasha H.

    The intrinsic abilities of mammalian neural stem cells (NSCs) to self-renew, migrate over large distances, and give rise to all primary neural cell types of the brain offer unprecedented opportunity for cell-based treatment of neurodegenerative diseases and injuries. This thesis discusses development of technologies in support of autologous NSC-based therapies, encompassing harvest of brain tissue biopsies from living human patients; isolation of NSCs from harvested tissue; efficient culture and expansion of NSCs in 3D polymeric microcapsule culture systems; optimization of microcapsules as carriers for efficient in vivo delivery of NSCs; genetic engineering of NSCs for drug-induced, enzymatic release of transplanted NSCs from microcapsules; genetic engineering for drug-induced differentiation of NSCs into specific therapeutic cell types; and synthesis of chitosan/iron-oxide nanoparticles for labeling of NSCs and in vivo tracking by cellular MRI. Sub-millimeter scale tissue samples were harvested endoscopically from subventricular zone regions of living patient brains, secondary to neurosurgical procedures including endoscopic third ventriculostomy and ventriculoperitoneal shunt placement. On average, 12,000 +/- 3,000 NSCs were isolated per mm 3 of subventricular zone tissue, successfully demonstrated in 26 of 28 patients, ranging in age from one month to 68 years. In order to achieve efficient expansion of isolated NSCs to clinically relevant numbers (e.g. hundreds of thousands of cells in Parkinson's disease and tens of millions of cells in multiple sclerosis), an extracellular matrix-inspired, microcapsule-based culture platform was developed. Initial culture experiments with murine NSCs yielded unprecedented expansion folds of 30x in 5 days, from initially minute NSC populations (154 +/- 15 NSCs per 450 mum diameter capsule). Within 7 days, NSCs expanded as almost perfectly homogenous populations, with 94.9% +/- 4.1% of cultured cells staining positive for

  13. Genetic engineering of mesenchymal stem cells and its application in human disease therapy.

    Science.gov (United States)

    Hodgkinson, Conrad P; Gomez, José A; Mirotsou, Maria; Dzau, Victor J

    2010-11-01

    The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, and neurological and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is being explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis on genetic modifications aimed to improve survival, homing, angiogenesis, and heart function after myocardial infarction. Advancements in other disease areas are also discussed.

  14. Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Espinoza I

    2013-09-01

    Full Text Available Ingrid Espinoza,1,2 Radhika Pochampally,1,2 Fei Xing,1 Kounosuke Watabe,1,3 Lucio Miele1,4 1Cancer Institute, 2Department of Biochemistry, 3Department of Microbiology, 4Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA Abstract: Notch signaling is an evolutionarily conserved pathway involved in cell fate control during development, stem cell self-renewal, and postnatal tissue differentiation. Roles for Notch in carcinogenesis, the biology of cancer stem cells, tumor angiogenesis, and epithelial-to-mesenchymal transition (EMT have been reported. This review describes the role of Notch in the “stemness” program in cancer cells and in metastases, together with a brief update on the Notch inhibitors currently under investigation in oncology. These agents may be useful in targeting cancer stem cells and to reverse the EMT process. Keywords: Notch signaling, EMT, cancer stem cells, mesenchymal stem cells, metastases, Notch inhibitors

  15. Plasticity between Epithelial and Mesenchymal States Unlinks EMT from Metastasis-Enhancing Stem Cell Capacity

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    Evelyne Beerling

    2016-03-01

    Full Text Available Forced overexpression and/or downregulation of proteins regulating epithelial-to-mesenchymal transition (EMT has been reported to alter metastasis by changing migration and stem cell capacity of tumor cells. However, these manipulations artificially keep cells in fixed states, while in vivo cells may adapt transient and reversible states. Here, we have tested the existence and role of epithelial-mesenchymal plasticity in metastasis of mammary tumors without artificially modifying EMT regulators. In these tumors, we found by intravital microscopy that the motile tumor cells have undergone EMT, while their epithelial counterparts were not migratory. Moreover, we found that epithelial-mesenchymal plasticity renders any EMT-induced stemness differences, as reported previously, irrelevant for metastatic outgrowth, because mesenchymal cells that arrive at secondary sites convert to the epithelial state within one or two divisions, thereby obtaining the same stem cell potential as their arrived epithelial counterparts. We conclude that epithelial-mesenchymal plasticity supports migration but additionally eliminates stemness-enhanced metastatic outgrowth differences.

  16. Spontaneous transformation of adult mesenchymal stem cells from cynomolgus macaques in vitro

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    Ren, Zhenhua [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Department of Anatomy, Anhui Medical University, Hefei, 230032 (China); Wang, Jiayin; Zhu, Wanwan; Guan, Yunqian; Zou, Chunlin [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Chen, Zhiguo, E-mail: chenzhiguo@gmail.com [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China); Stanford Institute for Stem Cell Biology and Regenerative Medicine and Department of Neurosurgery, Stanford, CA (United States); Zhang, Y. Alex, E-mail: yaz@bjsap.org [Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing (China); Key Laboratory of Neurodegeneration, Ministry of Education, Beijing (China)

    2011-12-10

    Mesenchymal stem cells (MSCs) have shown potential clinical utility in cell therapy and tissue engineering, due to their ability to proliferate as well as to differentiate into multiple lineages, including osteogenic, adipogenic, and chondrogenic specifications. Therefore, it is crucial to assess the safety of MSCs while extensive expansion ex vivo is a prerequisite to obtain the cell numbers for cell transplantation. Here we show that MSCs derived from adult cynomolgus monkey can undergo spontaneous transformation following in vitro culture. In comparison with MSCs, the spontaneously transformed mesenchymal cells (TMCs) display significantly different growth pattern and morphology, reminiscent of the characteristics of tumor cells. Importantly, TMCs are highly tumorigenic, causing subcutaneous tumors when injected into NOD/SCID mice. Moreover, no multiple differentiation potential of TMCs is observed in vitro or in vivo, suggesting that spontaneously transformed adult stem cells may not necessarily turn into cancer stem cells. These data indicate a direct transformation of cynomolgus monkey MSCs into tumor cells following long-term expansion in vitro. The spontaneous transformation of the cultured cynomolgus monkey MSCs may have important implications for ongoing clinical trials and for models of oncogenesis, thus warranting a more strict assessment of MSCs prior to cell therapy. -- Highlights: Black-Right-Pointing-Pointer Spontaneous transformation of cynomolgus monkey MSCs in vitro. Black-Right-Pointing-Pointer Transformed mesenchymal cells lack multipotency. Black-Right-Pointing-Pointer Transformed mesenchymal cells are highly tumorigenic. Black-Right-Pointing-Pointer Transformed mesenchymal cells do not have the characteristics of cancer stem cells.

  17. Towards Personalized Regenerative Cell Therapy: Mesenchymal Stem Cells Derived from Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Lin, Lin; Bolund, Lars; Luo, Yonglun

    2016-01-01

    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 the importance of choosing the right sources of iPSCs, iPSC reprogramming methods, iPSC culture systems, embryoid body intermediates, pathway inhibitors, basal medium, serum, growth factors and culture surface coating. We also highlight some progress in the application of iPSC-MSCs in direct cell therapy, tissue engineering and gene therapy.

  18. High dose chemotherapy with autologous stem cell transplantation in diffuse large B-cell lymphoma

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    Popp, Henning

    2007-06-01

    Full Text Available Background: High-dose chemotherapy (HDT with autologous stem cell transplantation (ASCT plays an important role in the treatment of aggressive non-Hodgkin’s lymphoma (NHL. We report on a retrospective analysis of all patients with diffuse large B-cell lymphoma who were consecutively treated with HDT followed by ASCT at the University Hospital of Bonn, Germany, between 1996 and 2004. Methods: A total of 25 patients were transplanted for biopsy-proven diffuse large B-cell lymphoma (DLBCL. Eight patients received up-front HDT as first-line therapy, four patients received HDT due to incomplete response to conventional induction chemotherapy, and six patients were treated for primary refractory disease. Seven patients had recurrent lymphoma. Results: A complete remission (CR was achieved in 14 of 25 patients (56%. Estimated 3-year survival for patients treated with upfront HDT, chemosensitive patients with incomplete response to first line therapy, and patients with chemosensitive relapsed disease was 87.5%, 50.0% and 60.0%, respectively. In contrast, no patient with primary refractory disease or relapsed disease lacking chemosensitivity lived longer than 8 months. Chemosensitivity was the only significant prognostic factor for overall survival (OS in multivariate analysis. Conclusions: Our results confirm that HDT and ASCT is a highly effective therapy in patients with DLBCL leading to long-term survival in a substantial proportion of patients. Patients treated upfront for high-risk disease, incomplete response to conventional first-line therapy, or for chemosensitive relapse have a good prognosis. In contrast, patients with primary chemorefractory disease and patients with relapsed disease lacking chemosensitivity do not benefit from HDT with ASCT.

  19. Outcomes in patients with multiple myeloma with TP53 deletion after autologous hematopoietic stem cell transplant.

    Science.gov (United States)

    Gaballa, Sameh; Saliba, Rima M; Srour, Samer; Lu, Gary; Brammer, Jonathan E; Shah, Nina; Bashir, Qaiser; Patel, Krina; Bock, Fabian; Parmar, Simrit; Hosing, Chitra; Popat, Uday; Delgado, Ruby; Rondon, Gabriela; Shah, Jatin J; Manasanch, Elisabet E; Orlowski, Robert Z; Champlin, Richard; Qazilbash, Muzaffar H

    2016-10-01

    TP53 gene deletion is associated with poor outcomes in multiple myeloma (MM). We report the outcomes of patients with MM with and without TP53 deletion who underwent immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) induction followed by autologous hematopoietic stem cell transplant (auto-HCT). We identified 34 patients with MM and TP53 deletion who underwent IMiD and/or PI induction followed by auto-HCT at our institution during 2008-2014. We compared their outcomes with those of control patients (n = 111) with MM without TP53 deletion. Median age at auto-HCT was 59 years in the TP53-deletion group and 58 years in the control group (P = 0.4). Twenty-one patients (62%) with TP53 deletion and 69 controls (62%) achieved at least partial remission before auto-HCT (P = 0.97). Twenty-three patients (68%) with TP53 deletion and 47 controls (42%) had relapsed disease at auto-HCT (P = 0.01). Median progression-free survival was 8 months for patients with TP53 deletion and 28 months for controls (P TP53 deletion and 56 months for controls (P TP53 deletion (hazard ratio 3.4, 95% confidence interval 1.9-5.8, P TP53 deletion and relapsed disease at the time of auto-HCT are independent predictors of progression. Novel approaches should be evaluated in this high-risk population. Am. J. Hematol. 91:E442-E447, 2016. © 2016 Wiley Periodicals, Inc.

  20. Quality of life before autologous stem cells transplantation as prognostic factor in patients with malignant lymphomas

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    Yu. L. Shevchenko

    2014-01-01

    Full Text Available Currently high-doses chemotherapy (HD-PCT + autologous hematopoietic stem cells transplantation (auto-HSCT is the treatment ofchoice in patients with recurrent and progressive lymphomas. Most of quality of life (QoL studies in lymphomas patients received HSCT limited on parameters dynamics assessment in the early and late post-transplant period. Aim of this study was to evaluate the QoL parameters and their prognostic significance in lymphoma patients before transplantation. 124 patients with lymphomas (non-Hodgkin lymphomas – 45 patients, Hodgkin's lymphoma – 79 patients who received HD-PCT + auto-HSCT were included in the study: men – 42.7 % (n = 53, women – 57.3 % (n = 71, median age – 34 years (19–65 years. Patients’ heterogeneity before transplantation regarding quality of life has been revealed. Almost 1/3 of patients showed a significant reduction in the integral index of QoL. Insignificant differences between patients with chemosensitivity and chemoresistant lymphomas regarding QoL before HD-PCT + auto-HSCT were shown. We also analyzed the outcomes of studied patients received HD-PCT + auto-HSCT. With a median follow-up of 18 months, overall survival after transplantation was 72 % (95 % CI 56–84; event-free survival – 64 % (95 % CI 53,3–73,2.Overall and event-free survivals were significantly higher in patients with chemosensitive lymphoma compared with chemoresistance tumor. Differences in the survival rates between patients with no or negligible decrease of QoL integral index and with significant reduction of it also were found. Revealed differences in overall and event-free survival between the groups allowed the first group considered as patients with a favorable prognosis, and the second group – as patients with poor prognosis regarding the transplantation outcome.

  1. Induction therapy pre-autologous stem cell transplantation in immunoglobulin light chain amyloidosis: a retrospective evaluation.

    Science.gov (United States)

    Hwa, Yi L; Kumar, Shaji K; Gertz, Morie A; Lacy, Martha Q; Buadi, Francis K; Kourelis, Taxiarchis V; Gonsalves, Wilson I; Rajkumar, S Vincent; Go, Ronald S; Leung, Nelson; Kapoor, Prashant; Dingli, David; Kyle, Robert A; Russell, Stephen; Lust, John A; Hayman, Suzanne R; Lin, Yi; Zeldenrust, Steven; Dispenzieri, Angela

    2016-10-01

    There is no consensus on whether patients with immunoglobulin light chain amyloidosis (AL) should receive induction therapy prior to an autologous stem cell transplant (ASCT). This study investigated the relationships between baseline bone marrow plasmacytosis (BMPC), cardiac staging, and pre-transplant induction in AL patients. All patients who received ASCT for AL within 12 months of diagnosis were included. Patient characteristics and outcomes were abstracted. Univariate and multivariate modeling was performed. Among 415 AL patients, 35% had induction prior to ASCT. Post-ASCT hematologic CR plus VGPR rates were significantly higher in those with baseline BMPC ≤ 10% compared to BMPC >10% (58% versus 40%, P = 0.0013). Significant risk factors for lack of attainment of CR included attenuated dose melphalan conditioning, baseline BMPC > 10%, no induction, and male gender. The 5-year OS for the entire group was 65%. On multivariate analysis, risk factors for inferior OS included no induction therapy, advanced AL amyloid staging, BMPC > 10%, attenuated conditioning melphalan dose, and male gender. Patients with Mayo 2012 stage I-II patients with BMPC ≤ 10%, who comprised 56% of the ASCT population fared exceedingly well regardless of whether or not they received induction therapy with a 5-year OS of 81 to 83%. Induction therapy pre-ASCT may improve outcomes among AL patients due to a rapid reduction of toxic light chains or alternatively by elimination of less fit patients by "testing" their ability to tolerate chemotherapy. Prospective studies will be required to sort out these and other questions. Am. J. Hematol. 91:984-988, 2016. © 2016 Wiley Periodicals, Inc.

  2. Quality of life before autologous stem cells transplantation as prognostic factor in patients with malignant lymphomas

    Directory of Open Access Journals (Sweden)

    Yu. L. Shevchenko

    2014-07-01

    Full Text Available Currently high-doses chemotherapy (HD-PCT + autologous hematopoietic stem cells transplantation (auto-HSCT is the treatment ofchoice in patients with recurrent and progressive lymphomas. Most of quality of life (QoL studies in lymphomas patients received HSCT limited on parameters dynamics assessment in the early and late post-transplant period. Aim of this study was to evaluate the QoL parameters and their prognostic significance in lymphoma patients before transplantation. 124 patients with lymphomas (non-Hodgkin lymphomas – 45 patients, Hodgkin's lymphoma – 79 patients who received HD-PCT + auto-HSCT were included in the study: men – 42.7 % (n = 53, women – 57.3 % (n = 71, median age – 34 years (19–65 years. Patients’ heterogeneity before transplantation regarding quality of life has been revealed. Almost 1/3 of patients showed a significant reduction in the integral index of QoL. Insignificant differences between patients with chemosensitivity and chemoresistant lymphomas regarding QoL before HD-PCT + auto-HSCT were shown. We also analyzed the outcomes of studied patients received HD-PCT + auto-HSCT. With a median follow-up of 18 months, overall survival after transplantation was 72 % (95 % CI 56–84; event-free survival – 64 % (95 % CI 53,3–73,2.Overall and event-free survivals were significantly higher in patients with chemosensitive lymphoma compared with chemoresistance tumor. Differences in the survival rates between patients with no or negligible decrease of QoL integral index and with significant reduction of it also were found. Revealed differences in overall and event-free survival between the groups allowed the first group considered as patients with a favorable prognosis, and the second group – as patients with poor prognosis regarding the transplantation outcome.

  3. Autologous stem cell therapy to treat chronic ulcer in heifer- A case study

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    Jayakrushna Das

    Full Text Available Aim: The study was conducted to reveal the efficacy of Bone marrow derived mesenchymal stem cells (BM-MSCs based therapy in healing of chronic non-healing and ulcerative wound in bovine species. Materials and Methods: One 2 years old Jersey heifer affected with chronic ulcerative wound involving full thickness skin and under lying muscle at dorsal side of lumbar region since four months at the time of presentation. Bone marrow was collected from tibia, cultured and grown and after achievement of optimum confluence it was applied at the site. Different parameters of clinical, physiological, haematological, biochemical, histochemical, histological, tensile strength and photographic evaluations were done during the study period. Results: The estimated values of above mentioned parameters on zero day and after healing (18 days showed significant difference (P<0.05 in relation to collagen content, tensile strength and physical characteristics of wound like extent of wound, size of wound, type of exudates and photography. But clinical, haematological and biochemical data showed no significant difference. Conclusion: The BM-MSCs were the main pioneers to bring the chronic ulcerative wound towards healing. The procedure is simple, safe and effective in bringing out healing without showing any adverse effect on host. [Vet World 2012; 5(12.000: 771-774

  4. Bone Marrow Very Small Embryonic-Like Stem Cells: New Generation of Autologous Cell Therapy Soon Ready for Prime Time?

    Science.gov (United States)

    Smadja, David M

    2017-01-18

    Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells described in human and mouse. In this issue of Stem Cell Reviews and Reports, Shaikh and colleagues show in a valuable work that mouse bone marrow collected after 5FU treatment contains VSELs able to undergo in vitro multi-lineage differentiation into cells from all three germ layers and also in germ and hematopoietic cells. These findings are robust since no confounding factor such as feeder cell fusion with VSELs can occur here. This paper allows one to better appreciate bone marrow-VSELs differentiation potential and opens new perspectives for autologous cell therapy. Furthermore, it might help explaining lots of contradictive data from the past 20 years, in particular related to ability of bone marrow cells to differentiate into cardiomyocytes.

  5. Isolation and characterization of exosome from human embryonic stem cell-derived c-myc-immortalized mesenchymal stem cells

    NARCIS (Netherlands)

    Lai, Ruenn Chai; Yeo, Ronne Wee Yeh; Padmanabhan, Jayanthi; Choo, Andre; De Kleijn, Dominique P V; Lim, Sai Kiang

    2016-01-01

    Mesenchymal stem cells (MSC) are currently the cell type of choice in many cell therapy trials. The number of therapeutic applications for MSCs registered as product IND submissions with the FDA and initiation of registered clinical trials has increased substantially in recent years, in particular b

  6. Evaluation of transport conditions for autologous bone marrow-derived mesenchymal stromal cells for therapeutic application in horses

    Directory of Open Access Journals (Sweden)

    Miguel Espina

    2016-03-01

    Full Text Available Background. Mesenchymal stromal cells (MSCs are increasingly used for clinical applications in equine patients. For MSC isolation and expansion, a laboratory step is mandatory, after which the cells are sent back to the attending veterinarian. Preserving the biological properties of MSCs during this transport is paramount. The goal of the study was to compare transport-related parameters (transport container, media, temperature, time, cell concentration that potentially influence characteristics of culture expanded equine MSCs. Methods. The study was arranged in three parts comparing (I five different transport containers (cryotube, two types of plastic syringes, glass syringe, CellSeal, (II seven different transport media, four temperatures (4 °C vs. room temperature; −20 °C vs. −80 °C, four time frames (24 h vs. 48 h; 48 h vs. 72 h, and (III three MSC concentrations (5 × 106, 10 × 106, 20 × 106 MSC/ml. Cell viability (Trypan Blue exclusion; percent and total number viable cell, proliferation and trilineage differentiation capacity were assessed for each test condition. Further, the recovered volume of the suspension was determined in part I. Each condition was evaluated using samples of six horses (n = 6 and differentiation protocols were performed in duplicates. Results. In part I of the study, no significant differences in any of the parameters were found when comparing transport containers at room temperature. The glass syringe was selected for all subsequent evaluations (highest recoverable volume of cell suspension and cell viability. In part II, media, temperatures, or time frames had also no significant influence on cell viability, likely due to the large number of comparisons and small sample size. Highest cell viability was observed using autologous bone marrow supernatant as transport medium, and “transport” at 4 °C for 24 h (70.6% vs. control group 75.3%; this was not significant. Contrary, viability was unacceptably

  7. Treatment of Moyamoya disease by multipoint skull drilling for indirect revascularization combined with mobilization of autologous bone marrow stem cells.

    Science.gov (United States)

    Wu, R; Su, N; Zhang, Z; Jia, F

    2015-07-06

    This study discusses the clinical efficacy of multipoint skull drilling for indirect revascularization combined with mobilization of autologous bone marrow stem cells and use of simvastatin in the treatment of moyamoya disease. Seventy-eight patients [control group (group A), 39 patients; experimental group (group B), 39 patients] with moyamoya disease were selected. Group A underwent indirect revascularization, and group B, in addition to indirect revascularization, received alternate subcutaneous injections from day 7 post-surgery. The number and differentiation of the mobilized bone marrow stem cells were detected by the proportion of hematopoietic progenitor cell (HPCs) in mononuclear cells (MNCs) in the peripheral blood. There was no statistical difference in the BI (80.2 ± 13.7) and NIHSS (6.7 ± 2.3) scores between the groups before treatment (P > 0.05). The CSS score of group B was 13.5 ± 0.6 and there was a statistical significance compared to group A (18.2 ± 0.8) (P 0.05) and the proportions of CD34+ CDl33+ cells in MNCs in peripheral blood in groups A and B at 30 days after surgery were significantly higher than those before surgery (P moyamoya disease by multipoint skull drilling for indirect revascularization combined with mobilization of autologous bone marrow stem cells and simvastatin is a safe and effective method as it can promote recovery of neurological functions and improve patients' daily living abilities and quality of life.

  8. Expression of heregulin and ErbB receptors in mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    GUI Chun; WANG Jian-an; HE Ai-na; CHEN Tie-long; LIU Xian-bao; LUO Rong-hua; JIANG Jun

    2008-01-01

    Background Mesenchymal stem cells are a promising cell type for cell transplantation in myocardial infarction.Type Ⅰ neuregulins-1,also known as heregulin,can promote the survival of cardiomyocytes and stimulate angiogenesis.The purpose of this study was to investigate the expression of heregulin and ErbB receptors in mesenchymaI stem cells,then further detect the secretion of heregulin and the changes in expression of heregulin and ErbB receptors under conditions of serum deprivation and hypoxia.Methods Mesenchymal stem cells lsolated frOm bone marrow of 180 g male Sprague-Dawley rats were cultured.Passage 3 cells were detected experimentally by regular reverse transcriptase-polymerase chain reaction(RT-PCR),quantitative real time PCR and Western blotting.Results Heregulin and ErbB receptors were expressed in mesenchymal stem cells,and all three ErbB receptors mRNA expressions were significantly down-regulated by serum deprivation and hypoxia,but serum deprivation and hypoxia significantly increased the protein expression of heregulin.Serum deprivation and hypoxia more than 12 hours could induce the secretion of heregulin.Conclusions Mesenchymal stem cells can express all three ErbB receptors and heregulin.Serum deprivation and hypoxia decrease the mRNA expression of ErbB receptors,increase the expression of heregulin,and activate the secretion of heregulin.

  9. Serologic response to a 23-valent pneumococcal vaccine administered prior to autologous stem cell transplantation in patients with multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Ingels, Helene A S; Slotved, Hans-Christian;

    2012-01-01

    prior to autologous stem cell transplantation (ASCT). Specific antibody titers were measured before and after vaccination. Disease stage was evaluated and associated to the response. We found that 33% of the patients responded to the vaccine. There was a statistic significant association between...... response to the vaccine and disease stage (p = 0.01). We conclude that vaccination against S. pneumoniae prior to ASCT is reasonable at least in patients responding well to induction therapy, but still it is important to be aware that the response is frequently poor and the duration of it is unknown....

  10. Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition.

    Science.gov (United States)

    Espinoza, Ingrid; Pochampally, Radhika; Xing, Fei; Watabe, Kounosuke; Miele, Lucio

    2013-09-06

    Notch signaling is an evolutionarily conserved pathway involved in cell fate control during development, stem cell self-renewal, and postnatal tissue differentiation. Roles for Notch in carcinogenesis, the biology of cancer stem cells, tumor angiogenesis, and epithelial-to-mesenchymal transition (EMT) have been reported. This review describes the role of Notch in the "stemness" program in cancer cells and in metastases, together with a brief update on the Notch inhibitors currently under investigation in oncology. These agents may be useful in targeting cancer stem cells and to reverse the EMT process.

  11. Mesenchymal and embryonic characteristics of stem cells obtained from mouse dental pulp

    DEFF Research Database (Denmark)

    Guimarães, Elisalva Teixeira; Cruz, Gabriela Silva; de Jesus, Alan Araújo

    2011-01-01

    OBJECTIVE: Several studies have demonstrated that human dental pulp is a source of mesenchymal stem cells. To better understand the biological properties of these cells we isolated and characterized stem cells from the dental pulp of EGFP transgenic mice. METHODS: The pulp tissue was gently...... is an important source of adult stem cells and encourage studies on therapeutic potential of mDPSC in experimental disease models....... separated from the roots of teeth extracted from C57BL/6 mice, and cultured under appropriate conditions. Flow cytometry, RT-PCR, light microscopy (staining for alkaline phosphatase) and immunofluorescence were used to investigate the expression of stem cell markers. The presence of chromosomal...

  12. Tenogenically induced allogeneic mesenchymal stem cells for the treatment of proximal suspensory ligament desmitis in a horse

    Directory of Open Access Journals (Sweden)

    Aurelie eVandenberghe

    2015-10-01

    Full Text Available Suspensory ligament injuries are a common injury in sport horses, especially in competing dressage horses. Because of the poor healing of chronic recalcitrant tendon injuries, this represents a major problem in the rehabilitation of sport horses and often compromises the return to the initial performance level. Stem cells are considered as a novel treatment for different pathologies in horses and humans. Autologous mesenchymal stem cells (MSCs are well known for their use in the treatment of tendinopathies, however, recent studies report a safe use of allogeneic MSCs for different orthopaedic applications in horses. Moreover, it has been reported that predifferentiation of MSCs prior to injection might result in improved clinical outcomes. For all these reasons, the present case report describes the use of allogeneic tenogenically induced peripheral blood-derived MSCs for the treatment of a proximal suspensory ligament injury. During conservative management for 4 months, the horse demonstrated no improvement of a right front lameness with a Grade 2/5 on the AAEP scale and a clear hypo-echoic area detectable in 30% of the cross sectional area. From 4 weeks after treatment, the lameness reduced to an AAEP Grade 1/5 and a clear filling of the lesion could be noticed on ultrasound. At 12 weeks (T4 after the first injection, a second intralesional injection with allogeneic tenogenically induced MSCs and PRP was given and at 4 weeks after the second injection (T5, the horse trotted sound under all circumstances with a close to total fiber alignment. The horse went back to previous performance level at 32 weeks after the first regenerative therapy and is currently still doing so (i.e. 20 weeks later or 1 year after the first stem cell treatment.In conclusion, the present case report demonstrated a positive evolution of proximal suspensory ligament desmitis after treatment with allogeneic tenogenically induced MSCs.

  13. Autism Spectrum Disorders: Is Mesenchymal Stem Cell Personalized Therapy the Future?

    Directory of Open Access Journals (Sweden)

    Dario Siniscalco

    2012-01-01

    Full Text Available Autism and autism spectrum disorders (ASDs are heterogeneous neurodevelopmental disorders. They are enigmatic conditions that have their origins in the interaction of genes and environmental factors. ASDs are characterized by dysfunctions in social interaction and communication skills, in addition to repetitive and stereotypic verbal and nonverbal behaviours. Immune dysfunction has been confirmed with autistic children. There are no defined mechanisms of pathogenesis or curative therapy presently available. Indeed, ASDs are still untreatable. Available treatments for autism can be divided into behavioural, nutritional, and medical approaches, although no defined standard approach exists. Nowadays, stem cell therapy represents the great promise for the future of molecular medicine. Among the stem cell population, mesenchymal stem cells (MSCs show probably best potential good results in medical research. Due to the particular immune and neural dysregulation observed in ASDs, mesenchymal stem cell transplantation could offer a unique tool to provide better resolution for this disease.

  14. Comparative analysis of mesenchymal stem cells from adult mouse adipose, muscle, and fetal muscle.

    Science.gov (United States)

    Lei, Hulong; Yu, Bing; Huang, Zhiqing; Yang, Xuerong; Liu, Zehui; Mao, Xiangbing; Tian, Gang; He, Jun; Han, Guoquan; Chen, Hong; Mao, Qian; Chen, Daiwen

    2013-02-01

    Recently, increasing evidence supports that adult stem cells are the part of a natural system for tissue growth and repair. This study focused on the differences of mesenchymal stem cells from adult adipose (ADSCs), skeletal muscle (MDSCs) and fetal muscle (FMSCs) in biological characteristics, which is the key to cell therapy success. Stem cell antigen 1 (Sca-1) expression of MDSCs and FMSCs at passage 3 was two times more than that at passage 1 (P cells (P fetal muscle expressed higher OCN and OPN than ADSCs after 28 days osteogenic induction (P cell source and developmental stage had great impacts on biological properties of mesenchymal stem cells, and proper consideration of all the issues is necessary.

  15. Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells

    DEFF Research Database (Denmark)

    Weilner, Sylvia; Schraml, Elisabeth; Wieser, Matthias

    2016-01-01

    Damage to cells and tissues is one of the driving forces of aging and age-related diseases. Various repair systems are in place to counteract this functional decline. In particular, the property of adult stem cells to self-renew and differentiate is essential for tissue homeostasis and regeneration....... However, their functionality declines with age (Rando, 2006). One organ that is notably affected by the reduced differentiation capacity of stem cells with age is the skeleton. Here, we found that circulating microvesicles impact on the osteogenic differentiation capacity of mesenchymal stem cells....... As a potential source of its secretion, we identified senescent endothelial cells, which are known to increase during aging in vivo (Erusalimsky, 2009). Endothelial miR-31 is secreted within senescent cell-derived microvesicles and taken up by mesenchymal stem cells where it inhibits osteogenic differentiation...

  16. Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction

    Science.gov (United States)

    Dufrane, Denis; Docquier, Pierre-Louis; Delloye, Christian; Poirel, Hélène A.; André, Wivine; Aouassar, Najima

    2015-01-01

    Abstract Long bone nonunion in the context of congenital pseudarthrosis or carcinologic resection (with intercalary bone allograft implantation) is one of the most challenging pathologies in pediatric orthopedics. Autologous cancellous bone remains the gold standard in this context of long bone nonunion reconstruction, but with several clinical limitations. We then assessed the feasibility and safety of human autologous scaffold-free osteogenic 3-dimensional (3D) graft (derived from autologous adipose-derived stem cells [ASCs]) to cure a bone nonunion in extreme clinical and pathophysiological conditions. Human ASCs (obtained from subcutaneous adipose tissue of 6 patients and expanded up to passage 4) were incubated in osteogenic media and supplemented with demineralized bone matrix to obtain the scaffold-free 3D osteogenic structure as confirmed in vitro by histomorphometry for osteogenesis and mineralization. The 3D “bone-like” structure was finally transplanted for 3 patients with bone tumor and 3 patients with bone pseudarthrosis (2 congenital, 1 acquired) to assess the clinical feasibility, safety, and efficacy. Although minor clones with structural aberrations (aneuploidies, such as tri or tetraploidies or clonal trisomy 7 in 6%–20% of cells) were detected in the undifferentiated ASCs at passage 4, the osteogenic differentiation significantly reduced these clonal anomalies. The final osteogenic product was stable, did not rupture with forceps manipulation, did not induce donor site morbidity, and was easily implanted directly into the bone defect. No acute (development, were associated with the graft up to 4 years after transplantation. We report for the first time that autologous ASC can be fully differentiated into a 3D osteogenic-like implant without any scaffold. We demonstrated that this engineered tissue can safely promote osteogenesis in extreme conditions of bone nonunions with minor donor site morbidity and no oncological side effects. PMID

  17. Exosome: A Novel and Safer Therapeutic Refinement of Mesenchymal Stem Cell

    OpenAIRE

    Yeo, Ronne Wee Yeh; Lai, Ruenn Chai; Tan, Kok Hian; Lim, Sai Kiang

    2013-01-01

    Mesenchymal stem cell (MSC) has just been approved as the first “off-the-shelf” stem cell pharmaceutical drug with an anticipation of more approvals following completion of numerous rigorous clinical trials. Despite this progress, the rationale for MSC therapeutic efficacy remains tenuous and is increasingly rationalized on a secretion rather than differentiation mechanism. Recent studies identifying exosome as the secreted agent mediating MSC therapeutic efficacy coul...

  18. The clinical application of mesenchymal stromal cells in hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Ke Zhao

    2016-05-01

    Full Text Available Abstract Mesenchymal stromal cells (MSCs are multipotent stem cells well known for repairing tissue, supporting hematopoiesis, and modulating immune and inflammation response. These outstanding properties make MSCs as an attractive candidate for cellular therapy in immune-based disorders, especially hematopoietic stem cell transplantation (HSCT. In this review, we outline the progress of MSCs in preventing and treating engraftment failure (EF, graft-versus-host disease (GVHD following HSCT and critically discuss unsolved issues in clinical applications.

  19. The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds

    OpenAIRE

    Kim, Ju-Won; Lee, Jong-Hwan; Lyoo, Young S.; JUNG, Dong-In; Park, Hee-Myung

    2013-01-01

    Background Adult stem cells have been widely investigated in bioengineering approaches for tissue repair therapy. We evaluated the clinical value and safety of the application of cultured bone marrow-derived allogenic mesenchymal stem cells (MSCs) for treating skin wounds in a canine model. Hypothesis Topical allogenic MSC transplantation can accelerate the closure of experimental full-thickness cutaneous wounds and attenuate local inflammation. Animals Adult healthy beagle dogs (n = 10; 3–6 ...

  20. Osteogenesis of peripheral blood mesenchymal stem cells in self assembling peptide nanofiber for healing critical size calvarial bony defect

    Science.gov (United States)

    Wu, Guofeng; Pan, Mengjie; Wang, Xianghai; Wen, Jinkun; Cao, Shangtao; Li, Zhenlin; Li, Yuanyuan; Qian, Changhui; Liu, Zhongying; Wu, Wutian; Zhu, Lixin; Guo, Jiasong

    2015-01-01

    Peripheral blood mesenchymal stem cells (PBMSCs) may be easily harvested from patients, permitting autologous grafts for bone tissue engineering in the future. However, the PBMSC’s capabilities of survival, osteogenesis and production of new bone matrix in the defect area are still unclear. Herein, PBMSCs were seeded into a nanofiber scaffold of self-assembling peptide (SAP) and cultured in osteogenic medium. The results indicated SAP can serve as a promising scaffold for PBMSCs survival and osteogenic differentiation in 3D conditions. Furthermore, the SAP seeded with the induced PBMSCs was splinted by two membranes of poly(lactic)-glycolic acid (PLGA) to fabricate a composited scaffold which was then used to repair a critical-size calvarial bone defect model in rat. Twelve weeks later the defect healing and mineralization were assessed by H&E staining and microcomputerized tomography (micro-CT). The osteogenesis and new bone formation of grafted cells in the scaffold were evaluated by immunohistochemistry. To our knowledge this is the first report with solid evidence demonstrating PBMSCs can survive in the bone defect area and directly contribute to new bone formation. Moreover, the present data also indicated the tissue engineering with PBMSCs/SAP/PLGA scaffold can serve as a novel prospective strategy for healing large size cranial defects. PMID:26568114

  1. Standard requirement of a microbiological quality control program for the manufacture of human mesenchymal stem cells for clinical use.

    Science.gov (United States)

    Gálvez, Patricia; Clares, Beatriz; Bermejo, Maria; Hmadcha, Abdelkrim; Soria, Bernat

    2014-05-15

    The manufacturing of human mesenchymal stem cells (hMSCs) as cell-based products for clinical use should be performed with appropriate controls that ensure its safety and quality. The use of hMSCs in cell therapy has increased considerably in the past few years. In line with this, the assessment and management of contamination risks by microbial agents that could affect the quality of cells and the safety of patients have to be considered. It is necessary to implant a quality control program (QCP) covering the entire procedure of the ex vivo expansion, from the source of cells, starting materials, and reagents, such as intermediate products, to the final cellular medicine. We defined a QCP to detect microbiological contamination during manufacturing of autologous hMSCs for clinical application. The methods used include sterility test, Gram stain, detection of mycoplasma, endotoxin assay, and microbiological monitoring in process according to the European Pharmacopoeia (Ph. Eur.) and each analytical technique was validated in accordance with three different cell cultures. Results showed no microbiological contamination in any phases of the cultures, meeting all the acceptance criteria for sterility test, detection of mycoplasma and endotoxin, and environmental and staff monitoring. Each analytical technique was validated demonstrating the sensitivity, limit of detection, and robustness of the method. The quality and safety of MSCs must be controlled to ensure their final use in patients. The evaluation of the proposed QCP revealed satisfactory results in order to standardize this procedure for clinical use of cells.

  2. TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells.

    Science.gov (United States)

    Moniri, M R; Sun, X-Y; Rayat, J; Dai, D; Ao, Z; He, Z; Verchere, C B; Dai, L-J; Warnock, G L

    2012-09-01

    Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy owing to their tumor-oriented homing capacity and the feasibility of autologous transplantation. Currently, pancreatic cancer patients face a very poor prognosis, primarily due to the lack of therapeutic strategies with an effective degree of specificity. Anticancer gene-engineered MSCs specifically target tumor sites and can produce anticancer agents locally and constantly. This study was performed to characterize pancreas-derived MSCs and investigate the effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on pancreatic cancer cells under different culture conditions. Pancreas-derived MSCs exhibited positive expression on CD44, CD73, CD95, CD105, negative on CD34 and differentiated into adipogenic and osteogenic cells. TRAIL expression was assessed by both enzyme-linked immunosorbent assay and western blot analysis. Different patterns of TRAIL receptor expression were observed on the pancreatic cancer cell lines, including PANC1, HP62, ASPC1, TRM6 and BXPC3. Cell viability was assessed using a real-time monitoring system. Pancreatic cancer cell death was proportionally related to conditioned media from MSC(nsTRAIL) and MSC(stTRAIL). The results suggest that MSCs exhibit intrinsic inhibition of pancreatic cancer cells and that this effect can be potentiated by TRAIL-transfection on death receptor-bearing cell types.

  3. Influence of mesenchymal stem cells on the response of endothelial cells to laminar flow and shear stress.

    Science.gov (United States)

    Hong, Minsung; Jo, Hansu; Ankeny, Randell F; Holliday-Ankeny, Casey J; Kim, Hyengseok; Khang, Gilson; Nerem, Robert M

    2013-01-01

    The interactions between endothelial cells (ECs) and smooth muscle cells (SMCs) in a complex hemodynamic environment play an important role in the control of blood vessel function. Since autologous SMCs are not readily available for the tissue engineering of a blood vessel substitute, a substitute for SMCs, such as human adult bone marrow-derived mesenchymal stem cells (MSCs), is needed. The objective of this study was to use a three-dimensional coculture model of the blood vessel wall, comprised of ECs and MSCs, to determine how the presence of MSCs affects EC function. Two vascular coculture models with an EC monolayer were created using type I collagen. All models were exposed to steady laminar flow with a shear stress of 15 dyn/cm(2) for up to 48 h. ECs in both the MSC and SMC coculture models expressed up-regulated EC-specific markers compared to the EC-only control model. The most dramatic difference observed between the two coculture models was in the experiments assessing monocyte adhesion. Here, fewer monocytes bound after laminar shear compared to static conditions; however, the number of bound monocytes was much lower for the EC-MSC coculture model than the EC-SMC coculture model for both static and shear conditions. These results suggest the feasibility of developing a tissue-engineered blood vessel substitute using MSCs as a substitute for SMCs.

  4. Conditioned medium of periodontal ligament mesenchymal stem cells exert anti-inflammatory effects in lipopolysaccharide-activated mouse motoneurons.

    Science.gov (United States)

    Rajan, Thangavelu Soundara; Giacoppo, Sabrina; Trubiani, Oriana; Diomede, Francesca; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela

    2016-11-15

    Conditioned medium derived from mesenchymal stem cells (MSCs) shows immunomodulatory and neuroprotective effects in preclinical models. Given the difficulty to harvest MSCs from bone marrow and adipose tissues, research has been focused to find alternative resources for MSCs, such as oral-derived tissues. Recently, we have demonstrated the protective effects of MSCs obtained from healthy human periodontal ligament tissue (hPDLSCs) in murine experimental autoimmune encephalomyelitis model. In the present in vitro study, we have investigated the immunomodulatory and neuroprotective effects of conditioned medium obtained from hPDLSCs of Relapsing Remitting- Multiple sclerosis (RR-MS) patients on NSC34 mouse motoneurons stimulated with lipopolysaccharide (LPS). Immunocytochemistry and western blotting were performed. Increased level of TLR4 and NFκB, and reduced level of IκB-α were observed in LPS-stimulated motoneurons, which were modulated by pre-conditioning with hPDLSC-conditioned medium. Inflammatory cytokines (TNF-α, IL-10), neuroprotective markers (Nestin, NFL 70, NGF, GAP43), and apoptotic markers (Bax, Bcl-2, p21) were modulated. Moreover, extracellular vesicles of hPDLSC-conditioned medium showed the presence of anti-inflammatory cytokines IL-10 and TGF-β. Our results demonstrate the immunosuppressive properties of hPDLSC-conditioned medium of RR-MS patients in motoneurons subjected to inflammation. Our findings warrant further preclinical and clinical studies to elucidate the autologous therapeutic efficacy of hPDLSC-conditioned medium in neurodegenerative diseases.

  5. Platelet-released supernatant induces osteoblastic differentiation of human mesenchymal stem cells: potential role of BMP-2

    Directory of Open Access Journals (Sweden)

    M Alini

    2010-12-01

    Full Text Available Platelet-rich preparations have recently gained popularity in maxillofacial and dental surgery, but their beneficial effect is still under debate. Furthermore, very little is known about the effect of platelet preparations at the cellular level, and the underlying mechanisms. In this study, we tested the effect of platelet-released supernatant (PRS on human mesenchymal stem cell (MSC differentiation towards an osteoblastic phenotype in vitro. Cultures of MSC were supplemented with PRS and typical osteoblastic markers were assessed at up to 28 days post-confluence. PRS showed an osteoinductive effect on MSC, as shown by an increased expression of typical osteoblastic marker genes such as collagen Ialpha1, bone sialoprotein II, BMP-2 and MMP-13, as well as by increased 45Ca2+ incorporation. Our results suggest that the effect of PRS on human MSC could be at least partially mediated by BMP-2.Activated autologous PRS could therefore provide an alternative to agents like recombinant bone growth factors by increasing osteoblastic differentiation of bone precursor cells at bone repair sites, although further studies are needed to fully support our observations.

  6. Mesenchymal stem cells to treat diabetic neuropathy: a long and strenuous way from bench to the clinic.

    Science.gov (United States)

    Zhou, J Y; Zhang, Z; Qian, G S

    2016-01-01

    As one of the most common complications of diabetes, diabetic neuropathy often causes foot ulcers and even limb amputations. Inspite of continuous development in antidiabetic drugs, there is still no efficient therapy to cure diabetic neuropathy. Diabetic neuropathy shows declined vascularity in peripheral nerves and lack of angiogenic and neurotrophic factors. Mesenchymal stem cells (MSCs) have been indicated as a novel emerging regenerative therapy for diabetic neuropathy because of their multipotency. We will briefly review the pathogenesis of diabetic neuropathy, characteristic of MSCs, effects of MSC therapies for diabetic neuropathy and its related mechanisms. In order to treat diabetic neuropathy, neurotrophic or angiogenic factors in the form of protein or gene therapy are delivered to diabetic neuropathy, but therapeutic efficiencies are very modest if not ineffective. MSC treatment reverses manifestations of diabetic neuropathy. MSCs have an important role to repair tissue and to lower blood glucose level. MSCs even paracrinely secrete neurotrophic factors, angiogenic factors, cytokines, and immunomodulatory substances to ameliorate diabetic neuropathy. There are still several challenges in the clinical translation of MSC therapy, such as safety, optimal dose of administration, optimal mode of cell delivery, issues of MSC heterogeneity, clinically meaningful engraftment, autologous or allogeneic approach, challenges with cell manufacture, and further mechanisms.

  7. Isolation, Culture, Differentiation, and Nuclear Reprogramming of Mongolian Sheep Fetal Bone Marrow-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Su, Xiaohu; Ling, Yu; Liu, Chunxia; Meng, Fanhua; Cao, Junwei; Zhang, Li; Zhou, Huanmin; Liu, Zongzheng; Zhang, Yanru

    2015-08-01

    We have characterized the differentiation potentiality and the developmental potential of cloned embryos of fetal bone marrow mesenchymal stem cells (BMSCs) isolated from Mongolian sheep. BMSCs were harvested by centrifuging after the explants method and the mononuclear cells obtained were cultured. The isolated BMSCs were uniform, with a fibroblast-like spindle or stellate appearance, and we confirmed expression of OCT4, SOX2, and NANOG genes at passage 3 (P3) by RT-PCR. We measured the growth of the passage 1, 5, and 10 cultures and found exponential growth with a population doubling time of 29.7±0.05 h. We cultured the P3 BMSCs in vitro under inductive environments and were able to induce them to undergo neurogenesis and form cardiomyocytes and adipocytes. Donor cells at passages 3-4 were used for nuclear transfer (NT). We found the BMSCs could be expanded in vitro and used as nuclear donors for somatic cell nuclear transfer (SCNT). Thus, BMSCs are an attractive cell type for large-animal autologous studies and will be valuable material for somatic cell cloning and future transgenic research.

  8. Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration.

    Science.gov (United States)

    Jung, Namhee; Park, Saeyoung; Choi, Yoonyoung; Park, Joo-Won; Hong, Young Bin; Park, Hyun Ho Choi; Yu, Yeonsil; Kwak, Geon; Kim, Han Su; Ryu, Kyung-Ha; Kim, Jae Kwang; Jo, Inho; Choi, Byung-Ok; Jung, Sung-Chul

    2016-11-09

    Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been performed and has shown promising clinical results for treating nerve injuries and donor site morbidity, and insufficient production of the cells have been considered as a major issue. Here, we performed differentiation of tonsil-derived mesenchymal stem cells (T-MSCs) into SC-like cells (T-MSC-SCs), to evaluate T-MSC-SCs as an alternative to SCs. Using SC markers such as CAD19, GFAP, MBP, NGFR, S100B, and KROX20 during quantitative real-time PCR we detected the upregulation of NGFR, S100B, and KROX20 and the downregulation of CAD19 and MBP at the fully differentiated stage. Furthermore, we found myelination of axons when differentiated SCs were cocultured with mouse dorsal root ganglion neurons. The application of T-MSC-SCs to a mouse model of sciatic nerve injury produced marked improvements in gait and promoted regeneration of damaged nerves. Thus, the transplantation of human T-MSCs might be suitable for assisting in peripheral nerve regeneration.

  9. Advances in mesenchymal stem cell-based strategies for cartilage repair and regeneration.

    Science.gov (United States)

    Toh, Wei Seong; Foldager, Casper Bindzus; Pei, Ming; Hui, James Hoi Po

    2014-10-01

    Significant research efforts have been undertaken in the last decade in the development of stem cell-based therapies for cartilage repair. Among the various stem cell sources, mesenchymal stem cells (MSCs) demonstrate great promise and clinical efficacy in cartilage regeneration. With a deeper understanding of stem cell biology, new therapeutics and new bioengineering approaches have emerged and showed potential for further developments. Of note, there has been a paradigm shift in applying MSCs for tissue regeneration from the use of stem cells for transplantation to the use of stem cell-derived matrix and secretome components as therapeutic tools and agents for cartilage regeneration. In this review, we will discuss the emerging role of MSCs in cartilage regeneration and the most recent advances in development of stem cell-based therapeutics for cartilage regeneration.

  10. Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth

    Directory of Open Access Journals (Sweden)

    Maria E. Gonzalez

    2017-01-01

    Full Text Available Increased collagen deposition by breast cancer (BC-associated mesenchymal stem/multipotent stromal cells (MSC promotes metastasis, but the mechanisms are unknown. Here, we report that the collagen receptor discoidin domain receptor 2 (DDR2 is essential for stromal-BC communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. In MSCs isolated from human BC metastasis, DDR2 maintains a fibroblastic phenotype with collagen deposition and induces pathological activation of DDR2 signaling in BC cells. Loss of DDR2 in MSCs impairs their ability to promote DDR2 phosphorylation in BC cells, as well as BC cell alignment, migration, and metastasis. Female ddr2-deficient mice homozygous for the slie mutation show inefficient spontaneous BC metastasis. These results point to a role for mesenchymal stem cell DDR2 in metastasis and suggest a therapeutic approach for metastatic BC.

  11. Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth.

    Science.gov (United States)

    Gonzalez, Maria E; Martin, Emily E; Anwar, Talha; Arellano-Garcia, Caroline; Medhora, Natasha; Lama, Arjun; Chen, Yu-Chih; Tanager, Kevin S; Yoon, Euisik; Kidwell, Kelley M; Ge, Chunxi; Franceschi, Renny T; Kleer, Celina G

    2017-01-31

    Increased collagen deposition by breast cancer (BC)-associated mesenchymal stem/multipotent stromal cells (MSC) promotes metastasis, but the mechanisms are unknown. Here, we report that the collagen receptor discoidin domain receptor 2 (DDR2) is essential for stromal-BC communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. In MSCs isolated from human BC metastasis, DDR2 maintains a fibroblastic phenotype with collagen deposition and induces pathological activation of DDR2 signaling in BC cells. Loss of DDR2 in MSCs impairs their ability to promote DDR2 phosphorylation in BC cells, as well as BC cell alignment, migration, and metastasis. Female ddr2-deficient mice homozygous for the slie mutation show inefficient spontaneous BC metastasis. These results point to a role for mesenchymal stem cell DDR2 in metastasis and suggest a therapeutic approach for metastatic BC.

  12. Flow perfusion culture of human mesenchymal stem cells on coralline hydroxyapatite scaffolds with various pore sizes.

    Science.gov (United States)

    Bjerre, Lea; Bünger, Cody; Baatrup, Anette; Kassem, Moustapha; Mygind, Tina

    2011-06-01

    Bone grafts are widely used in orthopaedic reconstructive surgery, but harvesting of autologous grafts is limited due to donor site complications. Bone tissue engineering is a possible alternative source for substitutes, and to date, mainly small scaffold sizes have been evaluated. The aim of this study was to obtain a clinically relevant substitute size using a direct perfusion culture system. Human bone marrowderived mesenchymal stem cells were seeded on coralline hydroxyapatite scaffolds with 200 μm or 500 μm pores, and resulting constructs were cultured in a perfusion bioreactor or in static culture for up to 21 days and analysed for cell distribution and osteogenic differentiation using histological stainings, alkaline phosphatase activity assay, and real-time RT-PCR on bone markers. We found that the number of cells was higher during static culture at most time points and that the final number of cells was higher in 500 μm constructs as compared with 200 μm constructs. Alkaline phosphatase enzyme activity assays and real time RT-PCR on seven osteogenic markers showed that differentiation occurred primarily and earlier in statically cultured constructs with 200 μm pores compared with 500 μm ones. Adhesion and proliferation of the cells was seen on both scaffold sizes, but the vitality and morphology of cells changed unfavorably during perfusion culture. In contrast to previous studies using spinner flask that show increased cellularity and osteogenic properties of cells when cultured dynamically, the perfusion culture in our study did not enhance the osteogenic properties of cell/scaffold constructs. The statically cultured constructs showed increasing cell numbers and abundant osteogenic differentiation probably because of weak initial cell adhesion due to the surface morphology of scaffolds. Our conclusion is that the specific scaffold surface microstructure and culturing system flow dynamics has a great impact on cell distribution and proliferation

  13. In vitro mesenchymal stem cell response to a CO{sub 2} laser modified polymeric material

    Energy Technology Data Exchange (ETDEWEB)

    Waugh, D.G., E-mail: d.waugh@chester.ac.uk [Laser Engineering and Manufacturing Research Centre, Faculty of Science and Engineering, University of Chester, Chester CH1 4BJ (United Kingdom); Hussain, I. [School of Life Sciences, Brayford Pool, University of Lincoln, Lincoln LN6 7TS (United Kingdom); Lawrence, J.; Smith, G.C. [Laser Engineering and Manufacturing Research Centre, Faculty of Science and Engineering, University of Chester, Chester CH1 4BJ (United Kingdom); Cosgrove, D. [School of Life Sciences, Brayford Pool, University of Lincoln, Lincoln LN6 7TS (United Kingdom); Toccaceli, C. [Laser Engineering and Manufacturing Research Centre, Faculty of Science and Engineering, University of Chester, Chester CH1 4BJ (United Kingdom)

    2016-10-01

    With an ageing world population it is becoming significantly apparent that there is a need to produce implants and platforms to manipulate stem cell growth on a pharmaceutical scale. This is needed to meet the socio-economic demands of many countries worldwide. This paper details one of the first ever studies in to the manipulation of stem cell growth on CO{sub 2} laser surface treated nylon 6,6 highlighting its potential as an inexpensive platform to manipulate stem cell growth on a pharmaceutical scale. Through CO{sub 2} laser surface treatment discrete changes to the surfaces were made. That is, the surface roughness of the nylon 6,6 was increased by up to 4.3 μm, the contact angle was modulated by up to 5° and the surface oxygen content increased by up to 1 atom %. Following mesenchymal stem cell growth on the laser treated samples, it was identified that CO{sub 2} laser surface treatment gave rise to an enhanced response with an increase in viable cell count of up to 60,000 cells/ml when compared to the as-received sample. The effect of surface parameters modified by the CO{sub 2} laser surface treatment on the mesenchymal stem cell response is also discussed along with potential trends that could be identified to govern the mesenchymal stem cell response.

  14. In vitro mesenchymal stem cell response to a CO2 laser modified polymeric material.

    Science.gov (United States)

    Waugh, D G; Hussain, I; Lawrence, J; Smith, G C; Cosgrove, D; Toccaceli, C

    2016-10-01

    With an ageing world population it is becoming significantly apparent that there is a need to produce implants and platforms to manipulate stem cell growth on a pharmaceutical scale. This is needed to meet the socio-economic demands of many countries worldwide. This paper details one of the first ever studies in to the manipulation of stem cell growth on CO2 laser surface treated nylon 6,6 highlighting its potential as an inexpensive platform to manipulate stem cell growth on a pharmaceutical scale. Through CO2 laser surface treatment discrete changes to the surfaces were made. That is, the surface roughness of the nylon 6,6 was increased by up to 4.3μm, the contact angle was modulated by up to 5° and the surface oxygen content increased by up to 1atom %. Following mesenchymal stem cell growth on the laser treated samples, it was identified that CO2 laser surface treatment gave rise to an enhanced response with an increase in viable cell count of up to 60,000cells/ml when compared to the as-received sample. The effect of surface parameters modified by the CO2 laser surface treatment on the mesenchymal stem cell response is also discussed along with potential trends that could be identified to govern the mesenchymal stem cell response.

  15. Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Christopher Dravis

    2015-09-01

    Full Text Available To discover mechanisms that mediate plasticity in mammary cells, we characterized signaling networks that are present in the mammary stem cells responsible for fetal and adult mammary development. These analyses identified a signaling axis between FGF signaling and the transcription factor Sox10. Here, we show that Sox10 is specifically expressed in mammary cells exhibiting the highest levels of stem/progenitor activity. This includes fetal and adult mammary cells in vivo and mammary organoids in vitro. Sox10 is functionally relevant, as its deletion reduces stem/progenitor competence whereas its overexpression increases stem/progenitor activity. Intriguingly, we also show that Sox10 overexpression causes mammary cells to undergo a mesenchymal transition. Consistent with these findings, Sox10 is preferentially expressed in stem- and mesenchymal-like breast cancers. These results demonstrate a signaling mechanism through which stem and mesenchymal states are acquired in mammary cells and suggest therapeutic avenues in breast cancers for which targeted therapies are currently unavailable.

  16. Mesenchymal stem cells maintain TGF-beta-mediated chondrogenic phenotype in alginate bead culture

    DEFF Research Database (Denmark)

    Mehlhorn, A T; Schmal, H; Kaiser, S

    2006-01-01

    This article addresses the stability of chondrogenic phenotype and the transdifferentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) at distinct stages of differentiation. Differentiated MSCs were expected to maintain cartilage-like gene expression pattern in the absence of ...

  17. MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo

    DEFF Research Database (Denmark)

    Eskildsen, Tilde; Taipaleenmäki, H.; Stenvang, Jan;

    2011-01-01

    Elucidating the molecular mechanisms that regulate human stromal (mesenchymal) stem cell (hMSC) differentiation into osteogenic lineage is important for the development of anabolic therapies for treatment of osteoporosis. MicroRNAs (miRNAs) are short, noncoding RNAs that act as key regulators...

  18. Enhanced adipogenic differentiation of bovine bone marrow-derived mesenchymal stem cells

    Science.gov (United States)

    Until now, the isolation and characterization of bovine bone marrow-derived mesenchymal stem cells (bBM-MSCs) have not been established, which prompted us to optimize the differentiation protocol for bBM-MSCs. In this study, bBM-MSCs were freshly isolated from three 6-month-old cattle and used for p...

  19. Oxymatrine could promote mesenchymal stem cell therapy in hepatic fibrosis rats:an experimental research

    Institute of Scientific and Technical Information of China (English)

    柴宁莉

    2013-01-01

    Objective To investigate whether oxymatrine (OM) could promote mesenchymal stem cell (MSC) therapy in CCl4-induced hepatic fibrosis (HF) in rats and to initially explore its mechanisms.Methods Totally 50 male SD rats were randomly divided into five groups,i.e.,nor-

  20. Human bone marrow mesenchymal stem cell transplantation attenuates axonal injur y in stroke rats

    Institute of Scientific and Technical Information of China (English)

    Yi Xu; Shiwei Du; Xinguang Yu; Xiao Han; Jincai Hou; Hao Guo

    2014-01-01

    Previous studies have shown that transplantation of human bone marrow mesenchymal stem cells promotes neural functional recovery after stroke, but the neurorestorative mechanisms remain largely unknown. We hypothesized that functional recovery of myelinated axons may be one of underlying mechanisms. In this study, an ischemia/reperfusion rat model was established using the middle cerebral artery occlusion method. Rats were used to test the hypothesis that in-travenous transplantation of human bone marrow mesenchymal stem cells through the femoral vein could exert neuroprotective effects against cerebral ischemia via a mechanism associated with the ability to attenuate axonal injury. The results of behavioral tests, infarction volume analysis and immunohistochemistry showed that cerebral ischemia caused severe damage to the myelin sheath and axons. After rats were intravenously transplanted with human bone marrow mesenchymal stem cells, the levels of axon and myelin sheath-related proteins, including mi-crotubule-associated protein 2, myelin basic protein, and growth-associated protein 43, were elevated, infarct volume was decreased and neural function was improved in cerebral ischemic rats. These ifndings suggest that intravenously transplanted human bone marrow mesenchymal stem cells promote neural function. Possible mechanisms underlying these beneifcial effects in-clude resistance to demyelination after cerebral ischemia, prevention of axonal degeneration, and promotion of axonal regeneration.

  1. Mesenchymal Stem Cell Therapy for Protection and Repair of Injured Vital Organs

    NARCIS (Netherlands)

    van Poll, D.; Parekkadan, B.; Rinkes, I. H. M. Borel; Tilles, A. W.; Yarmush, M. L.

    2008-01-01

    Recently there has been a paradigm shift in what is considered to be the therapeutic promise of mesenchymal stem cells (MSCs) in diseases of vital organs. Originally, research focused on MSCs as a source of regenerative cells by differentiation of transplanted cells into lost cell types. It is now c

  2. Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells

    NARCIS (Netherlands)

    M.J. Crop (Meindert); C.C. Baan (Carla); S.S. Korevaar (Sander); J.N.M. IJzermans (Jan); M. Pescatori (Mario); A. Stubbs (Andrew); W.F.J. van IJcken (Wilfred); M.H. Dahlke (Marc); E. Eggenhofer (Elke); W. Weimar (Willem); M.J. Hoogduijn (Martin)

    2010-01-01

    textabstractThere is emerging interest in the application of mesenchymal stem cells (MSC) for the prevention and treatment of autoimmune diseases, graft-versus-host disease and allograft rejection. It is, however, unknown how inflammatory conditions affect phenotype and function of MSC. Adipose tiss

  3. Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cells

    NARCIS (Netherlands)

    Frobel, Joana; Hemeda, Hatim; Lenz, Michael; Abagnale, Giulio; Joussen, Sylvia; Denecke, Bernd; Sarić, Tomo; Zenke, Martin; Wagner, Wolfgang

    2014-01-01

    Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate toward a ground stat

  4. 2012478 Biological characteristics of bone marrow mesenchymal stem cells and JAK2 mutation in myeloproliferative neoplasms

    Institute of Scientific and Technical Information of China (English)

    田竑

    2012-01-01

    Objective To study the biological characteristics of bone marrow mesenchymal stem cells(BMSCs) and detect JAK2 mutation in BMSCs from myeloproliferative neoplasms(MPN) patients. Methods JAK2 V617F mutation and exon 12 mutation in 70 MPN patients’ blood or bone marrow samples were detected.

  5. 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

  6. 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

  7. Recent advances in mesenchymal stem cell immunomodulation: the role of microvesicles.

    Science.gov (United States)

    Fierabracci, Alessandra; Del Fattore, Andrea; Luciano, Rosa; Muraca, Marta; Teti, Anna; Muraca, Maurizio

    2015-01-01

    Mesenchymal stem cells are the most widely used cell phenotype for therapeutic applications, the main reasons being their well-established abilities to promote regeneration of injured tissues and to modulate immune responses. Efficacy was reported in the treatment of several animal models of inflammatory and autoimmune diseases and, in clinical settings, for the management of disorders such as GVHD, systemic lupus erythematosus, multiple sclerosis, and inflammatory bowel disease. The effects of mesenchymal stem cells are believed to be largely mediated by paracrine signals, and several secreted molecules have been identified as contributors to the net biological effect. Recently, it has been recognized that bioactive molecules can be shuttled from cell to cell packed in microvesicles, tiny portions of cytoplasm surrounded by a membrane. Coding and noncoding RNAs are also carried in such microvesicles, transferring relevant biological activity to target cells. Several reports indicate that the regenerative effect of mesenchymal stem cells can be reproduced by microvesicles isolated from their culture medium. More recent evidence suggests that the immunomodulatory effects of mesenchymal stem cells are also at least partially mediated by secreted microvesicles. These findings allow better understanding of the mechanisms involved in cell-to-cell interaction and may have interesting implications for the development of novel therapeutic tools in place of the parent cells.

  8. Morphology, proliferation, and osteogenic differentiation of mesenchymal stem cells cultured on titanium, tantalum, and chromium surfaces

    DEFF Research Database (Denmark)

    Stiehler, Maik; Lind, M.; Mygind, Tina;

    2007-01-01

    the interactions between human mesenchymal stem cells (MSCs) and smooth surfaces of titanium (Ti), tantalum (Ta), and chromium (Cr). Mean cellular area was quantified using fluorescence microscopy (4 h). Cellular proliferation was assessed by (3)H-thymidine incorporation and methylene blue cell counting assays (4...

  9. Expansion of mesenchymal stem cells using a microcarrier-based cultivation system: growth and metabolism

    NARCIS (Netherlands)

    Schop, D.; Janssen, F.W.; Borgart, E.; Bruijn, de J.D.; Dijkhuizen-Radersma, van R.

    2008-01-01

    For the continuous and fast expansion of mesenchymal stem cells (MSCs), microcarriers have gained increasing interest. The aim of this study was to evaluate the growth and metabolism profiles of MSCs, expanded in a microcarrier-based cultivation system. We investigated various cultivation conditions

  10. Tumour microenvironment and radiation response in sarcomas originating from tumourigenic human mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo Peder; Safwat, Akmal Ahmed; Burns, Jorge S.;

    2012-01-01

    Background: Resistance to radiation therapy remains a serious impediment to cancer therapy. We previously reported heterogeneity for clonogenic survival when testing in vitro radiation resistance among single cell derived clones from a human mesenchymal cancer stem cell model (hMSC). Here we aimed...

  11. 3D tissue formation : the kinetics of human mesenchymal stem cells

    NARCIS (Netherlands)

    Higuera Sierra, Gustavo Andrés

    2010-01-01

    The main thesis in this book proposes that physical phenomena underlies the formation of three-dimensional (3D) tissue. In this thesis, tissue regeneration with mesenchymal stem cells was studied through the law of conservation of mass. MSCs proliferation and 3D tissue formation were explored from 2

  12. Outcomes of Maintenance Therapy with Bortezomib after Autologous Stem Cell Transplantation for Patients with Multiple Myeloma.

    Science.gov (United States)

    Sivaraj, Dharshan; Green, Michael M; Li, Zhiguo; Sung, Anthony D; Sarantopoulos, Stefanie; Kang, Yubin; Long, Gwynn D; Horwitz, Mitchell E; Lopez, Richard D; Sullivan, Keith M; Rizzieri, David A; Chao, Nelson J; Gasparetto, Cristina

    2017-02-01

    Comprehensive recommendations for maintenance therapy after autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to the safety and efficacy of this agent compared with lenalidomide in the post-ASCT setting are limited. Therefore, we retrospectively analyzed the outcomes of 102 patients with MM who received maintenance therapy with bortezomib after ASCT at Duke University's adult bone marrow transplant clinic between 2005 and 2015. Maintenance with bortezomib was initiated between 60 and 90 days after ASCT as a single agent 1.3 mg/m(2) once every 2 weeks (n = 92) or in combination with lenalidomide (10 mg/day) (n = 10). The median age at ASCT was 64 (range, 31 to 78). Of the 99 patients with molecular data availa