Author: tcnhat

  • Comparative treatment efficiency of adipose and bone marrow derived allogenic mesenchymal stem cell transplantation in mouse models of liver fibrosis

    Abstract

    Background: The application of mesenchymal stem cell (MSC) therapy in liver fibrosis treatment has been increasingly investigated in recent years. MSCs obtained from a variety of sources (e.g. bone marrow, umbilical cord blood and adipose tissue) have been studied and have achieved remarkable results. In this study, we compared the effects of adipose-derived mesenchymal stem cells (AD-MSC) transplantation with bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation in a mouse model of liver fibrosis, induced by carbon tetrachloride (CCl4).

    Methods: Eight-week old mice were treated with CCl4 for 11 weeks to induce liver fibrosis then 5×105 cells were transplanted into mice via the tail vein.

    Results: After 21 days of transplantation, the results showed that the stem cell treated groups ameliorated better than the placebo group. MSC treated groups showed reduced AST and ALT levels, down-regulated expression of extracellular matrix (ECM) genes, and improved liver histopathology. Both sources of MSCs (bone marrow and adipose tissue) were effective in the mouse model of liver fibrosis.

    Conclusion: Our results also indicated that AD-MSC transplantation in mice accelerated liver regeneration better than BM-MSC transplantation.

    Ngày đăng: 26/06/2017
    Link: http://www.bmrat.org/index.php/BMRAT/article/view/179

  • Allogeneic Adipose-Derived Mesenchymal Stem Cell Transplantation Enhances the Expression of Angiogenic Factors in a Mouse Acute Hindlimb Ischemic Model

    Abstract

    Cell migration and molecular mechanisms during healing of damaged vascular or muscle tissues are emerging fields of interest worldwide. The study herein focuses on evaluating the role of allogenic adipose-derived mesenchymal stem cells (ADMSCs) in restoring damaged tissues. Using a hindlimb ischemic mouse model, ADMSC-mediated induction of cell migration and gene expression related to myocyte regeneration and angiogenesis were evaluated. ADMSCs were labeled with GFP (ADMSC-GFP). The proximal end of the femoral blood vessel of mice (over 6 months of age) are ligated at two positions then cut between the two ties. Hindlimb ischemic mice were randomly divided into two groups: Group I (n = 30) which was injected with PBS (100 μL) and Group II (n = 30) which was transplanted with ADMSC-GFP (106 cells/100 μL PBS) at the rectus femoris muscle. The migration of ADMSC-GFP in hindlimb was analyzed by UV-Vis system. The expression of genes related to angiogenesis and muscle tissue repair was quantified by real-time RT-PCR. The results showed that ADMSCs existed in the grafted hindlimb for 7 days. Grafted cells migrated to other damaged areas such as thigh and heel. In both groups the ischemic hindlimb showed an increased expression of several angiogenic genes, including Flt-1Flk-1, and Ang-2. In particular, the expression of Ang-2 and myogenic-related gene MyoD was significantly increased in the ADMSC-treated group compared to the PBS-treated (control) group; the expression increased at day 28 compared to day 3. The other factors, such as VE-CadherinHGFCD31Myf5, and TGF-β, were also more highly expressed in the ADMSC-treated group than in the control group. Thus, grafted ADMSCs were able to migrate to other areas in the injured hindlimb, persist for approximately 7 days, and have a significantly positive impact on stimulating expression of myogenic- and angiogenesis-related genes.

    Ngày đăng: 16/06/2017
    Link: https://link.springer.com/chapter/10.1007%2F5584_2017_63

  • ETV-2 activated proliferation of endothelial cells and attenuated acute hindlimb ischemia in mice

    Abstract

    Ischemia is the reduction of blood flow to tissues by injury of blood vessels. Depending on the sites of tissues and grade of ischemia, ischemia can cause many serious complications. This study aimed to evaluate the effects of the E-twenty six (ETS) factor Ets variant 2 (ETV2) gene expression in angiogenesis and the effect of ETV2 gene therapy in a mouse model of hindlimb ischemia. The role of ETV2 on endothelial cell proliferation was evaluated in vitro. Knockdown of ETV2 expression was done using short hairpin RNA (shRNA) lentiviral viral particles. The ETV2 viral vector was injected into the skeletal muscles at the ligated and burned sites of the hindlimb and evaluated for its efficacy as a gene therapy modality for ischemia. Vascular regeneration in mice was indirectly evaluated by changes in mouse survival, necrotic grades of the leg, normal blood oxygen saturation level (SpO2), and blood flow by trypan blue injection assay. Preliminary data showed that ETV2 expression played a role in angiogenesis of endothelial cells. ETV2 overexpression could trigger and stimulate proliferation of skeletal endothelial cells. In vivo knockdown of ETV2 expression inhibited the auto-recovery of ischemic hindlimb, while overexpression of ETV2 helped to rescue leg loss and reduce necrosis, significantly improving angiogenesis in hindlimb ischemia. Our findings demonstrate that ETV2 gene therapy is a potentially effective modality for vascular regeneration.

    Ngày đăng: 19/04/2017
    Link: https://link.springer.com/article/10.1007%2Fs11626-017-0151-4

  • Extracellular vesicles of ETV2 transfected fibroblasts stimulate endothelial cells and improve neovascularization in a murine model of hindlimb ischemia

    Abstract

    Ischemia are common conditions related to lack of blood supply to tissues. Depending on the ischemic sites, ischemia can cause different diseases, such as hindlimb ischemia, heart infarction and stroke. This study aims to evaluate how extracellular vesicles (EVs) derived from ETV2 transfected fibroblasts affect endothelial cell proliferation and neovascularization in a murine model of hindlimb ischemia. Human fibroblasts were isolated and cultured under standard conditions and expanded to the 3th passage before use in experiments. Human fibroblasts were transduced with a viral vector containing the ETV2 gene. Transduced cells were selected by puromycin treatment. These cells were further cultured for collection of EVs, which were isolated from culture supernatant. Following co-culture with endothelial cells, EVs were evaluated for their effect on endothelial cell proliferation and were directly injected into ischemic tissues of a murine model of hindlimb ischemia. The results showed that EVs could induce endothelial cell proliferation in vitro and improved neovascularization in a murine model of hindlimb ischemia. Our results suggest that EVs derived from ETV2-transfected fibroblasts can be promising non-cellular products for the regeneration of blood vessels.

    Ngày đăng: 04/04/2017
    Link: https://link.springer.com/article/10.1007%2Fs10616-017-0095-2

  • Improving stem cell engraftment to enhance functional efficacy in cardiovascular disease: where are we now?

    Abstract

    Stem cell therapy is a promising therapy for repairing damaged tissue. A growing body of research shows that stem cells work effectively in several diseases such as cardiovascular disease, hepatic disease, and diabetes. It has been shown that stem cells not only differentiate into functional cells and replace dead cells, but also release growth factors and cytokines which can recruit autologous cells. The most significant barrier to achieve clinical relevance of this treatment mode is the poor survival rate of injected cells. To improve transplantation and enhance functional outcome, investigations of gene transfection (overexpression of anti-apoptotic and antioxidant proteins), growth factor supplementation, and scaffolding matrices are being conducted. In this review, we will focus on methods to increase cell survival in stem cell transplantation as a novel treatment for cardiovascular disease.

    Ngày đăng: 31/01/2017
    Link: http://www.bmrat.org/index.php/BMRAT/article/view/146

  • Mesenchymal stem cells for diabetes mellitus treatment: new advances

    Abstract

    Mesenchymal stem cells (MSCs) are the most widely used stem cells of the human body due to ease of successful isolation and expansion for many years. In particular, from 2012 until now, MSCs have been widely clinically used to treat various diseases, including graft versus host disease (GVHD), Crohn’s disease, and knee osteoarthritis. In this review, the applications of MSCs in diabetes will be reviewed and discussed. Diabetes mellitus type 1, also known as Type 1 diabetes (T1DM), is an autoimmune disease in which immune cells attack the beta cells in islets of Langerhans (pancreatic islets). Although type 2 diabetes (T2DM) is considered to be a disease related to insulin resistance, several recent studies have shown some relation of immune dysfunction in this disease. Therefore, MSC transplantation may be a beneficial treatment for both T1DM and T2DM. MSC transplantation in preclinical trials and clinical trials for T1DM and T2DM have shown a moderate to significant improvement in diabetes without adverse side effects. In this review, we will discuss some of the updates from preclinical and clinical trials of MSC transplantation for diabetes.

    Ngày public: 31/01/2017
    Link: http://www.bmrat.org/index.php/BMRAT/article/view/144

  • Adipose tissue derived stromal vascular fraction transplantation can recover spinal cord injury in mice

    Abstract

    Introduction: Stem cell therapy is one of the most promising therapies for degenerative diseases and related injuries. Adipose tissue derived stem cells (ADSCs) exhibit some particular properties such as high production of paracrine factors. Indeed, ADSCs have been successfully used to treat diseases, including osteoarthritis, diabetic ulcer, etc.

    Methods: In this study, ADSCs were used to treat spinal cord injury (SCI) in a mouse model. Non-expanded ADSCs, from stromal vascular fractions (SVFs) isolated from both autologous and allogeneic adipose tissues, were injected into injured sites of mice at a specified dose. The SCI mouse model were generated by transection of spinal cord at vertebrae T8 – T10. After 1 week of transection, mice exhibiting completed SCI were divided into 4 groups: group 1 was control (mice without any treatment), group 2 was placebo (mice treated with platelet rich plasma (PRP)), group 3 was allogeneic SVF transplantation (mice treated with allogeneic SVFs), and group 4 was autologous SVF transplantation (mice treated with autologous SVFs). For the treatment groups, mice were transplanted with 20 µL of activated PRP or/and with 106 cells of SVF (allogeneic or autologous) into the injured position through laminectomy. The recovery of SCI was evaluated by locomotor test, sensory test and sensory-motor test at 5 weeks after transplantation. The histology of the spinal cord also was checked after 5 weeks.

    Results: The results showed that in all groups with PRP injected with or without SVFs, the inflammation was efficiently controlled. The glial scar as well as myelin defragmentation were clearly reduced. However, a significant improvement of BBB score was only recorded in mice transplanted with autologous SVFs.

    Conclusion: The results of our study show that autologous SVF transplantation in combination with PRP can be a promising therapy for SCI.

    Năm: 2016
    Link: http://www.cellstemcell.org/index.php/PSC/article/view/148

  • Autologous and allogeneic transplantation of adipose derived stem cells have similar efficacy for type 1 diabetes mellitus therapy in mouse models

    Abstract

    Introduction: Type 1 diabetes mellitus (T1D) disease is caused by lesions or dysfunction of beta cells of pancreatic islets, causing less insulin to be secreted into the blood and thereby increasing glucose levels in the blood. In this study, we evaluated and compared the efficiency of treatment for T1D using autograft and allograft adipose-derived stem cells (ADSCs). Methods: ADSCs were collected from the belly of mice before they were injected using a single dose of streptozotocin (100 mg/kg) to induce T1D. T1D mice were intravenously injected with a dose of 2×106 ADSCs into the tail vein. Therapeutic efficacy was assessed by survival rate, blood glucose levels, serum insulin levels, histology and immunohistochemistry of pancreatic islets. Results: The results showed that both autograft and allograft transplantation of ADSCs demonstrated similarities in mortality rate, blood glucose level, blood insulin level, quantity and size of pancreatic islets. Both transplantations significantly improved T1D mice, which showed a decrease in mortality rate as well as blood glucose level, and increases in blood insulin level, quantity and size of pancreatic islets. Conclusion: The similar results suggest that both autologous and allogeneic transplantations of ADSCs are promising therapy for T1D treatment.

    Năm: 2016
    Link: http://www.cellstemcell.org/index.php/PSC/article/view/142

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

    Abstract

    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 1-2×106 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.

    Năm: 2016
    Link: http://www.bmrat.org/index.php/BMRAT/article/view/141

  • Xenotransplantation of human umbilical cord derived stem cells for treatment of type 1 diabetes mellitus in mice

    Abstract

    Introduction: Type 1 diabetes mellitus disease (T1D) is an autoimmune disease in which pancreatic islets are attacked by the host’s immune system. Although this disease can be treated using some of the current methods, resistance to therapy can develop over time after a long usage of the treatments. Therefore, new strategies to treat T1D have been suggested. This study aims to treat T1D using a new approach to target this autoimmune disease; the approach involves the use of mesenchymal stem cells (MSCs) to induce immune modulation.

    Methods: Umbilical cord derived MSCs (UC-MSCs) were evaluated in this study. The cells were confirmed to be MSCs by surface profile markers and by in vitro differentiation potential into osteoblasts, adipocytes and chondroblasts. The MSCs were evaluated in a Type 1 diabetic mouse model (induced by streptozotocin (STZ)); MSCs were xenografted at a dose of 2.10cells per mouse in 100 uL of saline. T1D mice injected with saline were used as placebo. Mice were monitored for body weight, blood glucose, blood insulin, glucose tolerance test and pancreas histological analysis.

    Results: Results showed that UC-MSC xenotransplantation could improve diabetes in mice. Mouse body weight significantly increased after 6 weeks of treatment. Blood glucose levels markedly decreased while blood insulin levels strongly increased towards normal range. Recovery of the insulin positive Langerhans cells was confirmed by histological analysis.

    Conclusion: Overall, our findings suggest that UC-MSC transplantation is a promising therapy for T1D treatment.

    Năm: 2016
    Link: http://www.bmrat.org/index.php/BMRAT/article/view/140