Category: Bài báo ngoài nước

  • 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

  • Production of endothelial progenitor cells from skin fibroblasts by direct reprogramming for clinical usages

    Abstract

    Endothelial progenitor cells (EPCs) play an important role in angiogenesis. However, they exist in limited numbers in the human body. This study was aimed to produce EPCs, for autologous transplantation, using direct reprogramming of skin fibroblasts under GMP-compliant conditions. Fibroblasts were collected and cultured from the skin in DMEM/F12 medium supplemented with 5% activated platelet-rich plasma and 1% antibiotic-antimycotic solution. They were then transfected with mRNA ETV2 and incubated in culture medium under hypoxia (5% oxygen) for 14 d. Phenotype analysis of transfected cells confirmed that single-factor ETV2 transfection successfully reprogrammed dermal fibroblasts into functional EPCs. Our results showed that ETV2 mRNA combined with hypoxia can give rise to functional EPCs. The cells exhibited functional phenotypes similar to endothelial cells derived from umbilical cord vein; they expressed CD31 and VEGFR2, and formed capillary-like structures in vitro. Moreover, these EPCs could significantly improve hindlimb ischemia in mouse models. Although the direct conversion efficacy was low (3.12 ± 0.98%), altogether our study demonstrates that functional EPCs can be produced from fibroblasts and can be used in clinical applications.

    Năm: 2016
    Link: https://link.springer.com/article/10.1007%2Fs11626-016-0106-1

  • The effects of transplanted cells in stem cell therapy for myocardial ischemia

    Abstract

    It is known that myocardial infarction (MI) causes damages to the heart tissue and that present medical therapies, such as medication, stenting and coronary artery bypass surgery, cannot recover the injured heart. Fortunately, advances in stem cell research have brought hope of full heart recovery for myocardial ischemia patients. There have been many studies using cell therapies for myocardial ischemia, from preclinical trials to clinical trials. However, the biggest concern is the effect of transplanted cells in myocardial recovery. This review will focus on analyzing both the positive and negative effects of transplanted cells in myocardial recovery to better understand the underlying biological mechanisms and ways to evaluate safety and efficacy of cell transplantation in myocardial ischemia treatment.

    Năm: 2016
    Link: http://www.bmrat.org/index.php/BMRAT/article/view/136

  • Umbilical cord derived stem cell (ModulatistTM) transplantation for severe chronic obstructive pulmonary disease: a report of two cases

    Abstract

    Introduction: Chronic obstructive pulmonary disease (COPD) is a chronic disease affecting the airway of the respiratory system. COPD cases have rapidly increased in recent years, with the disease becoming the fourth leading cause of death worldwide. Stem cell transplantation is a new approach to treat COPD. In this study we report in two cases the use of transplanted stem cells to treat COPD.

    Methods: Umbilical cord derived stem cells (ModulatistTM) were used in the study. ModulatistTM was prepared according to previous published studies. Two patients with late stage COPD (stage IV) were transfused with Modulatist at a dose of 106 cells/kg. Patients were evaluated by the COPD assessment test (CAT) score as well as the Modified Medical Research Council Dyspnea Scale (mMRC) score, before and after transplantation (1, 3 and 5 months post transplantation).

    Results: Results showed that ModulatistTM transplantation significantly improved sever COPD, especially after 3 months. At that time point, the two patients receiving ModulatistTM showed a significantly improvement, from late-stage of COPD (stage IV) to stage I.

    Conclusion: Although these initial results suggest that ModulatistTMtransplantation is a promising therapy, more clinical studies in COPD patients are warranted to evaluate efficacy.

    Năm: 2016
    Link: http://www.bmrat.org/index.php/bmrat/article/view/130

  • Stem cell drugs: the next generation of pharmaceutical products

    Abstract

    Stem cells represent a new treatment option in medicine and pharmacy. Stem cells have been increasingly used for the treatment of many diseases. In fact, they have spurred a new age of medicine called regenerative medicine. In recent years, regenerative medicine has become a new revolution in disease treatment, especially with the use of stem cell drugs. Stem cell drugs refer to live stem cell based products that used as drugs for particular diseases. Unlike autologous stem cell transplantation, stem cell drugs are “off-the-shelf” products that are ready to be used without requirement of any further manipulation. This review aims to summarize some of the approved stem cell drugs, and discuss the revolution of regenerative medicine and personalized medicine. As well, the review will discuss how stem cell drugs have led to a new direction in stem cell therapy, providing a new platform for patient needs.

    Năm 2016
    Link: http://www.bmrat.org/index.php/bmrat/article/view/128

  • Adipose derived stem cell transplantation is better than bone marrow mesenchymal stem cell transplantation in treating hindlimb ischemia in mice

    Abstract

    Introduction: Bone marrow derived MSCs (BM-MSCs) and adipose derived MSCs (AD-MSCs) are among the types of stem cells most commonly studied. Our study aims to compare the therapeutic efficacy of allograft AD-MSCs versus BM-MSCs in a mouse model of hindlimb ischemia. Methods: AD-MSCs were isolated from belly fat and BM-MSCs were isolated from femur bone marrow. They were used to treat mice with acute hindlimb ischemia. Treatment efficacy was compared among 4 groups: injected with BM-MSCs, injected with AD-MSCs, non-treated and injected with phosphate buffered saline. Mice in the groups were evaluated for the following: necrosis grade of leg, leg edema, blood flow, muscle cell restructure and new blood vessel formation. Results: Results showed that AD-MSC transplantation significantly recovered acute limb ischemia, with 76.5% of mice fully recovered, while the ratio was only 48.5% in BM-MSC transplanted group, and 0% in the non-treated and PBS groups. Evaluation of leg edema, blood flow, muscle cell restructure and new blood vessel formation also supported the observation that AD-MSC transplantation was superior over BM-MSC transplantation. Conclusion: Therefore, AD-MSCs may serve as the more suitable MSC for hindlimb ischemia treatment and angiogenesis therapy.

    Năm 2016
    Link: http://www.bmrat.org/bmrat/article/view/8

  • Overexpress of CD47 does not alter the stemness of MCF-7 breast cancer cells

    Abstract

    Background: CD47 is a transmembrane glycoprotein expressed on all cells in the body and particularly overexpressed on cancer cells and cancer stem cells of both hematologic and solid malignancies. In the immune system, CD47 acts as a “don’t eat me” signal, inhibiting phagocytosis by macrophages by interaction with signal regulatory protein α (SIRPα). In cancer, CD47 promotes tumor invasion and metastasis. This study aimed to evaluate the stemness of breast cancer cells when CD47 is overexpressed.

    Methods: MCF-7 breast cancer cells were transfected with plasmid pcDNA3.4-CD47 containing the CD47 gene. The stemness of the transduced MCF7 cell population was evaluated by expression of CD44 and CD24 markers, anti-tumor drug resistance and mammosphere formation.

    Results: Transfection of plasmid pcDNA3.4-CD47 significantly increased the expression of CD47 in MCF-7 cells. The overexpression of CD47 in transfected MCF-7 cells led to a significant increase in the CD44+CD24– population, but did not increase doxorubicin resistance of the cells or their capacity to form mammospheres.

    Conclusion: CD47 overexpression enhances the CD44+CD24phenotype of breast cancer cells as observed by an increase in the CD44+CD24– expressing population. However, these changes are insufficient to increase the stemness of breast cancer cells.

    Năm: 2016
  • Hepatocyte growth factor improves direct reprogramming of fibroblasts towards endothelial progenitor cells via ETV2 transduction

    Abstract

    Human fibroblasts can be differentiated into endothelial progenitor cells by direct reprogramming via ETV-2 transfection. Previously, we have shown that the efficacy of direct reprogramming can be enhanced by hypoxia treatment. In this study, we aim to investigate whether the efficacy of direct reprogramming of fibroblasts into EPCs via Ets variant gene 2 (ETV2) transfection can be increased with hepatocyte growth factor (HGF) treatment. Foreskin-derived fibroblasts were cultured in standard medium (DMEM/F12 supplemented with fetal bovine serum). They were then transduced with a viral vector expressing ETV2 in culture medium supplemented with HGF. The transduced fibroblasts were cultured in endothelial cell medium supplemented with HGF for 28 days. The efficacy of direct reprogramming was evaluated based on expression of CD31 and VEGFR2 markers by transduced cells. Phenotypic and functional characterization of induced EPCs were also confirmed by expression of particular genes and in vitro angiogenesis assays. Our results showed that HGF significantly increased the efficacy of direct reprogramming of fibroblasts towards EPCs via ETV2 transcription factors; efficiency increased from 5.41±1.51% for ETV2 transduction alone to 12.31±2.15% for ETV2 transduction combined with HGF treatment. These findings suggest the rationale for combined use of ETV2 and HGF in direct in vitro reprogramming of fibroblasts into EPCs.

    Năm: 2016
    Link: http://www.bmrat.org/index.php/BMRAT/article/view/7″

  • In vitro expansion of mesenchymal stem cells for clinical use

    In vitro expansion of mesenchymal stem cells for clinical use

    Phuc Van Pham, Ngoc Bich Vu

     

    Abstract

    Mesenchymal stem cells (MSCs) now are popular stem cells for clinical applications. To date, MSCs were accepted in various disease treatments with several FDA approved treatments in some countries. One important requirement for the clinical usage of stem cells is the production of stem cells. Actually, the treatment efficacy of MSC transplantation depends on the quality of transplanted MSCs. This review aimed to present some guidelines for MSC production according to good manufacturing practice that helps to maintain the quality of stem cells from batch to batch as well as the clinical satisfaction.

    Keywords

     

    Good manufacturing practice, Mesenchymal stem cells, Clinical application, Stem cell therapy.