Foxp3 gene expression in multiple sclerosis patients pre- and post mesenchymal stem cell therapy

Multiple Sclerosis [MS] is an inflammatory demyelinating and neurodegenerative disorder of the central nervous system [CNS], which mainly affects young adults. Activated T lymphocytes promote the neuro-inflammatory cascade of MS by secreting pro-inflammatory cytokines and play a significant role in its pathogenesis. T lymphocytes may trigger the inflammation, which in turn leads to axonal loss and neurodegeneration observed in the course of MS. Currently, there is no cure for MS, however, one of the most promising neuroprotective research tools consists of the use of bone marrow derived mesenchymal stem cells [MSC]. This method promotes immune system regulation and possibly induces neurological repair and re-myelination of the damaged axons. Recent studies have shown that MSC exert an immune regulatory function and induce T regulatory-cell proliferation, therefore, it may serve as a potentially useful treatment for immune-mediated diseases such as MS. In this pilot study a group of MS patients underwent MSC therapy and we assayed the expression of an X-linked transcription factor, FoxP3, as a specific marker of T Regulatory cells in peripheral blood, prior to and after the treatment. Using q RT-PCR for measurement of expression of FoxP3 by peripheral blood mononuclear cells, we found that in all subjects, except for one, the expression of FoxP3 at 6 months after intrathecal injection of MSC was significantly higher than the levels prior to treatment. Such significant enhanced expression of FoxP3 associated with clinical stability. Findings from this pilot study further support the potential of bone marrow derived MSC for treatment of MS patients

Autologous in vitro expanded mesenchymal stem cell therapy for human old myocardial infarction

Stem cell transplantation after myocardial infarction has been claimed to restore cardiac function. Mesenchymal stem cells attract a lot of attention because of the feasibility of in vivo and ex vivo differentiation to cardiomyocytes and endothelial cells as well as their trophic effect on tissue repair. In this study, we investigated the efficacy of autologous bone marrow derived mesenchymal stem cells in improving heart function in patients with old myocardial infarction. Eight patients with old myocardial infarction and proper inclusion criteria were injected with mesenchymal stem cells at the time of coronary artery bypass grafting or percutaneous coronary intervention [test group] and compared with eight matched patients who received the same treatment without mesenchymal stem cell injection [control group]. Evaluation of heart function was done by echocardiography plus single-photon emission computed tomography before and six months after the procedure. Serial clinical examination was performed every month through New York Heart Association class. The mean New York Heart Association class and single-photon emission computed tomography scan results decreased significantly in the test group [P=0.000 and 0.002, respectively] and in the control group [P=0.049 and 0.007, respectively] after the procedure at six months follow-up. Left ventricular ejection fraction increased significantly in the test group [P< 0.005] but not in the control group. In comparison between the test and control groups the results of New York Heart Association class assessment and single-photon emission computed tomography demonstrated significant improvement in the test group [P=0.005 and 0.013, respectively]. There were no significant differences between the baseline variables in the two groups. In conclusion transplantation of ex vivo expanded bone marrow derived mesenchymal stem cell in patients with old myocardial infarction is a safe and feasible procedure. These cells improve the cardiac fimction without serious adverse effects

Does mesenchymal stem cell therapy help multiple sclerosis patients? report of a pilot study

Mesenchymal stem cells [MSCs] with their potential to differentiate into mesodermal and non-mesodermal lineages have several immunomodulatory characteristics. These properties make them promising tools in cell and gene therapy. To evaluate the potential therapeutic applications of autologous MSC in improving clinical manifestations of MS patients. Ten patients were included in this pilot study. All had progressive disease that had not responded to disease modifying agents including Mitoxantrone. Their Expanded Disability Status Scale [EDSS] score ranged from 3.5 to 6. Patients were injected intrathecally with culture expanded MSCs. They were followed with monthly neurological assessment and a MRI scan at the end of the first year. During 13 to 26 months of follow up [mean: 19 months], the EDSS of one patient improved from 5 to 2.5 score. Four patients showed no change in EDSS. Five patients' EDSS increased from 0.5 to 2.5. In the functional system assessment, six patients showed some degree of improvement in their sensory, pyramidal, and cerebellar functions. One showed no difference in clinical assessment and three deteriorated. The result of MRI assessment after 12 months was as following: seven patients with no difference, two showed an extra plaque, and one patient showed decrease in the number of plaques. This preliminary report emphasizes on the feasibility of autologous MSC for treatment of MS patients. However, in order to draw a definitive conclusion a larger sample size is required

Repair of old myocardial infarction by intracoronary transplantation of autologous bone marrow mesenchymal stem cells: a pilot clinical trial

Experimental and clinical studies have shown that intracoronary transplantation of autologous bone marrow mesenchymal stem cells [BMSCs] has resulted in regenerated infarcted myocardium and improved left ventricular [LV] function. The aim of this pilot study was to assess the benefical effects of intracoronary transplantation of BMSC in patients with old myocardial infarction [OMI]. Autologous BMSCs were transplanted by the intracoronary method via percutaneous transluminal coronary balloon angioplasty [PTCA] in five patients with old myocardial infarction. Time from myocardial infarction [MI] to cell therapy was 5.2 +/- 3.11 months [mean +/- SD]. All patients were <70 years old [32-61 years] and had significant LV dysfunction [LV ejection fraction, mean +/- SD, 34% +/- 10.83%], and severe wall motion abnormality [akinesia and / dyskinesia] at the location of infarcted area. Follow up angiography was performed 6-9 months [mean +/- SD,7 +/- 1.4 months] after BMSC transplantation, which revealed an increased trend in the LV ejection fraction [LVEF] of patients after treatment [LVEF: Mean +/- SD from 34% +/- 10.83% to 46.25% +/- 9.46%, P= 0.051 and median from 35% to 42.5%]. Clinical follow up [for 12-18 months] also revealed appreciable improvement in their symptoms or functional class [dyspnea from New York Heart Association[NYHA]-Class Sha-IV to I-II and Chest discomfort from Canadian Cardiovascular Society [CCS] Class II-IV to I-II]. Intracoronary transplantation of autologous BMSC in patients with old myocardial infarction appears to be feasible, safe and effective .The therapeutic effect could be attributed to BMSCs ability to regenerate myocardium

Ethics of tissue and stem cell trasplantation

Tissue and cell transplantation are regarded as a popular procedure in clinical sciences, prospecting a new horizon for several incurable diseases. Along with its usefulness, many ethical concerns accompany this development. The ethical issue of organ transplant is unique to the source used which includes: living related, living unrelated, cadaveric, and xenotransplant. Obtaining organs has a separate set of ethical concerns which are discussed under two headings, namely salvage and donation. Then there is the issue of organ marketing and the ethical, social, and economical issues it encompasses. All these are active areas of debate, and we have touched upon them by turn. This century has brought a new aspect of transplantation into the light, stem cell transplantation. Here we present some work done recently on mesenchymal stem cells and their outcome. These cells are now being employed in the therapy of some incurable ailments. It seems this kind of transplantation, although possessing its own range of issues, could prove to be the way of the future