Iranian Journal of Public Health
Volume:44 Issue: 2, Feb 2015

Stem cell therapy is a new treatment option for different diseases. The aim of this systematic review is assessing the articles that focus on SCT in Iran and evaluate the amount of their success, failure and complication. Systematic search was conducted for finding English and Persian papers (controlled trials and cohort studies with follow up) published before March 2015. We searched PubMed, ISI, and SCOPUS as the main international electronic data sources, as well as Iranmedex, Irandoc, andSID as the main domestic databases. Quality assessment of clinical trial and cohort study was performed based on the Consolidated Standards of Reporting Trials (CONSORT) and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) check lists respectively. The 19 published articles in this systematic review included 2 cohort, 13 clinical trial, 3 open label clinical trial and 1 clinical trial pilot study. The stem cell types for transplantation were Mesenchymal (63.15%), mononuclear (31.6%), and fetal liver cell suspension (5.6%). The most SCT was performed at Tehran (68.42%), Shiraz (15.8%), Kerman & Isfahan hospitals (5.26%). The main diseases were decompensated cirrhosis and myocardial infarction (26.31%), MS (15.78%), DM (10.52%), Burger disease, neuroblastoma, sub-acute spinal cord injury and osteoarthritis (5.26%). The most of cells transplantation are performed successfully in Iran. Cell transplantation may be safely administered to treat patients with disabling disease.

The purpose of the current study was to present an overview of different types of stem-cells and their application for treatment different degenerative disorders with specific focus on ongoing clinical trials. For the purpose of the current narrative review article, a comprehensive search was carried out on the existing literature in Google Scholar, PubMed and Scopus using the keywords: stem-cell (fetal and mesenchymal), regenerative. Relevant articles published from 1957 to 2013 are extracted and presented. During the past decades, different types of stem-cells (including adult and fetal) have been used for treatment of a wide range of immunologic (Severe Combined Immunodeficiency, Di George syndrome), neurologic (Parkinson’s disease, Huntington Chorea, Cerebral Palsy), musculoskeletal (ALS), and cardiovascular diseases (heart failure and cardiomyopathies) as well as chronic and acute ulcers, and diabetes. The results of our study demonstrated that during the past decades, stem-cell technology has been applied for treatment of a wide range of degenerative disorders with considerable success. The current ongoing clinical trials clearly demonstrate a great potential and a promising future for the technology in terms of offering curative treatment for a wide range of hitherto-incurable diseases.

Cell-based treatments are currently being actively received great attention among scientists and clinicians for a variety of diseases as well as diabetes. The aim of this study was to investigate the effect of allotransplantation of fetal liver-derived cell suspension in patients with type 1 diabetes. Patients with type 1 diabetes (n=16) aged 6-30 years-old were included in the study. Fetal liver-derived cell suspension was transplanted by the means of intravenous injection patient. In most of patient, blood glucose levels gradually decreased within the first day of infusion. Insulin independence occurred in 3 patients out of the 16 (18.7%) for 4 to 24 months. They showed increasing levels of serum c-peptide along with decreasing of levels of HbA1c level. In other patients, no significant changes in parameters of diabetes control were observed. Findings of this study indicated that transplantation of fetal stem cells could, although not permanently, be an effective therapeutic intervention in patients with type 1 diabetes. To demonstrate effectiveness of stem-cell therapy for treatment of diabetes, more clinical trials with stricter inclusion criteria, modified protocols, and larger number of patients and are necessary as well as long periods of follow up.

Stem-cell technology has been advocated as a potentially curative option for treatment of both type 1 and type 2 diabetes. In the current study, we aimed to assess the effectiveness of allotransplantation of fetal liver-derived cells for treatment of patients with type 1 diabetes. For the purpose of the current study, 72 patients with recently diagnosed type 1 DM were recruited and fetal liver-derived cell suspension was administered by the means of intravenous injection. Anthropometric measurements and clinical data such as body mass index, duration of the disease, daily insulin requirement were recorded as well as some of laboratory indicators of favorable therapeutic response (hemoglobin A1c, c-peptide) before and after the intention at 0, 1, 3, 6 and 12 months following the intervention. Administration of fetal liver-derived fetal stem-cells resulted in significant changes in indicators of diabetes control in the patients. Required daily insulin dose and HbA1c showed significant changes, and c-peptide levels decreased significantly during the first three months of follow up period (P= 0.000) although they started the decrease after that point. Stem-cell therapy resulted in significant changes in indicators of diabetes control and beta-cell function. More studies are required to demonstrate effectiveness of stem-cell therapy for type 1 diabetes.

Stem-cell therapy plays a preventive role for different complications of diabetes, including diabetes nephropathy. The current phase 3 single-arm clinical trial is designed to investigate the potential protective effect of allotransplantation of fetal liver-derived cell suspension in diabetic nephropathy. Seventy-four diabetic patients with type 1 were selected according to the inclusion criteria defined and underwent the procedure of transplantation fetal liver-derived stem-cells. Patients were followed for a period on 24 months and indicators of diabetes and diabetes nephropathy (HbA1C, ACR, Cr and GFR) were monitored during the whole time. Statistical analysis was conducted with SPSS Vers.16 and one-way repeated measure ANOVA was used. The GFR values significantly increased during the 24 months period of follow up. Stem-cell therapy can play a significant protective role in prevention from diabetic nephropathy.

Although the pathogenesis of diabetes type 1 (T1D) is not fully elucidated. Different clusters of lymphocytes such as CD4+ and CD8+ T cells are involved in it. Moreover, the mechanism of how stem-cell therapy results in significant therapeutic outcomes in diabetes remains obscure. In the current study, we aimed to analyze lymphocyte subsets in patients with T1D before and after treatment with Liver-derived Fetal Stem-cells, and investigated the potential underlying immunological mechanism of therapeutic effects of stem-cell therapy. Seventy-two patients with T1D were selected for our study and underwent allotransplantation of liver-derived fetal stem-cells. Relative counts of peripheral blood T and B lymphocyte subsets were detected by the means of flow cytometry analysis. Our results demonstrated that administration of fetal liver-derived fetal stem-cells resulted in significant changes in the subpopulations of lymphocytes of the patients, more specifically, levels of CD4+, CD8+, CD16+, and CD19+ lymphocytes. The findings of this study demonstrated that different subsets of lymphocytes significantly change following stem-cell therapy for diabetes. As it is demonstrated that immunological mechanisms are involved in pathogenesis of diabetes, these changes can suggest that therapeutic effect of stem-cell therapy for diabetes may be exerted via alternations in different lymphocyte subsets.

The aim of the present clinical trial was to investigate the efficacy of autologous bone marrow mesenchymal stem cells (BM-MSCs) in glycemic control of diabetic patients without using any immunosuppressive drugs over a nine-month period. Twenty-three patients with T1DM, at 5 to 30 years of age and in both sexes, participated in this study. This trial consisted of two phases; in the end of the first phase (three month after the transplantation), if the patient still needed exogenous insulin to control his/her glycemic state, the second phase of study was performed. In both phases, 100 milliliter of mixed mesenchymal stem cells and normal saline containing 2×10⁶ autologous cells/kg for each patient was delivered to patients through cubital vein. All patients were evaluated at 1, 3, 6 and 9 months after the procedure. Twenty-one patients underwent a second injection. Nine patients (39%) responded positively and 14 patients (61%) responded negatively based on their HbA1c levels and insulin requirements in both injections. Two patients became insulin-free during two rounds of injections. In responder patients, mean levels of C-peptide and HbA1c as well as prescribed insulin dosage significantly decreased compared to baseline measures (P=0.002, P=0.007 and P<0.001). In the second phase, responder patients did not show significant reduction in C-peptide levels compared to the baseline of the second phase. Mean levels of HbA1c and prescribed insulin dosage significantly decreased in comparison to the beginning of the study (P<0.05). Transplantation of BM-MSC can be viewed as a promising, simple, safe, and efficient therapeutic modality for T1DM.

Cell therapy has emerged as a promising curative intervention for several diseases including diabetes and Wolfram Syndrome (WS). The current study aimed to assess the effectiveness of clinical application of fetal-liver derived stem cells for treatment of patients with WS. Six patients with WS aged 23-34 (mean: 29.50, SD: 4.76) were recruited for the current phase 3 single-arm clinical trial. The participants underwent fetal liver-derived hematopoietic stem cell transplantation. In order to evaluate the effectiveness of transplantation, glycemic control indexes were measured at regular follow-up sessions. One patient (out of six) experienced a 6 months insulin-free period with acceptable HbA1c levels. In another patient with history of recurrent hypoglycemic attacks, the frequency of bout of attacks remarkably decreased. There was no significant change in other patients. Stem-cell therapy may represent a new method for treatment of patients with Wolfram Syndrome.

The clinical potentials of stem cells in cell-based therapies have raised great hopes in diabetes mellitus as well. However, there are complex ethical, legal, and socio-cultural issues surrounding the subject. In this paper, we intend to review in brief the main ethical issues for endocrinologists and other clinicians who are interested and work in the field of cell therapy and research.

To date, stem cell therapy is a novel treatment method especially in irreversible end organ damage. We present a case of a 21-yr-old man, who admitted in Sina Hospital, Tehran University of Medical Sciences, Iran with open left femur fracture following car accident. Developing fat emboli syndrome led to cardiac arrest. Despite of efforts to optimize supportive care and neuroprotective strategies, the level and content of conscious did not improve. We performed stem cell therapy and he was discharged home with mild neurologic deficit on hospital day 116. This is the first case of stem cell therapy applied to a postarrest victim with severe evidently irreversible neurological injuries. This therapy could be considered to improve neurological recovery in patients following cardiac arrest.