Mesenchymal stem cells (MSCs) have recently generated great interest in the fields of regenerative medicine and immunotherapy due to their unique biologic properties. In this review we attempt to provide an overview of the current clinical status of MSC therapy, primarily focusing on immunomodulatory and regenerative or tissue repair applications of MSCs. In addition, current manufacturing is reviewed with attention to variation in practices (e.g., starting material, approach to culture and product testing). There is considerable variation among the 218 clinical trials assessed here; variations include proposed mechanisms of action, optimal dosing strategy, and route of administration. To ensure the greatest likelihood of success in clinical trials as the field progresses, attention must be given to the optimization of MSC culture.

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Progressive and inexorable beta-cell dysfunction is the hallmark of type 2 diabetes mellitus (T2DM) and beta-cell regeneration using stem cell therapy may prove to be an effective modality. A total of 10 patients (8 men) with T2DM for >5 years, failure of triple oral antidiabetic drugs, currently on insulin (> or = 0.7 U/kg/day) at least for 1 year, and glutamic acid decarboxylase antibody negative were included. Patients on stable doses of medications for past 3 months were recruited. Primary end points were reduction in insulin requirement by > or = 50% and improvement in glucagon-stimulated C-peptide levels at the end of 6 months of autologous bone marrow-derived stem cell transplantation (SCT), while secondary end points were a change in weight and HbA1c and lipid levels as compared to baseline. Seven patients were responders and showed a reduction in insulin requirement by 75% as compared to baseline. Mean duration to achieve the primary objective was 48 days. Three patients were able to discontinue insulin completely, although it was short-lived in one. Mean HbA1c reduction was 1% and 3 of the 7 responders had HbA1c value <7%. A significant weight loss of 5.5 kg was noted in the responders, whereas, nonresponders gained 2.2 kg of weight. However, weight loss did not correlate with reduction in insulin requirement (r = 0.68, P = 0.06). There was a significant improvement in both fasting and glucagon-stimulated C-peptide level in the group (P = 0.03) and responders (P = 0.03). HOMA-B increased significantly in the whole group (P = 0.02) and responders (P = 0.04) whereas, HOMA-IR did not change significantly (P = 0.74). Reduction in insulin doses correlated with stimulated C-peptide response at the baseline (r = 0.83, P = 0.047) and mononuclear cell count of infused stem cells (r = 0.57, P = 0.04). No serious adverse effects were noted. Our observations indicate that SCT is a safe and effective modality of treatment to improve beta-cell function in patients with T2DM. However, further large-scale studies are needed to substantiate these observations.

Drugs targeting β-cells have provided new options in the management of T2DM; however, their role in β-cell regeneration remains elusive. The recent emergence of cell-based therapies such as autologous bone marrow-derived mesenchymal stem cells (ABM-MSCs) and mononuclear cells (ABM-MNCs) seems to offer a pragmatic approach to augment β-cell function/mass. This study aims to examine the efficacy and safety of ABM-MSC and ABM-MNC transplantation in T2DM and explores alterations in glucose-insulin homeostasis by metabolic studies. Thirty patients of T2DM with duration of disease ≥5 years, receiving triple oral antidiabetic drugs along with insulin (≥0.4 IU/Kg/day) with HbA1c ≤7.5%(≤58.0 mmol/mol), were randomized to receive ABM-MSCs or ABM-MNCs through targeted approach and a sham procedure (n = 10 each). The primary endpoint was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c <7.0% (<53.0 mmol/mol) during 1-year follow-up. Six of 10 (60%) patients in both the ABM-MSC and ABM-MNC groups, but none in the control group, achieved the primary endpoint. At 12 months, there was a significant reduction in insulin requirement in ABM-MSC (P < 0.05) and ABM-MNC groups (P < 0.05), but not in controls (P = 0.447). There was a significant increase in second-phase C-peptide response during hyperglycemic clamp in the ABM-MNC (P < 0.05) group, whereas a significant improvement in insulin sensitivity index (P < 0.05) accompanied with an increase in insulin receptor substrate-1 gene expression was observed in the ABM-MSC group. In conclusion, both ABM-MSCs and ABM-MNCs result in sustained reduction in insulin doses in T2DM. Improvement in insulin sensitivity with MSCs and increase in C-peptide response with MNCs provide newer insights in cell-based therapies.

Intra-arterial infusion of stem cells can be carried out safely in the subacute stage of ischemic stroke. Improved clinical outcomes were observed with intra-arterial stem cell therapy; however, studies with larger cohorts are needed to validate the results.

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Background:The development of anti-red blood cell antibodies (both allo-and autoantibodies) remains a major problem in thalassemia major patients. We studied the frequency of red blood cell (RBC) alloimmunization and autoimmunization among thalassemia patients who received regular transfusions at our center and analyzed the factors, which may be responsible for development of these antibodies.Materials and Methods:The study was carried out on 319 multiply transfused patients with β-thalassemia major registered with thalassemia clinic at our institute. Clinical and transfusion records of all the patients were examined for age of patients, age at initiation of transfusion therapy, total number of blood units transfused, transfusion interval, status of splenectomy or other interventions. Alloantibody screening and identification was done using three cell and 11 cell panel (Diapanel, Bio-rad, Switzerland) respectively. To detect autoantibodies, autocontrol was carried out using polyspecific coombs (IgG + C3d) gel cards.Results:Eighteen patients out of total 319 patients (5.64%) developed alloantibodies and 90 (28.2%) developed autoantibodies. Nine out of 18 patients with alloantibodies also had autoantibodies. Age at first transfusion was significantly higher in alloimmunized than non-immunized patients (P = 0.042). Out of 23 alloantibodies, 52.17% belonged to Rh blood group system (Anti-E = 17%, Anti D = 13%, Anti-C = 13%, Anti-Cw = 9%), 35% belonged to Kell blood group system, 9% of Kidd and 4% of Xg blood group system.Conclusion:Alloimmunization was detected in 5.64% of multitransfused thalassemia patients. Rh and Kell blood group system antibodies accounted for more than 80% of alloantibodies. This study re-emphasizes the need for RBC antigen typing before first transfusion and issue of antigen matched blood (at least for Rh and Kell antigen). Early institution of transfusion therapy after diagnosis is another means of decreasing alloimmunization.

The majority of alloantibodies detected in the current study were clinically significant. Thus, pre-transfusion antibody screening on patients' samples prior to crossmatching needs to be initiated in India to ensure safe transfusion practice.