Bone Marrow-Derived Stem Cell Transplantation for the Treatment of Insulin-Dependent Diabetes

Abstract

■ AbstractThe bone marrow is an invaluable source of adult pluripotent stem cells, as it gives rise to hematopoietic stem cells, endothelial progenitor cells, and mesenchymal cells, amongst others. The use of bone marrow-derived stem cell (BMSC) transplantation (BMT) may assist in achieving tissue repair and regeneration, and in modulating immune responses in the context of autoimmunity and transplantation. Ongoing clinical trials are evaluating the effects of BMSC to preserve functional beta-cell mass in subjects with type 1 and type 2 diabetes, and to favor engraftment and survival of transplanted islets. Additional trials are evaluating the impact of BMT (i.e., mesenchymal stem cells) on the progression of diabetes complications. This article reviews the progress in the field of BMSC for the treatment of subjects with insulindependent diabetes, by combining allogeneic islet transplantation with donor-specific BMSC. Clinical data is summarized from pilot studies performed at our research center over the last two decades.

C-peptide increase in chronic type 1 diabetic patients treated with autologous bone marrow cell transplantation through pancreatic artery catheterization: Three years follow-up

“…The results are clinically significant and persistent for three years. A recent clinical trial has concluded that bone marrow stem cells transplantation with immunosuppression showed safety, tolerability and effectiveness in most of 200 subjects recently diagnosed with type 1 diabetes, but immunosuppression caused major complications [38]. Comparing this study with our experience, no significant differences have been observed in the rates of disease progression, as measured by the stimulated Cpeptide levels at one year follow-up point.…”

“…In type 1 diabetes recently diagnosis reported significant increases in C-peptide after transplantation of allogeneic adult stem cells with immune suppression [36][37][38].…”

Immuno-metabolism and adipose tissue: The key role of hematopoietic stem cells

“…It was based on immune ablation aimed to destroy self-reacting immune cells, and regeneration of a new functional immune system in which immune tolerance could normally effect [65]. Similar strategies have been used in patients with type 2 diabetes with positive results [66]. In animals, data were mostly obtained from chimeric mice models: in streptozotocininduced diabetic mouse, an improvement of metabolic parameters is achieved after transplantation of non-diabetic BM cells, although hematopoietic parameters were not analyzed [67e70].…”

B6.g7 mice reconstituted with BDC2·5 non-obese diabetic (BDC2·5NOD) stem cells do not develop autoimmune diabetes

“…Further investigation is required to determine the mechanistic basis of the different proportions of host-derived CD4 + T cells in these organs. Fatal infections due to the prolonged immunosuppression or insufficient recovery of T cells following autologous HCT or allogenic HCT limit the use of these methods for treating T1D [41]. Use of in-vitro expanded CD4 + Tregs has been proposed as a means to induce tolerance and control autoimmunity [42].…”