Cotransplantation of adipose tissue-derived insulin-secreting mesenchymal stem cells and hematopoietic stem cells: A novel therapy for insulin-dependent diabetes mellitus

Abstract

Aims. Insulin dependent diabetes mellitus (IDDM) is believed to be an autoimmune disorder with disturbed glucose/insulin metabolism, requiring life-long insulin replacement therapy (IRT), 30 of patients develop end-organ failure. We present our experience of cotransplantation of adipose tissue derived insulin-secreting mesenchymal stem cells (IS-AD-MSC) and cultured bone marrow (CBM) as IRT for these patients. Methods. This was a prospective open-labeled clinical trial to test efficacy and safety of IS-AD-MSC+CBM co-transplantation to treat IDDM, approved by the institutional review board after informed consent in 11 (males: females: 7: 4) patients with 1-24-year disease duration, in age group: 13-43 years, on mean values of exogenous insulin requirement of 1.14 units/kgBW/day, glycosylated hemoglobin (Hb1Ac): 8.47%, and c-peptide levels: 0.1ng/mL. Intraportal infusion of xenogeneic-free IS-AD-MSC from living donors, subjected to defined culture conditions and phenotypically differentiated to insulin-secreting cells, with mean quantum: 1.5mL, expressing Pax-6, Isl-1, and pdx-1, cell counts: 2.1 × 103/μL, CD45-/90+/73+:40/30.1%, C-Peptide level:1.8ng/mL, and insulin level: 339.3 IU/mL with CBM mean quantum: 96.3mL and cell counts: 28.1 × 103/μL, CD45-/34 +:0.62, was carried out. Results. All were successfully transplanted without any untoward effect. Over mean followup of 23 months, they had a decreased mean exogenous insulin requirement to 0.63units/kgBW/day, Hb1Ac to 7.39, raised serum c-peptide levels to 0.38ng/mL, and became free of diabetic ketoacidosis events with mean 2.5Kg weight gain on normal vegetarian diet and physical activities. Conclusion. This is the first report of treating IDDM with insulin-secreting-AD-MSC+CBM safely and effectively with relatively simple techniques. Copyright © 2010 A. V. Vanikar et al.