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/kg BW/day, glycosylated hemoglobin (Hb1Ac): 8.47%, and c-peptide levels: 0.1 ng/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: 1.5 mL, expressing Pax-6, Isl-1, and pdx-1, cell counts: 2.1 × 103/μL, CD45−/90+/73+:40/30.1%, C-Peptide level:1.8 ng/mL, and insulin level: 339.3 IU/mL with CBM mean quantum: 96.3 mL 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 0.63 units/kgBW/day, Hb1Ac to 7.39%, raised serum c-peptide levels to 0.38 ng/mL, and became free of diabetic ketoacidosis events with mean 2.5 Kg 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.

Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatory cytokines and the p38 MAPK signaling pathway

“…However, the use of BMMSCs is still problematic because of the low number of MSCs found in bone marrow aspirates and the invasive procedure associated with obtaining them. When (17) reported that co-transplantation of adipose tissuederived insulin-secreting MSCs and hematopoietic stem cells is beneficial in reducing exogenous insulin requirement in patients with insulin-dependent diabetes mellitus. It has also been demonstrated that transplantation of ADMSCs attenuates diabetic bladder dysfunction and diabetic retinopathy in a diabetic rat model (18,19).…”

Autologous Adipose Tissue Derived Insulin-Secreting Mesenchymal Stem Cell Transplantation In Late Onset of Autoimmune Mediated Diabetes Mellitus (LADA) – Case Report

“…In vitro functionality of these cells was also confirmed by insulin production and release in a glucose-responsive manner. [4][5][6] We decided to infuse the cells in portal circulation since liver is the most tolerogenic organ 7 . LADA is believed to be an auto-immune disorder and once the cells are infused in to thymus, it helps in preventing the rejection of these cells by inducing central tolerance 8 .…”

Applicability of Adipose-Derived Stem Cells in Type 1 Diabetes Mellitus

“…ADSCs have been used in animal models of diabetes as well as a number of human clinical trials (phase I/II) (110). Extensive clinical trials of ADSCs have been performed, and a number of these have entered phase III (39).…”