Human Adipose Tissue-Derived Mesenchymal Stem Cells Combined With Hematopoietic Stem Cell Transplantation Synthesize Insulin

Abstract

Background Type 1 diabetes mellitus (DM) is an autoimmune disorder with disturbed glucose/insulin metabolism, which has no medical treatment other than life-long insulin therapy, despite which 30% of subjects develop organ failure. Herein we have reported the use of human adipose-tissue-derived, insulin-making mesenchymal stem cells (h-AD-MSC) transfused with unfractionated cultured bone marrow (CBM) in 5 insulinopenic DM patients. Patients and methods Five (M:F, 2:3) insulinopenic DM patients of 0.6 to 10 years' duration, ages 14 to 28 years under treatment insulin (Human with 14–70 U/d) showed postprandial blood sugars between 156 to 470 mg%, glycosylated hemoglobin 6.8% to 9.9% and c-peptide levels of 0.02 to 0.2 ng/mL. They underwent intraportal administration of xenogeneic-free h-AD-MSC (mean dose = 1.5 mL; cell counts, 2.1 × 10 3/μL). The CD45−/90+/73 + cells (29.8/16.8%) showed c-peptide levels of 3.08 ng/mL, insulin level of 1578 μIU/mL. The aliquot was supplemented with CBM (mean dose 94 mL with cell counts: 18.7 × 10 3/μL) containing CD45−/34+ elements of 0.93%. The Institutional Review Board approved the study protocol and consent forms. Results All patients were successfully infused CBM plus h-AD-MSC without any untoward effects and showed 30% to 50% decreased insulin requirements with 4- to 26-fold increased serum c-peptide levels, with a mean follow-up of 2.9 months. Conclusion This report describes safe and effective treatment of insulinopenic diabetics using insulin-producing h-AD-MSC plus CBM without xenogeneic materials.