The Therapeutic Potential Of Adipose-derived Stem Cells For Type ⅠDiabetes Mellitus

Background: Allogenic islet transplantation for type Ⅰ diabetes is limited byshortage of donor islet cells and the associated immune suppression, whilebioengineered islet-like clusters (ILCs) developed from autogenic stem cells mightbenefit those diabetic patients by their timely availability and immunorejection-freepotential as a treatment. Objectives:(1) To investingate whether humanadipose-derived stem cells (hASCs) from adult adipose tissue have the potential todifferentiate into insulin secreting, gluocose responsive and functional islet-likeclusters;(2) to develop a practical approach for islet bioengineering in vitro; and (3)to evaluate the effects of transplantation of islet-like clusters injection to cure diabeticmice. Methods: hASCs were isolated, cultured and expanded from humansubcutaneous adipose tissue. Flow cytometry analysis and multi-lineagedifferentiation were used to characterize the cultured stem cells. Conophylline, a newplant inducer, in combination with other factors were used to induce hASCs intoislet-like clusters and their effieciencies for ILCs generation were compared.Differentiated cells were identified by tissue specific surface marker staining, RT-PCRand immunocytochemistry at protein and messenger RNA level, and then, insulinsecretion of cell clusters in different glucose concentrations were tested with ELISA.Finally, the ILCs were transplanted into the abdomen of mice (Kunbai strain) withblood glucose levels≥16.65mmol/L to observe the changes of blood glucose. Results:Multipotential adipose-derived stem cells were successfully cultured and expandedfrom adult subcutaneous adipose tissues. Those stem cells were convienientlydifferentiated into glucose responsive and insulin-secreting islet-like clusters.Conophylline in combination with nicotinamide have the highest efficiency ininducing the differentiation of hASCs into islet cells. The blood glucose levels ofdiabetic mice transplanted with ILCs returned to normal within a week. Conclusion:Autogenic human adipose-derived stem cells are potentially an ideal adult cell sourcefor type I diabetes cell replacement therapy.