Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells

AIM:To explore the possibility of marrow mesenchymalstem cells(MSC)in vitro differentiating into functional islet-like cells and to test the diabetes therapeutic potency ofIslet-like cells.METHODS:Rat MSCs were isolated from Wistar rats andcultured.Passaged MSCs were induced to differentiate intoislet-like cells under following conditions:pre-induction withL-DMEM including 10 mmol/L nicotinamide l mmol/Lβ-mercaptoethanol 200 mL/L fetal calf serum(FSC)for 24 h,followed by induction with serum free H-DMEM solution including10 mmol/L nicotinamide l mmol/L,β-mercaptoethanol for10 h.Differentiated cells were observed under inversemicroscopy,insulin and nestin expressed in differentiatedcells were detected with immunocytochemistry.Insulinexcreted from differentiated cells was tested withradioimmunoassay.Rat diabetic models were made to testin vivo function of differentiated MSCs.RESULTS:Typical islet-like clustered cells were observed.Insulin mRNA and protein expressions were positive indifferentiated cells,and nestin could be detected in pre-differentiated cells.Insulin excreted from differentiatedMSCs(446.93±102.28 IU/L)was much higher than thatfrom pre-differentiated MSCs(2.45±0.81 IU/L(P<0.01).Injected differentiated MSCs cells could down-regulateglucose level in diabetic rats.CONCLUSION:Islet-like functional cells can be differentiatedfrom marrow mesenchymal stem cells,which may be anew procedure for clinical diabetes stem-cell therapy,thesecells can control blood glucose level in diabetic rats.MSCsmay play an important role in diabetes therapy by isletdifferentiation and transplantation.