Bone marrow mesenchymal stem cells (BMSCs) have shown the properties of immunosuppression and low immunogenicity and the potential capacity for differentiating into pancreatic islet-like cell clusters containing insulin-producing cells (PICs),thus being a valuable cellular source for pancreatic islets regeneration.However,the formation rates of the pancreatic islet-like cell clusters are low under adherence induction.We developed a chemically defined induction procedure under suspension to differentiate the human first-trimester fetal BMSCs (hfBMSCs) towards PICs in plastic dishes without any coating and reached a cluster formation rate of 78.6±9.4%.The differentiated clusters were stained into crimson with Dithizone and contained 65.3±13.3% PICs,which expressed broad gene profile related to pancreatic islet cells and released insulin (2.945±0.487pmol/100 clusters/30 min) and C-peptide (2.831±0.367pmol/100 clusters/30 min) under high glucose stimulus in vitro.And the blood glucose levels of STZ-induced diabetic model mice were normalized for at least 80 days following the xenograft with the induced clusters but rose back to pathogenic levels after the removal of the grafts.A series of examination of the grafts indicated that the transplanted cells survived in recipients and produced human insulin in situ.In conclusion,hfBMSCs are the great advantage of the potential cell source for the treatment of diabetes and suspension induction can promote their clustering,differentiation towards IPCs and survival.