Differentiation Of 3D Cultured Human Mesenchymal Stem Cells Into Insulin Producing Cells And The Therapeutic Effect On Type 1 Diabetics Model Of Cynomolgus Macaque(Macaca Fascicularis)

Type 1 diabetes mellitus(T1DM)is an organ-specific autoimmune disease caused by irreversible damages to the pancreatic β cells.There is no effective cure for T1 DM yet.Mesenchymal stem cells(MSCs)have multiple differentiation potentials,unique immune regulation and paracrine ability,which provide a broad prospect for the treatment of human diseases.Studies have proven that 3D cultured MSCs have better survival ability,immune regulation and paracrine ability.Therefore,the aim of this study is to establish a 3D system for human umbilical cord derived MSCs(HUCMSCs)directional differentiate into IPCs,and to study the therapeutic effect of the IPCs evaluated by using the type 1 diabetic cynomolgus monkey model induced by streptozotocin.The specific contents include: 1)differentiate HUCMSCs into IPCs by a 3D culture systme in vitro,and identify the biological characteristics and functions of IPCs;2)establish stable type 1 diabetic cynomolgus monkey model;3)transplantate of IPCs to treat type 1 diabetic cynomolgus monkey model,and detect the effect on blood glucose regulation.Our results showed that: 1)3D cultured(human umbilical cord derived MSCs,HUCMSCs)successfully differentiated into IPCs and showed the main characteristics and functions of islet β cells;2)the results of long term monitor of fasting blood glucose,C peptide and glucose tolerance test showed that the streptozotocin stable type 1 diabetic cynomolgus monkey model was successfully established;3)after the transplantation of IPCs via hepatic portal vein,the cynomolgus monkey model showed significantly decreased level of fasting blood glucose and increased C-peptide and insulin level which maintained for several months without any immunosuppressive treatment.This study established a new method of HUCMSCs in the treatment of type 1 diabetes and paved a road for the clinical application of stem cell for patients with type 1 diabetes.