Co-transplantation of human fetal mesenchymal and hematopoietic stem cells in type1 diabetes animal model

IntroductionType 1 diabetes is an autoimmune and metabolic disease. β cell replacement is the most promising approach for type 1 diabetes but it has serious limitations. Therefore, stem cells have offered novel approaches to overcome these limitations. Several evidences, introduced different types of stem cell for treatment of various diseases such as type 1 diabetes. MSCs can be isolated from every adult or fetal tissues. Furthermore, human fetal mesenchymal and hematopoietic stem cells with various advantages seem to be ideal candidates for stem cell therapy projects. This research has focused on the co-transplantation of human fetal mesenchymal and hematopoietic stem cells in type 1 diabetes.MethodsLegally aborted fetuses were procured after obtaining informed consent. Liver from donated fetuses was cut into small pieces and disrupted and then MNCs were isolated using density gradient method. Then, isolated cells were cultured. At 2nd or 3rd subculture, the cells were prepared for characterization and transplantation. To provide animal models, a single dose Streptozotocin was injected intraperitoneally into mice. Then, animals were divided into four groups. Diabetic animals were received its predefined specific stem cells. One and 2 months after stem cell transplantation, in vivo imaging was performed to evaluate homing and engraftment sites. During the study period, blood glucose levels were measured weekly.ResultsFetal mesenchymal stem cells were positive for CD73, CD90, and CD105, but negative for CD11b, CD45, CD34, CD19, and HLA-DR. Furthermore, these cells demonstrated osteogenic, adipogenic, and chondrogenic differentiation potential. The mean of blood glucose levels were significantly reduced in group 1 and 2 that were received mixed MSCs and HSCs intravenously and intrapancreatically, in comparison with group 3 and group 4. In addition, a lot of GFP-labeled mesenchymal stem cells were engrafted in the pancreas of animal models which received a mixed suspension of HSCs and MSCs intravenously or intra-pancreatically.ConclusionWe concluded that human fetal stem cells as an alternative and valuable source for cellular therapies have some considerable advantages over their embryonic and adult counterparts. Also co-transplantation of MSCs can improve HSCs migration, engraftment, and therapeutic effects in type 1 diabetes.

Keywords:

Cell transplantation , Diabetes mellitus , Fetal stem cells , Hematopoietic stem cells , Mesnchymal stromal cells , Molecular imaging