Immune-Modulatory Changes After Transplantation Therapy of Insulin Producing Cells Derived from Wharton's Jelly Human Umbilical Cord-Mesenchymal Stem Cells in Diabetes Induced Rats.

Diabetes Mellitus (D.M.) is a disease with a high and increasing prevalence. The Insulin- producing Cells (IPCs) derived from the Wharton's jelly of human umbilical cord transplantation was thought to be the most promising strategy for treating Diabetes. This study aimed to evaluate IPCs immune modulatory changes occurred after transplanted through two different routes and the effect of these changes on their therapeutic efficiency in relation to transplantation microenvironment. Insulin Producing Cells was induced to differentiate from human Umbilical Cord-Mesenchymal Stem Cells and characterized by morphology under phase contrast inverted microscope and staining of secretory granules by DTZ (diphenylthiocarbonazone) stain, then therapeutic effect was evaluated both in vitro and in vivo through glucose challenge test and hyperglycemia correction in STZ (streptozotocin)- induced diabetic rats. Immune-modulatory changes evaluated by cell- mediated lysis assay and Syber green quantification of immune inflammatory cytokines (IFN- , TGF- β and IL-10) gene expression by real-time PCR. We observed that in spite of the weak immunogenicity of induced IPCs derived from HUC-MSCs in vitro, but when transplanted in vivo especially through the intra portal vein they could induce an immune response when interact with the disease microenvironment resulting in different degree of inflammatory response. Therefore, the relationship between disease microenvironment and immune alteration should be examined before transplantation therapy.