Transplantation routes affect the efficacy of human umbilical cord mesenchymal stem cells in a rat GDM model

Abstract

Gestational diabetes mellitus (GDM) is harmful to both the mother and fetus. Although transplantation of human umbilical cord mesenchymal stem cells (HUMSCs) could be a useful therapy for GDM, the influences of different transplantation routes on the therapeutic effects remain unclear. In this study, we isolated and cultured the HUMSCs for transplantation, and the biological activity of HUMSCs was verified by flow cytometric analysis (the positive markers, CD44, CD73, CD105 and CD90, the negative markers, CD45, CD34, CD19, HLA-DR, and CD11b) and potency of osteogenic, adipogenic and chondrogenic differentiation. Streptozotocin (STZ)-induced diabetes mellitus (DM)/GDM rats were transplanted with HUMSCs by different routes: single or multiple tail vein injection, liver parenchyma, and renal capsule transplantation. These were compared to positive controls (STZ-induced, untreated) and negative controls (non-induced, untreated) to determine the effect of the transplant on the control of DM/GDM. The blood glucose level and body weight of rats in each group were determined and showed different effects. Transplantation of HUMSCs to GDM rats can increase the number of offspring in comparison to the negative controls. The weight of the offspring in the transplantation groups also increased due to the therapeutic effect of HUMSCs. Based on results, we concluded that transplanting HUMSCs could effectively alleviate the symptoms of elevated blood glucose and weight loss and improve the body weight and survival rate of offspring. Injections of HUMSCs were required to persistently decrease the blood glucose of DM and GDM rats. Transplanting HUMSCs into the liver or renal capsule of GDM rats led to a similar efficiency of controlling blood glucose and compensation for body weight. HUMSCs therapy increased the number and body weight of offspring and improved their activity. In summary, this study has enabled progress toward determining the optimal route for GDM therapy.

Keywords: Gestational diabetes mellitus; Human umbilical cord; Mesenchymal stem cells; Streptozotocin; Transplantation.