Background: Adipose mesenchymal stem cells (AMSCs) appeared as a promising therapy for type 2 diabetes (T2D). However, single AMSCs infusion could be insufficient to exert sustained antidiabetic effects. Endothelial colony forming cells (ECFCs) are implicated in various biologic processes as vascular homeostasis, neovascularization and tissue regeneration.
Aim of Work: Assessing and comparing the reparative effect of AMSCs on induced T2D rats at different time points with the potential effect of cotherapy with ECFCs.  Materials and Methods: Four rats of a total sixty adult male albino rats were used for AMSCs and ECFCs preparation and labelling with PKH26. Animals were divided into 4 main groups: I (control), II (T2D); received high fat diet for 5 weeks then received single intraperitoneal injection of STZ (40mg/kg) and continued HFD for one week. Group III (AMSCs treated) diabetic rats administered AMSCs and group IV (combined, AMSCs +ECFCs) diabetic rats received AMSCs+ECFCs. One rat from groups III and IV with their corresponded control were sacrificed 1 week after cells injection to assess homing at pancreatic tissue and the remaining rats were sacrificed after 2&6 weeks. Biochemical analysis and histological studies including H&E stain, insulin, caspase-3, CD146, Sox9 immunohistochemical stains & TEM were done followed by morphometric measurements and statistical analysis.  Results: T2D rats revealed biochemical and histological derangement in islets' β cells and vascularity with areas of stratification in pancreatic ducts. Rats treated with AMSCs only or combined with ECFCs revealed improved insulin sensitivity, glucose homeostasis and nearly normal histological features after 2 weeks. After 6 weeks biochemical and histological ameliorations regressed in AMSCs treated rats. On the contrary, cotherapy of AMSCs +ECFCs extended this anti-diabetic effect. Conclusion: ECFCs cotherapy with AMSCs prolonged and enhanced the anti-diabetic effect of AMSCs in T2D by enhancement of islets cells regeneration, islets vasculature, and probably by duct epithelium trans-differentiation.