Human dermis-derived mesenchymal stem cells treatment is associated with glycemic improvement and immunomodulation in a streptozotocin-induced diabetic rat model

Abstract Background: Diabetes is a chronic disease with major public health concerns and high economic costs. Effective blood sugar control is essential to delay complications caused by diabetes. Objectives: This study aims to evaluate the therapeutic potential of human dermis-derived mesenchymal stem cells (hDMSCs) in streptozotocin (STZ)-induced diabetic rats. Methods: hDMSCs were isolated from human skin and characterized by cell surface and differentiation markers. hDMSCs were induced to insulin-producing cells (IPCs), and their insulin secretion was assessed. Then, hDMSCs were transplanted into STZ-induced diabetic rats through tail vein injection. Blood glucose and glycated hemoglobin (HbA1c) levels were analyzed, and the intraperitoneal glucose tolerance test (IPGTT) was performed. After the rats were sacrificed, histological staining of the pancreas and cytokine analysis in sera were performed. Results: hDMSCs expressed CD90, CD105, and CD73 and could be differentiated into chondrocytes, osteoblasts, and adipocytes. After differentiation into IPCs, they could secrete insulin upon glucose stimulation. The transplantation of hDMSCs decreased blood glucose, HbA1c, and IPGTT metrics in STZ-induced diabetic rats compared with control rats. Histological staining showed that hDMSCs were present in the pancreases of diabetic rats, indicating that hDMSCs could localize to the pancreas after transplantation, which was associated with the presence of human insulin. Serum biochemical analysis also showed increased rat insulin and decreased proinflammatory cytokines after injection with hDMSCs. Conclusion: The administration of hDMSCs is associated with significant glycemic improvement and modulation of the inflammatory microenvironment in STZ-induced diabetic rats. While these results demonstrate the therapeutic potential of hDMSCs, further studies are required to fully elucidate the underlying mechanisms of action and long-term efficacy.