Intramuscular Stem Cell Transplant Restores Pancreatic Function in Diabetic Mice

Type 1 Diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing pancreatic beta cells, leading to lifelong insulin dependence. Current treatments, primarily exogenous insulin, manage symptoms but do not cure the disease or prevent long-term complications. Pancreatic islet transplantation offers a potential cure but is limited by donor scarcity and the need for immunosuppression. Human pluripotent stem cells (hPSCs) represent a promising, scalable source for generating functional pancreatic endocrine cells. However, finding an optimal, accessible, and safe transplantation site remains a challenge. This study addresses the knowledge gap of evaluating the efficacy and safety of intramuscular transplantation as a novel delivery route for hPSC-derived pancreatic endocrine cells.

Intramuscular transplantation of hPSC-derived pancreatic endocrine cells significantly improved glucose homeostasis in diabetic mice. Treated mice showed a sustained reduction in fasting blood glucose levels, decreasing from an average of 350 mg/dL pre-treatment to 120 mg/dL by week 8, compared to control mice which remained hyperglycemic at 380 mg/dL (p<0.001). Histological analysis confirmed the successful engraftment and vascularization of the transplanted cells within the muscle, forming well-differentiated islet-like structures expressing insulin and glucagon. Glucose tolerance tests revealed that treated mice exhibited significantly improved glucose clearance, with an AUC (Area Under the Curve) reduction of 65% compared to controls (p<0.001). The most significant finding was the detection of robust human C-peptide secretion in the serum of treated mice, indicating functional insulin production from the transplanted cells, with levels reaching 2.5 ng/mL by week 12, a 10-fold increase over baseline and undetectable levels in controls (p<0.0001).