Engineered MSCs secreting GLP-1 enhance β-cell survival and improve glycemic control in diabetic mice.

Type 1 diabetes (T1D) arises from autoimmune destruction of pancreatic β-cells, leading to insufficient insulin production and impaired glucose regulation. Although insulin therapy and islet transplantation remain the primary treatment options, both are constrained by donor availability and the need for long-term management. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) possess notable immunoregulatory and tissue-repair properties, making them a promising candidate for cellular intervention. To further strengthen their therapeutic potential, we employed a non-viral electroporation approach to generate hUC-MSCs that stably release glucagon-like peptide-1 (GLP-1). The engineered cells were confirmed to express and secrete GLP-1 through qPCR and ELISA analyses. Conditioned medium from GLP-1-MSCs improved the survival of MIN6 β-cells exposed to oxidative injury and enhanced their glucose-responsive insulin release. In a streptozotocin-induced T1D mouse model, systemic delivery of GLP-1-MSCs reduced hyperglycemia, improved glucose and insulin tolerance, and better preserved islet architecture compared with untreated mice and those receiving unmodified MSCs. Collectively, these results indicate that electroporation-modified GLP-1-MSCs represent a safe and efficient non-viral strategy for T1D treatment and hold strong promise for future clinical application.