Engineering Placental Mesenchymal Stem Cells with PEDF for Retinal Protection in Diabetic Retinopathy

Diabetic retinopathy (DR) is a major cause of adult blindness and is characterized by progressive retinal vascular dysfunction and pathological angiogenesis. To establish a DR model, streptozotocin (STZ) was intraperitoneally injected into rats. After 8 weeks, naïve placenta-derived mesenchymal stem cells (PD-MSCs) or PEDF-overexpressing PD-MSCs (PD-MSCs^PEDF) were intravitreally transplanted into the right eye for 4 weeks. Pathological neovascularization in DR is regulated by the balance between vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). In diabetic retinas, increased VEGF and decreased PEDF expression were reversed following PD-MSC transplantation. Notably, PD-MSCs^PEDF treatment resulted in higher PEDF, and lower VEGF expression compared with naïve PD-MSCs, with similar expression patterns observed in the contralateral non-transplanted eyes. These findings indicate that engineering PD-MSCs^PEDF enhances anti-angiogenic activity by modulating VEGF and PEDF balance, thereby alleviating vascular damage in STZ-induced diabetic retinas.