Combined Mesenchymal Stem Cells and Low-Energy Shock Wave Therapy Significantly Reduced Inflammation, Oxidative Stress and Preserved Podocytes in Diabetic Nephropathy

Abstract

Diabetic nephropathy (DN) is among the leading microvascular complications of diabetes mellitus and a major cause of end-stage renal disease. Current treatments slow disease progression but do not restore lost podocytes. We tested whether Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) combined with low-energy shock wave (SW) therapy could be a safe and effective therapy in a streptozotocin-induced rat model of DN. Diabetic rats received 107 WJ-MSCs together with SW (0.13 mJ/mm2, 200 shocks) once a week for five weeks. The combined regimen lowered urinary microalbumin and the albumin-to-creatinine ratio, attenuated glomerular hypertrophy, and reduced fibronectin and collagen I deposition. Podocyte markers (WT-1, synaptopodin, nephrin) recovered toward normal levels. WJ + SW therapy suppressed NF-κB and IL-6 while raising IL-4 and IL-10, lowered NOX4 expression, and increased the antioxidant enzyme HO-1. Renal macrophages also shifted from the pro-inflammatory M1 phenotype to the reparative M2 phenotype. Together, these findings indicate that combining WJ-MSCs with low-energy SW therapy acts on multiple pathogenic axes of DN and may offer a potential interventional strategy for this inescapable and progressive complication.