Extracellular vesicles derived from human amniotic fluid stem cells improve bladder dysfunction in rat model of diabetic atherosclerosis

BACKGROUND The incidence of diabetic atherosclerosis (DMA) is increasing worldwide, but its pathogenesis remains incompletely understood. In addition to cardiovascular complications, bladder dysfunction is one of the common comorbidities associated with DMA but is often refractory to current treatments. AIM To investigate the therapeutic effect of human amniotic fluid stem cell-derived extracellular vesicles (hAFSC-EVs) on the recovery of bladder dysfunction in DMA rats. METHODS Eighty rats were divided into normal control, streptozotocin-induced diabetic rats, diabetic rats subjected to arterial balloon endothelial injury of common iliac artery (DMA), and DMA rats treated with hAFSC-EVs (DMA + hAFSC-EVs). At 4 weeks and 12 weeks after DMA induction, levels of blood glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, homeostasis model assessment (HOMA)-insulin resistance, and HOMA-β were measured. Cystometry, common iliac artery wall thickness, and bladder tumor necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-β1, Smad3, connective tissue growth factor (CTGF) and fibronectin were also evaluated. RESULTS Bladder weight and blood glucose, triglyceride, HOMA-insulin resistance, common iliac artery intima thickness, voided volume, intercontraction interval, bladder capacity, and mRNA expression of TNF-α , IL-6 , TGF-β1 , Smad3 , CTGF and fibronectin were significantly increased at 4 weeks and 12 weeks after induction, while the HOMA-β level decreased at 4 weeks and 12 weeks, and the high-density lipoprotein cholesterol level decreased at 12 weeks. hAFSC-EVs treatment in DMA rats significantly reduced bladder weight and blood glucose, thickness of common iliac arterial intima, voided volume, intercontraction interval and bladder capacity at 4 weeks. The mRNA expression of TNF-α , TGF-β1 , and CTGF in DMA rats treated with hAFSC-EVs were significantly decreased at 4 weeks, while the mRNA expressions of IL-6 and Smad3 were significantly decreased 12 weeks. CONCLUSION hAFSC-EVs treatment can help restore DMA-induced bladder dysfunction, which is associated with lowered blood glucose levels, reduced arterial wall thickness, and decreased TNF-α, IL-6, TGF-β1, Smad3, and CTGF expression.