Adipose-derived stem cell-derived microvesicles prevent progression to bladder underactivity secondary to long-termed bilateral partial iliac arterial occlusion-induced bladder ischemia

Background The therapeutic effects of adipose-derived stem cells (ADSCs) and ADSC-derived microvesicles (MVs) were investigated in a rat model of bladder ischemia involving long-term (4 weeks) bilateral partial iliac arterial occlusion (BPAO). Methods The study included four groups: sham, BPAO, BPAO + ADSCs, and BPAO + ADSC-derived MVs. ADSCs or ADSC-derived MVs were injected through the femoral artery. Real-time laser speckle contrast imaging evaluated bladder microcirculation following BPAO. A 24-h behavior study and transcystometrogram were conducted after 4 weeks. Bladder histology, immunostaining, and lipid peroxidation assays were performed. The expression of P2X2, P2X3, M2, and M3 receptors, nerve growth factor (NGF), and collagen-1 was evaluated. Results BPAO for 4 weeks significantly reduced bladder microcirculation, prolonged the intercontraction interval, decreased voiding volume, increased residual urine volume, lengthened phase 1 contraction, shortened phase 2 contraction, increased neutrophil infiltration, increased malondialdehyde levels, and altered levels of P2X3 receptors. ADSC-derived MVs significantly ameliorated these effects, increased NGF expression, and decreased collagen-1 expression. ADSCs only improved voiding volume and increased residual urine volume. Conclusions ADSC-derived MVs prevented adverse consequences of long-term BPAO, including detrusor underactivity, bladder ischemia, and oxidative stress. Amelioration of inflammation, altered purinergic signaling, neuronal regeneration, and decreased fibrosis might be involved in the therapeutic mechanism.