(1) Background: We established a new bladder ischemia rat model through bilateral partial iliac arterial occlusion (BPAO) and investigated the therapeutic effect of adipose‐derived stem cells (ADSCs) and ADSC‐derived microvesicles (MVs); (2) Methods: The study included four groups: (1) sham, (2) BPAO, (3) BPAO + ADSCs, and (4) BPAO + ADSC‐derived MVs. Female Wistar rats with BPAO were injected with ADSCs or ADSC‐derived MVs through the femoral artery. Dop-pler flowmetry and real‐time laser speckle contrast imaging were performed to quantify blood flow in the common iliac arteries and bladder microcirculation. A 24‐h behavior study and transcysto-metrogram were conducted after 2 weeks. Bladder histology, immunostaining, and lipid peroxida-tion assay were performed. The expressions of P2X2, P2X3, M2, and M3 receptors and nerve growth factor (NGF) were evaluated; (3) Results: BPAO significantly reduced bladder microcirculation, in-tercontraction interval (ICI), and bladder volume and increased the amplitude of nonvoiding con-traction, neutrophil infiltration, and malondialdehyde and NGF levels. ADSCs and ADSC‐derived MVs significantly ameliorated these effects. The results of Western blot showed that the BPAO group exhibited the highest expression of M3 and P2X2 receptors. ADSCs significantly attenuated the expressions of M2 and P2X2 receptors. ADSC‐derived MVs significantly attenuated the expressions of M3 and P2X2 receptors; (4) Conclusions: ADSCs and ADSC‐derived MVs ameliorated the adverse effects of BPAO including bladder overactivity, bladder ischemia, and oxidative stress. In-flammation, muscarinic signaling, purinergic signaling, and NGF might be involved in the therapeutic mechanism.
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