Adipose-Derived Stem Cells and Their Derived Microvesicles Ameliorate Detrusor Overactivity Secondary to Bilateral Partial Iliac Arterial Occlusion-Induced Bladder Ischemia.

Bing-Juin Chiang,Su-Han Mao,Chun-Hou Liao,Chiang-Ting Chien

doi:10.3390/ijms22137000

Abstract

(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. Doppler 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 transcystometrogram were conducted after 2 weeks. Bladder histology, immunostaining, and lipid peroxidation 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, intercontraction interval (ICI), and bladder volume and increased the amplitude of nonvoiding contraction, 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. Inflammation, muscarinic signaling, purinergic signaling, and NGF might be involved in the therapeutic mechanism.

Highlights

Epidemiological studies have demonstrated a relationship between lower urinary tract symptoms (LUTSs) and vascular risk factors including aging, obesity, diabetes, hypertension, smoking, and hyperlipidemia [1,2]
Vascular intimal thickness on carotid Doppler ultrasonography, pelvic blood flow measured through magnetic resonance imaging, and bladder neck perfusion measured through transrectal Doppler ultrasonography have all been demonstrated to predict the severity of LUTSs [3,4,5,6]
Our results indicated that the administration of adipose-derived stem cells (ADSCs)-derived MVs through femoral artery injection significantly improved bladder microcirculation following bilateral partial iliac arterial occlusion (BPAO)

Summary

Introduction

Epidemiological studies have demonstrated a relationship between lower urinary tract symptoms (LUTSs) and vascular risk factors including aging, obesity, diabetes, hypertension, smoking, and hyperlipidemia [1,2]. Subsequent animal studies on arterial endothelial denudation techniques and high-cholesterol diets have demonstrated ultrastructural changes in the bladder, oxidative stress, nerve degeneration, inflammation, and decreased nitric oxide (NO) expression [9,10,11,12,13,14,15,16]. We observed that BPAO-induced detrusor overactivity (DO) with muscarinic and purinergic signaling changes. These results indicate that different degrees of bladder ischemia lead to various physiological and pathological changes in the bladder

Methods

Results

Discussion

Conclusion