• Bing-Juin Chiang, Su-Han Mao, Tung-Sheng Chen, Shiu-Dong Chung, and Chiang-Ting Chien.
• College of Medicine, Fu-Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City, 24205, Taiwan; Department of Urology, Cardinal Tien Hospital, No.362, Zhongzheng Rd., Xindian Dist., New Taipei City, 23148, Taiwan; Department of Life Science, College of Science, National Taiwan Normal University, 162, Section 1, Heping E. Rd., Taipei, 106, Taiwan.
• J Formos Med Assoc. 2024 Dec 9.

Background/PurposeThe mechanism for long-term hypoxia/ischemia induced bladder underactivity is uncertain. It requires an effectively therapeutic treatment. Therefore, we determined the pathophysiologic mechanisms of long-term bilateral partial iliac arterial occlusion (BPAO)-induced bladder underactivity and explored the therapeutic potential of adipose-derived stem cells (ADSCs) and ADSC-derived microvesicles (MVs) on BPAO-induced bladder dysfunction.MethodsThe study included four groups: sham, BPAO, BPAO + ADSCs, and BPAO + ADSC-MVs. ADSCs or ADSC-MVs were isolated, characterized with specific CD markers and injected through the femoral artery to the rat bladders. Real-time laser speckle contrast imaging evaluated bladder microcirculation after BPAO. The transcystometrogram, pelvic nerve activity, bladder histology, immunohistochemistry, and lipid peroxidation assays were conducted after 4-week BPAO induction. The molecular mechanisms of bladder expression of purinergic P2X2/P2X3 and cholinergic M2/M3 receptors for regulating bladder contractility, nerve growth factor (NGF) for nerve injury repair, and collagen-1 for fibrosis were evaluated.ResultsLong-term BPAO significantly reduced bladder microcirculation, prolonged the intercontraction interval, decreased voiding volume, increased residual urine volume, lengthened phase 1 contraction, shortened phase 2 contraction, increased leukocytes and CD68 infiltration, increased malondialdehyde levels, and decreased levels of P2X3 and M3 receptors. ADSC-MVs were more efficient than ADSCs in improving BPAO induced parameters, recovering P2X3 and M3 receptors, increasing NGF expression, and decreasing collagen-1 expression in the bladder.ConclusionsADSC-derived MVs were better than ADSCs to improve long-term BPAO-induced detrusor underactivity, bladder ischemia, and oxidative stress. ADSC-MVs through the therapeutic action of ameliorating inflammation, improving purinergic/cholinergic signaling and neuronal regeneration, and decreasing fibrosis improved BPAO-induced bladder underactivity.Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

6 keywords...

hide…