Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California.
Department of Urology, Chaoyang Hospital, Beijing Captial Medical University, Beijing, China.
Neurourol Urodyn. 2019 Nov;38(8):2140-2150. doi: 10.1002/nau.24152. Epub 2019 Aug 27.
To investigate the possibility and mechanism of microenergy acoustic pulses (MAP) for activating tissue resident stem/progenitor cells within pelvic and urethral muscle and possible mechanism.
The female Zucker Lean and Zucker Fatty rats were randomly divided into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. MAP was applied at 0.033 mJ/mm , 3 Hz for 500 pulses, and the urethra and pelvic floor muscles of each rat was then harvested for cell isolation and flow cytometry assay. Freshly isolated cells were analyzed by flow cytometry for Pax-7, Int-7α, H3P, and EdU expression. Meanwhile, pelvic floor muscle-derived stem cells (MDSCs) were harvested through magnetic-activated cell sorting, MAP was then applied to MDSCs to assess the mechanism of stem cell activation.
Obesity reduced EdU-label-retaining cells and satellite cells in both pelvic floor muscle and urethra, while MAP activated those cells and enhanced cell proliferation, which promoted regeneration of striated muscle cells of the pelvic floor and urethral sphincter. Activation of focal adhesion kinase (FAK)/AMP-activated protein kinase (AMPK) /Wnt/β-catenin signaling pathways by MAP is the potential mechanism.
MAP treatment activated tissue resident stem cells within pelvic floor and urethral muscle in situ via activating FAK-AMPK and Wnt/β-catenin signaling pathway.
探讨微能量声脉冲(MAP)激活盆底肌和尿道肌组织驻留干细胞/前体细胞的可能性及其作用机制。
将雌性 Zucker 瘦型(ZL)和 Zucker 肥胖型(ZF)大鼠随机分为 4 组:ZL 对照组、ZL-MAP 组、ZF 对照组和 ZF-MAP 组。MAP 以 0.033mJ/mm²、3Hz 的参数施加 500 个脉冲,然后收获每组大鼠的尿道和盆底肌进行细胞分离和流式细胞术分析。通过流式细胞术分析新鲜分离的细胞中 Pax-7、Int-7α、H3P 和 EdU 的表达。同时,通过磁激活细胞分选(MACS)收获盆底肌肉源性干细胞(MDSCs),然后将 MAP 施加于 MDSCs 以评估干细胞激活的机制。
肥胖症减少了盆底肌和尿道中的 EdU 标记保留细胞和卫星细胞,而 MAP 激活了这些细胞并促进了细胞增殖,从而促进了盆底横纹肌细胞和尿道括约肌的再生。MAP 通过激活粘着斑激酶(FAK)/AMP 激活蛋白激酶(AMPK)/Wnt/β-连环蛋白信号通路来实现这一潜在机制。
MAP 治疗通过激活 FAK-AMPK 和 Wnt/β-连环蛋白信号通路原位激活盆底肌和尿道肌组织驻留干细胞。