MicroRNA-126 from stem cell extracellular vesicles encapsulated in a tri-layer hydrogel scaffold promotes bladder angiogenesis by activating CXCR4/SDF-1α pathway
MicroRNA-126 from stem cell extracellular vesicles encapsulated in a tri-layer hydrogel scaffold promotes bladder angiogenesis by activating CXCR4/SDF-1α pathway
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DOI：
10.1016/j.cej.2021.131624
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发表时间：
2021-08
影响因子：
15.1
通讯作者：
D. Xiao;Mengbo Yang;Ming Zhang;Liduo Rong;Yamei Wang;Huan Cheng;X. Sui;S. Sheikh;Mujun Lu
中科院分区：
文献类型：
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作者：
D. Xiao;Mengbo Yang;Ming Zhang;Liduo Rong;Yamei Wang;Huan Cheng;X. Sui;S. Sheikh;Mujun Lu
由于防水性和抗拉伸性不足，水凝胶在膀胱壁再生中的应用很少。设计了一种由膀胱脱细胞基质移植物-海藻酸二醛-明胶水凝胶-丝网（BAMG-HS）组成的三层水凝胶支架，用于包封人脂肪干细胞（ASCs）来源的细胞外囊泡（EVs），旨在促进膀胱再生。在大鼠膀胱增强模型中评估促血管生成复合生物材料，其中大鼠随机分为BAMG-HS- evs组（分别在2、4和12周取样n = 6）、BAMG-HS组（n = 6、12周）和假手术对照组（n = 6、12周）。三层水凝胶支架具有优异的机械性能和可生物降解性能，促进血管生成，促进尿路上皮、平滑肌和神经纤维的膀胱形态再生，功能恢复，无明显纤维化或炎症失调。人ascs - ev激活膀胱CXCR4/SDF-1α通路，增强人脐静脉内皮细胞（HUVEC）的增殖、侵袭性和管状结构形成。它们被HUVEC内化后，上调microRNA-126，抑制RGS16，激活CXCR4/SDF-1α通路，从而增强VEGF分泌通过aerk1 /2磷酸化。
Restricted by insufficient waterproofness and stretching resistance, hydrogel alone is seldomly applied in bladder wall regeneration. A tri-layer hydrogel scaffold comprising bladder acellular matrix graft-alginate di-aldehyde-gelatin hydrogel-silk mesh (BAMG-HS) was designed to encapsulate human adipose stem cells (ASCs)-derived extracellular vesicles (EVs), aiming to facilitate bladder regeneration. The proangiogenic composite biomaterial was evaluated in a rat model of bladder augmentation, where rats were randomly allocated to BAMG-HS-EVs (n = 6 sampled at 2, 4, and 12 weeks, respectively), BAMG-HS (n = 6, 12 weeks) and sham operation control groups (n = 6, 12 weeks). The tri-layer hydrogel scaffold has excellent mechanical and biodegradable properties, promotes angiogenesis and facilitates bladder morphological regenerations of urothelium, smooth muscle and neural fibers, and functional restoration without unmitigated fibrosis or dysregulated inflammation. Human ASCs-EVs activate bladder CXCR4/SDF-1α pathway, and enhance human umbilical vein endothelial cells (HUVEC) proliferation, invasiveness and tube-like structure formation. After internalization by HUVEC, they up-regulate microRNA-126 and inhibit RGS16 to activate CXCR4/SDF-1α pathway, thus enhancing VEGF secretionviaERK1/2 phosphorylation.