Urinary bladder smooth muscle regeneration utilizing bone marrow derived mesenchymal stem cell seeded elastomeric poly(1,8-octanediol-co-citrate) based thin films

Urinary bladder smooth muscle regeneration utilizing bone marrow derived mesenchymal stem cell seeded elastomeric poly(1,8-octanediol-co-citrate) based thin films
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DOI:
10.1016/j.biomaterials.2010.04.054
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发表时间:
2010-08-01
期刊:
影响因子:
14
通讯作者:
Cheng, Earl Y.
Cheng, Earl Y.
中科院分区:
工程技术1区
文献类型:
--
作者:
Sharma, Arun K.;Hota, Partha V.;Cheng, Earl Y.

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膀胱再生研究产生了不确定的结果,可能是由于使用不利的细胞和原始支架设计。我们假设,将人间充质干细胞接种到聚(1,8-辛二醇-共-柠檬酸盐)弹性体薄膜上将为部分膀胱再生提供合适的环境。通过使柠檬酸与1,8-辛烷磺酸反应产生POCfs,并将其接种在具有人MSC和尿路上皮细胞的相对面上:正常膀胱平滑肌细胞和UC,或未接种的POCfs。用上述POCF增强部分切除细胞的裸鼠,用网膜包裹并在4周和10周处死。分离的膀胱进行三色和抗人γ-微管蛋白,钙调蛋白,钙调蛋白,平滑肌γ-肌动蛋白,和弹性蛋白染色。POCfs的机械测试显示杨氏模量为138 kPa,伸长率为初始长度的137%,没有永久变形,表明其高单轴弹性潜力。MSC/UC POCf增强膀胱的三色和免疫荧光染色显示出典型的膀胱结构,具有肌束形成以及人源性膀胱平滑肌收缩蛋白的表达和保留。MSC/UC样品的定量形态测定显示,在10周时,肌肉/胶原蛋白比率比SMC/UC对照高约1.75倍。数据表明MSC接种的POCfs支持体内膀胱组织的部分再生。(C)2010爱思唯尔有限公司版权所有。
Bladder regeneration studies have yielded inconclusive results possibly due to the use of unfavorable cells and primitive scaffold design. We hypothesized that human mesenchymal stem cells seeded onto poly(1,8-octanediol-co-citrate) elastomeric thin films would provide a suitable milieu for partial bladder regeneration. POCfs were created by reacting citric acid with 1,8-octanediol and seeded on opposing faces with human MSCs and urothelial cells: normal bladder smooth muscle cells and UCs, or unseeded POCfs. Partial cystectomized nude rats were augmented with the aforementioned POCfs, enveloped with omentum and sacrificed at 4 and 10 weeks. Isolated bladders were subjected to Trichrome and antihuman gamma-tubulin, calponin, caldesmon, smooth muscle gamma-actin, and elastin stainings. Mechanical testing of POCfs revealed a Young's modulus of 138 kPa with elongation 137% its initial length without permanent deformation demonstrating its high uniaxial elastic potential. Trichrome and immunofluorescent staining of MSC/UC POCf augmented bladders exhibited typical bladder architecture with muscle bundle formation and the expression and retention of bladder smooth muscle contractile proteins of human derivation. Quantitative morphometry of MSC/UC samples revealed muscle/collagen ratios approximately 1.75x greater than SMC/UC controls at 10 weeks. Data demonstrate MSC seeded POCfs support partial regeneration of bladder tissue in vivo. (C) 2010 Elsevier Ltd. All rights reserved.