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

Sharma, A. K.; Hota, P. V.; Matoka, D. J.; Fuller, N. J.; Jandali, D.; Thaker, H.; Ameer, G. A.; Cheng, E. Y.

Biomaterials. 2010 May 22; 31(24):6207-17

Abstract

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 anti-human 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.

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