Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration

Sharma, A. K.; Bury, M. I.; Fuller, N. J.; Marks, A. J.; Kollhoff, D. M.; Rao, M. V.; Hota, P. V.; Matoka, D. J.; Edassery, S. L.; Thaker, H.; Sarwark, J. F.; Janicki, J. A.; Ameer, G. A.; Cheng, E. Y.

Proc Natl Acad Sci U S A. 2013 Feb 23; 110(10):4003-8

Abstract

Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we demonstrate the role of two specific populations of bone marrow (BM) stem/progenitor cells used in combination with a synthetic elastomeric scaffold that provides a unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34 hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34 grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.

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