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

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.

Adipose-derived stem cells-seeded bladder acellular matrix graft-silk fibroin enhances bladder reconstruction in a rat model

“…However, in our previous study, we only detected cells positive for both CM-DiI and α-SMA, indicating that ASCs differentiated into smooth muscle cells but not CD31 + endothelial cells [15]. Sharma et al concluded that human mesenchymal stem cells or CD34 + haematopoietic stem/ progenitor cells become incorporated into the vessel wall at the onset of neovascularization, or as pericytes in nude mice [29]. While conventional stem cell therapies focus mainly on the ability of cells to differentiate and replace damaged or injured tissue, increasing evidence suggests that stem cells also exert functional activity by secreting bioactive factors that stimulate local and systemic responses [30,31].…”

“…After the rats were euthanized by CO 2 asphyxiation, the rat bladders were excised for standard histological processing [29]. After ligating the bladder outlet by two non-absorbable 5-0 polypropylene sutures, the bladder was harvested by cutting between the two sutures.…”

Bone marrow derived cells facilitate urinary bladder regeneration by attenuating tissue inflammatory responses

“…POC [poly (1,8-octanediol-co-citrate)] was synthesized and cell seeded as previously described [15]. Athymic female rats underwent bladder augmentation as previously described in detail [15].…”

“…However, in situations where adverse pathology or reaction to a foreign body plays a pivotal role in wound healing outcomes, alternative strategies must be employed to temper over- [12,13,14]. POC [poly (1,8-octanediolco-citrate)] is an elastomeric scaffold that has demonstrated the ability to mimic mechanical properties of the bladder while providing an amenable surface for cell growth [15,16,17]. MSCs have been shown to modulate acute inflammatory responses and ameliorate injury in vivo, while CD34 + HSPCs robustly induce angiogenesis and provide support for peripheral nerve regeneration [15,18,19].…”

“…POC [poly (1,8-octanediolco-citrate)] is an elastomeric scaffold that has demonstrated the ability to mimic mechanical properties of the bladder while providing an amenable surface for cell growth [15,16,17]. MSCs have been shown to modulate acute inflammatory responses and ameliorate injury in vivo, while CD34 + HSPCs robustly induce angiogenesis and provide support for peripheral nerve regeneration [15,18,19]. Within the framework of this study, we have attempted to determine whether human bone marrow (BM) MSCs and CD34 + HSPCs combined with POC could influence the innate inflammatory response and promote bladder tissue regeneration in a rodent model of bladder augmentation.…”