Nonhuman Primate Model of Bladder Regeneration Using Autologous Bone Marrow Cells

PROJECT SUMMARY/ABSTRACT Patients with a pathologic bladder have chronic medical problems with urinary incontinence, infections, and potential renal failure. Conventional surgical management of the pathologic bladder uses detubularized bowel as a patch (enterocystoplasty) to enlarge the bladder. Although enterocystoplasty provides functional improvement, it is associated with significant short- and long-term complications. Thus, alternative methods to enterocystoplasty have been explored through tissue engineering by seeding cultured bladder cells on bioscaffolds as an augmentation patch. With these techniques, marginal success has been noted but regeneration of fully functional normal bladder tissue has yet to be achieved. Several obstacles currently limit advancement in this research field including the choice of a relevant animal model; appropriate cell types for seeding, adequate neovascularization of the seeded graft, tissue innervation, and primitive bioscaffold design. Thus, alternative cell sources, advancements in bioscaffold design, and applicable animal models are needed to address these unmet clinical needs. Bone marrow stem/progenitor cells (BMSPCs) represent a highly defined population of cells that are easily accessible and may be used for bladder regeneration. BMSPCs are non-exclusively comprised of mesenchymal stem cells (MSCs) and hematopoietic stem/progenitor cells (HSPCs). MSCs have been shown to be capable of smooth muscle cell (SMC) differentiation and are involved in the bladder regenerative process, while HSPCs have demonstrated the ability to facilitate the growth of new blood vessels in regenerating tissue while aiding in peripheral nerve and urothelium regeneration. Recent developments in elastomer chemistry and scaffold design have allowed for the development of synthetic scaffolds that have controlled kinetic release of growth factors that are important for the regenerative process and that can mimic the mechanical properties of the