Abstract
Engineered bladder tissues, created with autologous bladder cells seeded on biodegradable scaffolds, are being developed for use in patients who need cystoplasty. However, in individuals with organ damage from congenital disorders, infection, irradiation, or cancer, abnormal cells obtained by biopsy from the compromised tissue could potentially contaminate the engineered tissue. Thus, an alternative cell source for construction of the neo-organ would be useful. Although other types of stem cells have been investigated, autologous mesenchymal stem cells (MSCs) are most suitable to use in bladder regeneration. These cells are often used as a cell source for bladder repair in three ways - secreting paracrine factors, recruiting resident cells, and trans-differentiation, inducing MSCs to differentiate into bladder smooth muscle cells and urothelial cells. Adult stem cell populations have been demonstrated in bone marrow, fat, muscle, hair follicles, and amniotic fluid. These cells remain an area of intense study, as their potential for therapy may be applicable to bladder disorders. Recently, we have found stem cells in the urine and the cells are highly expandable, and have self-renewal capacity and paracrine properties. As a novel cell source, urine-derived stem cells (USCs) provide advantages for cell therapy and tissue engineering applications in bladder tissue repair because they originate from the urinary tract system. Importantly, USCs can be obtained via a noninvasive, simple, and low-cost approach and induced with high efficiency to differentiate into bladder cells.
Highlights
Stem cell-based therapy for bladder repair is most relevant to congenital bladder conditions or conditions such as radiation damage, infection, interstitial cystitis, neuropathic small bladder disease, and bladder cancer
We recently found that a subpopulation of cells isolated from urine possess biological characteristics similar to Mesenchymal stem cell (MSC); that is, clonogenicity, cell growth patterns, expansion capacity [15,35], cell surface marker expression profiles [15], multipotent differentiation capacity [16,36,37,38,39,40], pro-angiogenic paracrine effects [41,42], immunomodulatory properties [43] and induced Induced pluripotent stem cell (iPSC) [44]
We found that Urine-derived stem cell (USC) differentiate into cells of the endothelial lineage when grown in endothelial differentiation medium containing 2 ng/ml vascular endothelial growth factor (VEGF) for 12 days [15]
Summary
Stem cell-based therapy for bladder repair is most relevant to congenital bladder conditions (for example, bladder exstrophy) or conditions such as radiation damage, infection, interstitial cystitis, neuropathic small bladder disease, and bladder cancer. Several methods might help reach this goal: (i) using biomaterials with a porous micro-structure that might protect cell retention within the scaffold; (ii) keeping the cell-seeding scaffold construct wet in the culture media, and avoid drying it out during surgery; (iii) inducing angiogenesis or capillary network formation early in implantation with angiogenic growth factors released from microbeads or binding scaffolds in the site or using hypoxia as a pretreatment for implanted cells; and (iv) promoting revascularization (artery-capillary-venous system) at the mid or late stage after the implantation with biologically safe physical stimulation, including lower-frequency electrical stimulation or low-intensity ultrasound These methods could extend the lifespan of implanted cells in vivo to provide better tissue repair with long-term release of paracrine factors and trans-differentiation, anti-fibroblast formation, and antiinflammatory and anti-apoptotic effects of MSCs. In addition, innervation is critical to create a functional bladder.
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