Regeneration of Native-Like Neo-Urinary Tissue from Nonbladder Cell Sources

Abstract

Urinary pathology requiring urinary diversion, partial or full bladder replacement, is a significant clinical problem affecting ~14,000 individuals annually in the United States alone. The use of gastrointestinal tissue for urinary diversion or bladder reconstruction/replacement surgeries is frequently associated with complications. To try and alleviate or reduce the frequency of these complications, tissue engineering and regenerative medicine strategies have been developed using bio-absorbable materials seeded with cells derived from the bladder. However, bladder-sourced cells may not always be suitable for such applications, especially in patients with bladder cancer. In this study, we describe the isolation and characterization of smooth muscle cells (SMCs) from porcine adipose and peripheral blood that are phenotypically and functionally indistinguishable from bladder-derived SMCs. In a preclinical Good Laboratory Practice study, we demonstrate that autologous adipose- and peripheral blood-derived SMCs may be used to seed synthetic, biodegradable tubular scaffold structures and that implantation of these seeded scaffolds into a porcine cystectomy model leads to successful de novo regeneration of a tubular neo-organ composed of urinary-like neo-tissue that is histologically identical to native bladder. The ability to create urologic structures de novo from scaffolds seeded by autologous adipose- or peripheral blood-derived SMCs will greatly facilitate the translation of urologic tissue engineering technologies into clinical practice.

Biofabrication and biomaterials for urinary tract reconstruction

“…Moreover, their isolation, as well as their method of culture, is well established and described liberally in the literature 101,102. However, their use may not be proper in some diseases 103. Also, harvesting cells from patients with urothelial carcinomas carries the risk of tumor recurrence 104.…”

Artificial urinary conduit construction using tissue engineering methods

“…Obtained results showed that the use of smooth muscle cells from different origins led to regeneration of a neo-organ resembling native bladder tissue composed of urothelium and smooth muscle layers. The use of acellular scaffold resulted in fibrous connective tissue development with a small number of smooth muscle cells [21]. Another study was performed on 30 rabbits using bladder acellular matrix (BAM).…”

“…Dorin et al regenerated the urethra using acellular [19,20,24]. B -two ureters were anastomosed with artificial conduit; urinary bladder was removed [21,22,23].…”

Use of regenerative tissue for urinary diversion

“…They are commonly harvested by bladder biopsy in humans and by bladder digestion in animal studies [28,32,[57][58][59]. In order to avoid a urinary source, SMCs have also been isolated from other tissues including adipose and peripheral blood [60]. In addition, as mentioned earlier, SMCs have been derived from other cells, notably MSCs [17,61 && ,62,63].…”