Studies of tissue regeneration in a rat bladder model in vivo

Abstract

Functional integration of implanted donor tissue/organs into the host is required for the wide spread clinical success of tissue engineering/regenerative medicine technologies. To do so requires animal models that recapitulate organ/tissue development in an adult environment. As a first step in this direction, we conducted multidisciplinary investigations of bladder regeneration in female F344 rats, following removal of 60‐70% of the bladder (i.e., subtotal cystectomy; STC). Micro CT scans revealed a time‐dependent increase in bladder size (from 1‐8 wks post SCT), that was positively correlated with restoration of bladder function in vivo; despite reduced micturition pressures in vivo and diminished contractility of detrusor tissue strips in vitro. Immunohistochemistry revealed abundant c‐kit staining in the detrusor of STC rats and p63 staining in the basal layers of the urothelium. This suggests a role for stem/progenitor cells in muscle regeneration and urothelial proliferation. Innervation of the regenerated bladder was revealed by positive immunostaining to both PGP9.5 and synaptophysin. These initial studies establish the utility of this research approach as a model system for studying de novo tissue regeneration in vivo. The long‐term goal is to leverage the novel insights obtained to enhance the individual's regenerative capacity, and thus, promote maximal native tissue formation in vivo.