Age‐dependent Impairments in Rat Bladder Regeneration

Abstract

Models of de novo organ regeneration in mammals may provide guidance for harnessing natural regenerative capacities. We previously reported that removal of ~70% of the bladder (subtotal cystectomy; STC) in 12 week old female rats induces regeneration leading to functional recovery. In this study, 12 month (“older”) and 12 week (“younger”) old female rats underwent STC, and were followed up to 26 wks post‐STC with in vivo urodynamics, and pharmacological and histological analysis ex vivo. STC in older animals led to a higher mortality/morbidity rate (26%) than younger animals (11%), with histologic evidence of kidney damage. Bladder capacity 26 weeks post‐STC was 56% of age‐matched controls (AMC) in older rats, and 96% of AMCs in younger rats. There was no significant residual volume found in any group. Responses of bladder strips to several physiologically relevant stimuli were lower in younger STC animals than those from control bladders, but higher than older STC animals. Histology revealed age‐related differences post‐STC with respect to inflammation, angiogenesis, fibrosis, and proliferation. The impaired regeneration observed in older animals stands in stark contrast to the rather complete regeneration observed in younger animals. As such, this rodent model may aid in elucidating the basic biology of mammalian organ regeneration and identifying targetable pathways for optimizing regenerative capacity.