Maturation and growth of the bladder wall in a rodent model of organ regeneration

Abstract

We previously established a model of organ regeneration in which the rodent bladder regenerates to the original volume after subtotal cystectomy (STC; removal of ~70% of the bladder). In this study, we further examined the growth and maturation of the bladder wall over time from 1–8 weeks post‐STC. Female F344 rats underwent STC with age‐matched control rats run in parallel. MRI scans revealed a thinner bladder wall 1 week post‐STC (281.96 μM) compared to pre‐STC levels (493.53 μM) that improved greatly by 8 weeks (427.76 μM). In vivo urodynamics revealed bladder hyperactivity after afferent nerve activation via intravesical administration of 30 μM capsaicin. Vesicular acetylcholine transporter staining demonstrated the presence of motor nerves. Immunohistochemistry for proliferating cell nuclear antigen revealed proliferating cells 1, 2, and 4 weeks post‐STC. Uroplakin 3 staining showed mature urothelial cells 1 week post‐STC. Positive immunostaining was also observed for smooth muscle alpha actin, myosin heavy chain and desmin; with the greatest staining closest to the plane of excision. These studies establish that regeneration of the urinary bladder involves regeneration of both sensory and motor nerves with progressive maturation of the bladder wall. The goal of these studies is to uncover the mechanistic basis of bladder regeneration in adult mammals and use this knowledge for clinical applications.