Pharmacologic response of regenerated bladders in a preclinical model

Abstract

PurposeNeo‐bladder pharmacology was evaluated in animals after total cystectomy and implant of Autologous Neo‐Bladder Replacement constructs (NBR) made from bladder smooth muscle cells (SMC).MethodsNBR were seeded with SMC to form three test groups in which 25, 12, or 4x106 SMC were seeded per construct (n= 8/grp). A fourth group (n=8) in which radically cystectomized bladders were immediately reimplanted (R) served as a control. Ex‐vivo pharmacological and histological studies were conducted on neo‐bladder tissues at study termination.ResultsAt 9 mo post‐implantation, neo‐bladders of all groups had tissue histology (including mucosal and serosal linings, detrusor muscle, vasculature, and nerve components) consistent with native bladder. Contractile responses to parasympathomimetic (carbachol) and sympathomimetic (phenylephrine) agonists were similar among all groups. Logistic analysis of bladder tissue strips subjected to electrical field stimulation (EFS) revealed similar EC50 and slope factor values for all groups.ConclusionsAn Autologous Neo‐bladder Replacement construct is capable of regenerating a complete urinary bladder as a total organ with structural, urodynamic, and pharmacological features similar to native bladder. There was no evidence of abnormal tissue development, immune response, or systemic response to the neo‐bladder regeneration in any group.