Understanding the role of mesenchymal stem cells in urinary bladder regeneration - A preclinical study on a porcine model

Abstract

Background: The tissue engineering of urinary bladder advances rapidly reflecting clinical need for a new kind of therapeutic solution for patients requiring urinary bladder replacement. Majority of the bladder augmentation studies have been performed in small rodent or rabbit models. Insufficient number of studies examining regenerative capacity of tissue-engineered graft in urinary bladder augmentation in a large animal model does not allow for successful translation of this technology to the clinical setting. The aim of this study was to evaluate the role of adipose-derived stem cells (ADSCs) in regeneration of clinically significant urinary bladder wall defect in a large animal model. Methods: ADSCs isolated from a superficial abdominal Camper's fascia were labeled with PKH-26 tracking dye and subsequently seeded into bladder acellular matrix (BAM) grafts. Pigs underwent hemicystectomy followed by augmentation cystoplasty with BAM only (n = 10) or BAM seeded with autologous ADSCs (n = 10). Reconstructed bladders were subjected to macroscopic, histological, immunofluoresence, molecular, and radiological evaluations at 3 months post-augmentation. Results: Sixteen animals (n = 8 for each group) survived the 3-month follow-up without serious complications. Tissue-engineered bladder function was normal without any signs of post-voiding urine residual in bladders and in the upper urinary tracts. ADSCs enhanced regeneration of tissue-engineered urinary bladder but the process was incomplete in the central graft region. Only a small percentage of implanted ADSCs survived and differentiated into smooth muscle and endothelial cells. Conclusions: The data demonstrate that ADSCs support regeneration of large defects of the urinary bladder wall but the process is incomplete in the central graft region. Stem cells enhance urinary bladder regeneration indirectly through paracrine effect.