An Acellular Platform to Drive Urinary Bladder Tissue Regeneration

Abstract

Impaired bladder compliance secondary to congenital or acquired bladder dysfunction can lead to irreversible kidney damage. This is managed with surgical augmentation utilizing intestinal tissue, which can cause stone formation, infections, and malignant transformation. Co-seeded bone marrow mesenchymal stem cell (MSC)/CD34+ hematopoietic stem cell (HSPC) scaffolds (PRS) have been successful in regenerating bladder tissue. However, the acquisition of viable cells is challenging in the clinical setting. Here, the regenerative capacity of human MSC/CD34+ co-cultured total condition media (TCM) is compared to media alone in immune-competent rats augmented with PRS following partial cystectomy. Augmented bladders are instilled with media (control, n = 4) or TCM (n = 5) twice a week for 4 weeks. Regenerated tissue is analyzed for smooth muscle, urothelium, vascular, and peripheral nerve regrowth. Urodynamic (UDS) measures are performed pre- and 4 weeks post-augmentation. The results demonstrate that TCM-instilled grafts have greater muscle content, larger average urothelial widths, higher percent vascularization, and more robust neural infiltration post-augmentation. UDS demonstrates greater percent bladder recovery in the TCM group, indicating functional improvement in bladder storage capacity. This study is the first to propose the use of cell-free TCM as an alternative to traditional cell-seeded scaffolds to promote bladder tissue regeneration.