Proteomic profiling of regenerated urinary bladder tissue with stem cell seeded scaffold composites in a non-human primate bladder augmentation model

Abstract

AbstractUrinary bladder insult can be caused by environmental, genetic, and developmental factors. Depending upon insult severity, the bladder may lose its ability to maintain capacity and intravesical pressures resulting in renal deterioration. Bladder augmentation enterocystoplasty (BAE) is employed to increase bladder capacity to preserve renal function using autologous bowel tissue as a “patch.” To avoid the clinical complications associated with this procedure, we have engineered composite grafts comprised of autologous bone marrow mesenchymal stem cells (MSCs) with CD34+ hematopoietic stem/progenitor cells (HSPCs) co-seeded onto a pliable synthetic scaffold [POCO; poly(1,8-octamethylene-citrate-co-octanol)] or a biological scaffold (SIS; small intestinal submucosa) to regenerate bladder tissue in a baboon bladder augmentation model. We set out to determine the protein expression profile of bladder tissue that has undergone regeneration with the aforementioned stem cell seeded scaffolds along with baboons that underwent BAE. Data demonstrate that POCO and SIS grafted animals share high protein homogeneity between native and regenerated tissues while BAE animals displayed heterogenous protein expression between the tissues following long-term engraftment. We posit that stem cell seeded scaffolds can recapitulate tissue that is almost indistinguishable from native tissue at the protein level and may be used in lieu of procedures such as BAE.Significance of StudyBladder augmentation enterocystoplasty has been used for decades as the gold-standard surgical procedure to treat severely dysfunctional bladders. Unfortunately, bowel (typically ileum) used for augmentation is an anatomical and physiological mismatch to bladder tissue and results in numerous complications including bladder perforation, secondary and tertiary redo surgeries, metabolic imbalances, excess mucus production, and increased risk of cancer. This is in part due to the intestinal protein expression that serves as a starting point and subsequent foundation in the optimization of pseudo bladder tissue. Within the context of this study, we demonstrate that autologous, bone marrow derived mesenchymal stem cells along with primitive hematopoietic stem/progenitor cells can used to regenerate bladder tissue in a large deficit, non-human primate bladder augmentation model. Data demonstrate that this synergistic cellular combination facilitates the promotion of a protein tissue landscape that is nearly identical to native bladder tissue.