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Discovering the process of bladder healing as the milestone for its regeneration

ABSTRACT: Molecular mechanism underlying regeneration process, triggered by stem cells in tissue engineered urinary bladder, is still poorly explained. The study aimed to explore underlining pathways associated with regeneration process in urinary bladder reconstructed with stem cell seeded graft. The study was performed on 110 Wistar rats. Urinary bladders were augmented with bladder acellular matrix (BAM)(n=52) or BAM seeded with adipose derived stem cells (ADSCs)(n=52). The process of bladder healing was analyzed at 7, 30, 90 and 180 days postoperatively. Gene expression was evaluated using microarrays and analyzed in GeneSpring Software. Gene ontology (GO) and pathway enrichment analyses of differentially expressed genes (DEGs) were performed. A total of 4023, 4674, 7997 and 1120 of DEGs between the bladders augmented with ADSCs seeded BAM and BAM only were identified at 7, 30, 90 and 180 days postoperatively, respectively. The DEGs were enriched in GO terms associated with cellular and intercellular events, morphogenesis, epithelium, smooth muscles and nerves regeneration, angiogenesis, inflammatory response and wound healing. Numerous differentially expressed pathways between the bladders augmented with ADSCs seeded BAM and BAM only were identified. In conclusion, this study provided the unequivocal evidence that stem cells changed healing milieu in tissue engineered urinary bladder and indicated underlying pathways that can be associated with regeneration process triggered by stem cells.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE103572 | GEO | 2017/09/07

SECONDARY ACCESSION(S): PRJNA401927

REPOSITORIES: GEO

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Project description:To date, there are no efficacious translational solutions for end-stage urinary bladder dysfunction. Current surgical strategies including urinary diversion and bladder augmentation enterocystoplasty (BAE) utilize autologous intestinal segments (e.g. ileum) to increase bladder capacity to protect renal function. Considered the standard of care, BAE is fraught with numerous short- and long-term clinical complications. Previous clinical trials employing tissue engineering approaches for bladder tissue regeneration have also been unable to translate bench-top findings into clinical practice. Major obstacles still persist which need to be overcome in order to advance tissue engineered products into the clinical arena. These include scaffold/bladder incongruencies, the acquisition and utlity of appropriate cells for anatomic and physiologic tissue recapitulation, and the choice of appropriate animal model for testing. Here we demonstrate that the elastomeric, bladder biomechanocompatible poly(1,8-octamethylene-citrate-co-octanol) (PRS; synthetic) scaffold co-seeded with autologous bone marrow-derived mesenchymal stem cells (MSCs) and CD34+ hematopoietic stem/progenitor cells (HSPCs) supports robust long-term, functional bladder tissue regeneration within the context of a clinically relevant baboon bladder augmentation model simulating bladder trauma. Partially cystectomized baboons were independently augmented with either autologous ileum or stem cell-seeded small intestinal submucosa (SIS; a commercially available biological scaffold) or PRS grafts. Stem cell synergism promoted functional tri-layer bladder tissue regeneration including whole graft neurovascularization in both cell-seeded grafts. However, PRS-augmented animals demonstrated fewer clinical complications and more advantageous tissue characterization metrics compared to ileum and SIS-augmented animals. Two-year study data demonstrate that PRS/stem cell-seeded grafts drive bladder tissue regeneration and are a suitable alternative to BAE.

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Discovering the process of bladder healing as the milestone for its regeneration

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