Introduction: Co-seeded mesenchymal stem cell (MSC)/CD34+ hematopoietic stem cell (HSC) citrate based scaffolds (CBS) have been successfully utilized to regenerate bladder tissue. However, the acquisition and downstream utility of these cells remains an obstacle. Here, we compare the bladder tissue regenerative capacity of the small molecule PRKR against MSC/HSC seeded CBS in a rat bladder augmentation model. Methods: Nude rats underwent an ~75% bladder cystectomy then augmented with a CBS and then 1) instilled with saline (SAL, n=7); 2) instilled with PRKR 1x/week for 2 weeks (n=7); or 3) seeded with human MSC/CD34+ HSCs (CS, n=4). Animals were sacrificed 10 weeks post-augmentation. Quantitative morphometrics was used to assess regenerated tissue with regards to muscle content, urothelium width, and vascularization via histology. Peripheral nerve regeneration was assessed by ßIII tubulin staining. Urodynamic studies (UDS) and capacity measures were performed pre- and 10 weeks post-augmentation. Results: SAL instilled animals demonstrated 24.50±2.27% muscle content while PRKR and CS instilled animals were 47.00±1.81% and 50.72±1.67% muscle content, respectively. PRKR vs SAL was p<0.0001 and CS vs SAL was p<0.0001. Urothelium width (µm) measurements demonstrated that SAL maintained a 40.82±2.15µm width where PRKR and CS constructs were 52.98±2.55 µm and 59.38±5.07µm in width, respectively. PRKR vs SAL p<0.05; CS vs SAL p<0.01. There was no statistical significance between PRKR and CS groups. Furthermore, SAL instilled animals demonstrated 1.49±0.13% vascularization while PRKR instilled and CS animals were 3.60±0.24% and 4.76±0.34% vascularization, respectively. PRKR vs SAL and CS vs SAL was p<0.0001 and PRKR vs CS groups was p<0.05. With regards to UDS, SAL instilled animals demonstrated an approximate return to pre-augmentation intravesical pressure (40cm H2O) at 10 weeks post-augmentation. PRKR instilled animals showed a decrease in pressure reaching ~25cm H2O. Similarly, CS animals returned to pre-augmentation values. Regarding percent bladder recovery, PRKR vs SAL was p<0.0001 (206.93±11.93% vs 80.28±5.61%) and CS vs SAL was p<0.0001 (111.13±2.67% vs 80.28±5.61%). There was a statistical significance between PRKR and CS groups, p<0.0001. In all studies, p<0.05 was considered statistically significant and data represents means ±SE. ßIII tubulin staining was evident in PRKR and CS groups but diminished in SAL groups. Conclusions: Data demonstrate that PRKR can be used in lieu of CS scaffolds and may also provide an alternative to bladder augmentation enterocystoplasty. SOURCE OF Funding: None
