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The Anti-Inflammatory Effect of Mesenchymal Stem Cells after Partial Bladder Outlet Obstruction
Peter Metcalfe, MD, MSc, FRCSC, Bader Al-Saikan, MD, PhD, Jie Ding, MD, PhD, Edward Tredget, MD,FRCSC.
University of Alberta, Edmonton, AB, Canada.

Background: Partial bladder outlet obstruction (pBOO) results in significant morbidity and mortality in the pediatric and adult populations. Mesenchymal stem cells (MSC) have been widely studied in many organ systems for the treatment and prevention of fibrotic and inflammatory conditions. Through our animal model, we have previously demonstrated that bladders progress from an initial inflammatory response, then smooth muscle hypertrophy, and finally fibrosis after pBOO. Therefore, we hypothesize that systemic administration of MSC will demonstrate short-term biochemical, histologic, and urodynamic benefits in an animal model for partial bladder outlet obstruction (pBOO).
Methods: After University ethics approval, 5x106 GFP labeled, commercially acquired, MSC were injected via tail vein at the time of pBOO. 15 rats were divided into 5 groups: a) unobstructed controls, b) PBOO for 7 days with intravenous MSC (7d +MSC), c) pBOO for 7 days without (7d-MSC), d) pBOO for 14 days with intravenous MSC (14d+MSC), e) pBOO for 14 days without MSC (14d- MSC). Urodynamics were performed at the end of the experimental period and bladders were weighed. Immunohistochemistry was performed for GFP detection and RT-PCR to detect mRNA of: TGF-B, HIF-1a, RhoA, GRP-78, lumican, and decorin.
Results: All animals remained healthy. GFP was detected in all treatment groups. There was no significant difference in bladder weights or urodynamic pressures. However, MSC treatment resulted in a significant decrease in bladder capacity in the 14d+MSC group (0.91 cc vs. 2.15 cc, p=0.04), which resulted in capacities similar to unobstructed controls. MSC treatment also resulted in a decrease in mRNA levels of: TGF-B, HIF-1a, Rho-A, GRP-78. However, no differences were seen in levels of SLRPs lumican or decorin.
Conclusion: Systemic treatment with MSC was well tolerated and resulted in MSC in the bladder after pBOO. We demonstrated short-term urodynamic improvements, whereby treated animals did not show the increase in capacity normally seen after pBOO. There was a widespread and significant decrease in inflammatory mediators which we have previously shown to be prominent in the progression to fibrosis after pBOO. We believe that this may speak to a significant role of MSC in decreasing inflammation and potentially preventing long-term damage.

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