Benefits of mesenchymal stem cells after partial bladder outlet obstruction

Authors

  • Bader Al-Saikan University of Alberta
  • Jie Ding University of Alberta
  • Edward Tredget University of Alberta
  • Peter Metcalfe University of Alberta

DOI:

https://doi.org/10.5489/cuaj.3257

Abstract

Introduction: 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. Therefore, we hypothesize that systemic administration of MSC will demonstrate short-term biochemical, histological, and urodynamic benefits in an animal model for pBOO.

Methods: After University ethics approval, 5 x 106 green fluorescent protein GFP-labeled MSC were intravenously injected concurrently with pBOO in adult Sprague-Dawley rats. Five groups (n=3/ group) were analyzed: a) unobstructed controls; b) pBOO for seven days with intravenous MSC (7d+MSC); c) pBOO for seven days without intravenous MSC (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 reverse transcription polymerase chain reaction (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. MSC treatment resulted in a significant decrease in bladder capacity (0.91 cc vs. 2.15 cc, p=0.04). Treatment also resulted in significant decreases in mRNA levels of: TGF-B, HIF-1a, Rho-A, and GRP-78.

Conclusions: Systemic treatment with MSC was well tolerated and resulted in MSC accumulation after pBOO. Despite our low numbers, we were able to successfully demonstrate short-term urodynamic improvements and widespread, significant decreases in inflammatory mediators. We believe that this decreased inflammatory cascade will help prevent long-term detrusor deterioration.

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Author Biographies

Jie Ding, University of Alberta

Research Associate, Depratment of Surgery

Edward Tredget, University of Alberta

Professor, Department of Surgery

Peter Metcalfe, University of Alberta

Associate Professor, Department of SUrgery, University of Alberta

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Published

2016-01-14

How to Cite

Al-Saikan, B., Ding, J., Tredget, E., & Metcalfe, P. (2016). Benefits of mesenchymal stem cells after partial bladder outlet obstruction. Canadian Urological Association Journal, 10(1-2), E1–6. https://doi.org/10.5489/cuaj.3257

Issue

Section

Original Research