Impact of parturition on chemokine homing factor expression in the vaginal distension model of stress urinary incontinence, "Beyond the Abstract," by Andrew T. Lenis, BS; Hadley M. Wood, MD; and Margot S. Damaser, PhD

BERKELEY, CA (UroToday.com) - While invasive surgical treatments for stress urinary incontinence (SUI) demonstrate long-term efficacy, minimally invasive options, such as endoscopic injection of bulking agent, fail to provide durable results.[1, 2] Several pre-clinical and preliminary clinical data suggest that endoscopic injection of autologous muscle-derived progenitor cells may become the next minimally invasive option.[3, 4] The hope is that progenitor/stem cells will provide durable results via the actions of cellular differentiation and/or the secretion of paracrine factors that promote cell growth, neovascularization, and tissue healing.

Progenitor/stem cell treatment for SUI may aid recovery by mimicking an endogenous repair process that occurs following trauma to the continence structures during vaginal childbirth. This process has been studied in animals via functional and histologic outcomes, stem cell homing factor expression, and stem cell migration and differentiation in rats undergoing vaginal distension (VD), a purely mechanical model of human childbirth injury.[3, 5, 6, 7] The effect of pregnancy and parturition on these outcomes, however, was largely unknown. Therefore, it was the goal of our study to help elucidate this natural process of repair following vaginal childbirth to better inform treatment strategies using stem cells and stem cell-based products.

Our results, supported by others’ previous data, suggest that pregnancy and parturition largely modulate the biochemical response to simulated human childbirth by affecting the mechanical properties (i.e., distensibility) of the pelvic tissues.[8] Independently, pregnancy and parturition did have an effect on CD191, one of several receptors for the stem cell homing cytokine CCL7. The mechanical trauma of VD, on the other hand, affected the expression of all other chemokines and receptors assayed.

As it is currently being studied, progenitor/stem cell treatment for SUI involves a muscle biopsy, off-site isolation and expansion of autologous progenitor cells, and then a second procedure for endoscopic periurethral injection of these cells. Ideal treatment would identify at-risk women early in disease progression, utilize “off-the-shelf” progenitor/stem cells or cell-free based products, and harness stem cell homing to the urethral sphincter and other damaged pelvic tissues.

Much additional research is required to bring the ideal progenitor/stem cell therapy for SUI to the bedside, including:

  1. Improved understanding and delineation of mechanical vs hormonal contributions to the pathophysiology
  2. Identification of progenitor/stem cell products that halt or reverse the aforementioned pathophysiologic process
  3. Ability to manufacture these products using allogenic progenitor/stem cells to limit the time between cell harvest and treatment
  4. Method to optimize stem cell homing, even years after childbirth
  5. Appropriately controlled prospective clinical trials

As in many other fields, stem cells and regenerative medicine will likely play a larger role in the care of women with various pelvic floor disorders, including SUI.

 

References:

  1. Funk MJ, Siddiqui NY, Kawasaki m et al. Long-Term Outcomes After Stress Urinary Incontinence Surgery. Obstet Gynecol 2012; 120: 83.
  2. Rovner ES, Wein AJ. Treatment Options for Stress Urinary Incontinence. Rev Urol 2004; 6: S29.
  3. Dissaranan C, Cruz MA, Gill BC et al. Intravenous Mesenchymal Stem Cells Home to the Urethra and Facilitate Recovery from Stress Urinary Incontinence after Childbirth Injury via Secretion of Paracrine Factors. J Urol 2011; 185: e73.
  4. Peters K, Kaufman MR, Dmochowski R et al. Autologous muscle derived cell therapy for the treatment of female stress urinary incontinence: a multi-center experience. J Urol 2011; 185: e535.
  5. Cruz MA, Dissaranan C, Cotleur A et al. Pelvic Organ Distribution of Mesenchymal Stem Cells Injected Intravenously after Simulated Childbirth Injury in Female Rats. Obstet Gynecol Int 2012; 2012: 612946.
  6. Woo LL, Hijaz A, Kuang M et al. Over expression of stem cell homing cytokines in urogenital organs following vaginal distention. J Urol 2007; 177: 1568.
  7. Wood HM, Kuang M, Woo L et al. Cytokine expression after vaginal distention of different durations in virgin Sprague-Dawley rats. J Urol 2008; 180: 753.
  8. Lowder JL, Debes KM, Moon DK et al. Biomechanical adaptations of the rat vagina and supportive tissues in pregnancy to accommodate delivery. Obstet Gynecol 2007; 109: 136.

 

Written by:
Andrew T. Lenis, BS;1, 2 Hadley M. Wood, MD;3 and Margot S. Damaser, PhD2, 3 as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

1 Case Western Reserve University School of Medicine
2 Department of Biomedical Engineering, Cleveland Clinic
3 Glickman Urological and Kidney Institute, Cleveland Clinic Cleveland, Ohio

Impact of parturition on chemokine homing factor expression in the vaginal distension model of stress urinary incontinence - Abstract

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