Potential Role Of Stem Cells In The Treatment Of Incontinence And Pelvic Prolapse

Main Category: Urology / Nephrology
Also Included In: Stem Cell Research;  Women's Health / Gynecology
Article Date: 02 Jul 2008 - 8:00 PDT

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ORLANDO, FL (UroToday.com) - The potential role of stem cells in the treatment of incontinence and pelvic prolapse has been a subject of much attention. A group from Torrance, CA reported on their promising experience using muscle derived stem cells (MDSC) grown on scaffolds of small intestinal submucosal (SIS) to stimulate repair of the vaginal wall in rats (Abstract #1369). The group demonstrated that MSDCs differentiate into smooth muscles cells in vitro, that specific, detectable markers are expressed from these cells following vaginal implantation, and that vaginal repair was stimulated in the group of rats that received MDSC/SIS implants as compared to those who received SIS alone.

Continuing on their previous findings that active urethral closure during sneezing can be enhanced by noradrenergic pathways, Dr. Furuta and colleagues from Pittsburgh, PA and Tokyo, Japan set out to determine if a similar phenomenon occurred during passive intravesical pressure rises during Valsalva maneuver (Abstract #1372). In an elaborate rat study in which the adrenergic receptors of the smooth and striated musculature were manipulated, the group demonstrated findings that may be useful in facilitating further understanding of the nerve mediation of urethral closure during stress maneuvers.

Using urinary frequency as an indicator of overactive bladder (OAB), Dr. Gousse and colleagues from Miami, FL demonstrated that botulinum toxin A (BoNT-A) significantly decreases urinary frequency in patients deemed to have OAB (Abstract #1374). Furthermore, no difference in efficacy was noted between two groups of patients who received 100 and 150 units of BoNT-A.

An interesting epidemiological study from Philadelphia (Abstract #1375) used validated instruments to evaluate the prevalence of depression and physical, sexual, and emotional abuse amongst women with interstitial cystitis/painful bladder syndrome (IC/PBS). Based on their findings that IC/PBS patients have a significantly higher prevalence of depression and sexual abuse than the general population (albeit equivalent emotional and physical abuse), the authors recommended screening of IC/PBS patients for depression and consideration of referral of IC/PBS patients to a mental health expert as necessary.

Rats that have undergone vaginal distension have been used as an animal model to simulate the effects of vaginal delivery on the pelvic floor. The Cleveland Clinic group had previously demonstrated vaginal and urethral up-regulation of monocyte chemotactic protein-3 (MCP-3), a cytokine that signals stem cells to migrate to a site of injury. In an attempt to identify factors important in the process of tissue recovery, investigators sought to evaluate the effect of the duration of vaginal distension on cytokine and cytokine receptor expression (Abstract #1377), with specific attention paid to those cytokines involved in stem cell homing. Various factors, including MCP-3 and associated receptors, an ischemic marker, and inflammation-related IL8 were measured following vaginal distension of 0, 1, 4, 6 hours duration in a rat model. The findings suggested a strong relationship of the duration of vaginal distension with MCP-3, but a limited role of inflammation and ischemia on the recovery of the bladder and urethral tissues.

Dr. Christian Wallner and associates from the Netherlands (Abstract #1381), who received the best of session award for this forum, performed a detailed study of cadaveric pelves in two female fetuses, one male infant, and one male and two female adults. The fetal sections revealed a complete absence of smooth muscle actin (SMA) in contrast to the high expression of SMA seen in the male infant and all adult subjects. Based on these findings and previous work that had demonstrated differentiation of fibroblasts into smooth muscle in response to stretch stimuli, the group concluded that the smooth muscle seen in the infant and adult pelves likely represented myofibroblasts that had responded to the mechanical stresses of intra-abdominal pressure changes.

This group from Turkey examined the effect of estrogen and testosterone replacement on bladder contractility and histomorphology following ovariectomy (Abstract #1387). 54 rats were divided into six groups, all of which underwent ovariectomy except the control group. The remaining five groups received treatment with vehicle agent, estrogen alone, testosterone alone, estrogen and testosterone, or no supplementation for 6 weeks beginning 3 weeks post-ovariectomy. Ovariectomy is associated with detrusor atrophy, urothelial degeneration, and increased relaxation response, all of which were reversed by exogenous estrogen. Testosterone was associated with increased contractility, suggesting a possible role of both estrogen and testosterone in age-related bladder conditions.

ABST #1369: Skeletal Muscie-Derived Stem Cells (MDSC) Seeded on Small Intestinal Submucosal (SIS) Scaffolds Stimulate Vaginal Repair in the Rat, by Matthew H. Ho, MD, et al.

ABST #1372: Noradrenergic Mechanisms in the Urethral Continence Reflex Congrolling Urethral Smooth and Striated Muscle Function in Rats, by Akira Furuta, MD, et al.

ABST #1374: 100 vs. 150 Units of Intra-Detrusor Botox ®: Dose Differences in OAB-Dry Patients? by Angelo E. Grousse, MD, et al.

ABST #1375: A Cross-Sectional Investigation of the Prevalence of Depression and Abuse Among Women Diagnosed with Interstitial Cystitis/Painful Bladder Syndrome, by Pegah Safaeian, MD, el al.

ABST #1377: Cytokine Expression After Vaginal Distension of Different Durations in Virgin Strague Dawley Rats, by Hadley M. Wood, MD, et al.

ABST #1381: Age-Related Smooth Muscle Formation in Pelvic Connective Tissue, by Christian Wallner, MD, et al.

ABST #1387: Exogenous Testosterone and Estrogen Affect Bladder Tissue Contractility and Histomorphology Differently in a Rat Ovariectomy Model, by Yilloren Taniir, MD, et al.

Presented at the Annual Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.

Reported by UroToday.com Contributing Editor Kathleen C. Kobashi, MD

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