Bruna M. Couri

Stem Cell Therapy for Incontinence: Where Are We Now? What is the Realistic Potential?

A significant number of women experience stress urinary incontinence (SUI), which greatly affects their quality of life. Recent research investigating utilization of stem cells and their derivatives for the prevention and treatment of SUI has been performed to test the effect of cell source and method of administration in several animal models of SUI. The type of stem cell, timing of optimal dose or doses after injury, mechanism of action of stem cells, and route of administration must be investigated both preclinically and clinically before stem cell therapy becomes a possible treatment for SUI, although the future of this therapy looks promising. This article reviews the progress in stem cell research for incontinence and describes areas of future work as suggested by research in other fields.

Functional Status in Older Women Diagnosed with Pelvic Organ Prolapse

BACKGROUND Functional status plays an important role in the comprehensive characterization of older adults. Functional limitations are associated with an increased risk of adverse treatment outcomes, but there are limited data on the prevalence of functional limitations in older women with pelvic floor disorders. OBJECTIVE The aim of the study was to describe the prevalence of functional limitations based on health status in older women with pelvic organ prolapse (POP). STUDY DESIGN This pooled, cross-sectional study utilized data from the linked Health and Retirement Study and Medicare files from 1992 through 2008. The analysis included 890 women age ≥65 years with POP. We assessed self-reported functional status, categorized in strength, upper and lower body mobility, activities of daily living (ADL), and instrumental ADL (IADL) domains. Functional limitations were evaluated and stratified by respondents self-reported general health status. Descriptive statistics were used to compare categorical and continuous variables, and logistic regression was used to measure differences in the odds of functional limitation by increasing age. RESULTS The prevalence of functional limitations was 76.2% in strength, 44.9% in upper and 65.8% in lower body mobility, 4.5% in ADL, and 13.6% in IADL. Limitations were more prevalent in women with poor or fair health status than in women with good health status, including 91.5% vs 69.9% in strength, 72.9% vs 33.5% in upper and 88.0% vs 56.8% in lower body mobility, 11.6% vs 0.9% in ADL, and 30.6% vs 6.7% in IADL; all P < .01. The odds of all functional limitations also increased significantly with advancing age. CONCLUSION Functional limitations, especially in strength and body mobility domains, are highly prevalent in older women with POP, particularly in those with poor or fair self-reported health status. Future research is necessary to evaluate if functional status affects clinical outcomes in pelvic reconstructive and gynecologic surgery and whether it should be routinely assessed in clinical decision-making when treating older women with POP.

Validation of genetically matched wild-type strain and lysyl oxidase-like 1 knockout mouse model of pelvic organ prolapse.

Objectives Lysyl oxidase–like 1 knockout (Loxl1−/−) mice demonstrate deficient elastin homeostasis associated with pelvic organ prolapse (POP). To further investigate the pathophysiology of POP in these animals, a genetically matched homozygous positive (Loxl1+/+) or wild-type strain is needed. This study sought to create and validate genetically matched Loxl1+/+ and Loxl1−/− strains. Methods Female Loxl1−/− mice were backcrossed with male wild-type mice. The resultant heterozygous mice were bred to produce Loxl1+/+ and Loxl1−/− mice, whose genotype was confirmed by polymerase chain reaction (PCR). Multiparous female Loxl1−/− (n = 7) and Loxl1+/+ (n = 9) mice were assessed for POP weekly for 12 weeks after their first vaginal delivery. Pelvic organ prolapse was compared between groups using a Kaplan-Meier survival curve with P of less than 0.05 indicating a significant difference. Vaginal connective tissue histologic finding was assessed qualitatively and quantitatively. Results There were no significant differences between the groups in age or parity. Of the 7 Loxl1−/− mice, 4 developed prolapse by 8 weeks and 6 by 12 weeks postpartum. No Loxl1+/+ mouse prolapsed. Loxl1−/− mice had significantly larger vaginas as determined by area within the lumen and total cross-sectional tissue area. Striated muscle fibers of the urethra in Loxl1−/− mice were less organized, shorter, and thinner than in Loxl1+/+ mice. Conclusions Genetically matched Loxl1−/− and Loxl1+/+ strains can be reliably created by a backcross method and differentiate in their prolapse phenotype. Loxl1−/− mice demonstrate pathology primarily characterized by enlargement of the vagina. Further studies are needed to elucidate the cause of this finding.

Performance analysis of the T-DOC® air-charged catheters: An alternate technology for urodynamics

Urodynamics (UDS) is widely used for the diagnosis of lower urinary tract dysfunction. Air‐Charged catheters (ACC), one of the newer technologies for UDS pressure recording, has been adopted in growing numbers around the world for the past 15 years. Currently, there is a lack of published studies characterizing specific performance of the ACC. Since linearity, hysteresis, pressure drift, and frequency response are important components in characterizing accuracy for catheter‐manometer systems; this study aimed to assess these four aspects in ACC.

Induced Regenerative Elastic Matrix Repair in LOXL1 Knockout Mouse Cell Cultures: Towards Potential Therapy for Pelvic Organ Prolapse

Impaired elastic matrix remodeling occurs in reproductive tissues after vaginal delivery. This has been linked to development of pelvic organ prolapse (POP) for which there currently is no pharmacologic therapy. Hyaluronan oligomers and transforming growth factor beta 1 (termed elastogenic factors, EFs) have been shown to significantly enhance tropoelastin synthesis, elastic fiber assembly, and crosslinking by adult vascular smooth muscle cells (SMCs). The goal of this study was to ascertain if these factors similarly improve the quantity and quality of elastic matrix deposition by vaginal SMCs (VSMCs) isolated from lysyl oxidase like-1 knock out (LOXL1 KO) mouse model of POP. Cells isolated from whole vagina of a LOXL1 KO mouse (multiparous, stage 3 prolapse) were cultured and identified as SMCs by their expression of various SMC markers. Passage 2 vaginal SMCs (VSMCs; 3×104/10 cm2) were cultured for 21 days with EFs. Cell layers and spent medium aliquots were assessed for elastin content and quality. EF-treated VSMCs proliferated at a similar rate to untreated controls but synthesized more total elastin primarily in the form of soluble matrix elastin. Elastin mRNA was also increased compared to controls. The elastic matrix was significantly denser in EF-treated cultures, which was composed of more mature, non-interrupted elastic fibers that were absent in controls. The results are promising towards development of a therapy to enhance regenerative elastic matrix repair in post-partum female pelvic floor tissues.

Effect of Pregnancy and Delivery on Cytokine Expression in a Mouse Model of Pelvic Organ Prolapse

Objectives The aim of this study was to determine the effect of pregnancy and delivery mode on cytokine expression in the pelvic organs and serum of lysyl oxidase like-1 knockout (LOXL1 KO) mice, which develop pelvic organ prolapse after delivery. Methods Bladder, urethra, vagina, rectum, and blood were harvested from female LOXL1 KO mice during pregnancy, after vaginal or cesarean delivery, and from sham cesarean and unmanipulated controls. Pelvic organs and blood were also harvested from pregnant and vaginally delivered wild-type (WT) mice and from unmanipulated female virgin WT controls. Specimens were assessed using quantitative real-time reverse transcription polymerase chain reaction and/or enzyme-linked immunosorbent assay. Results Both CXCL12 and CCL7 mRNA were significantly up-regulated in the vagina, urethra, bladder, and rectum of pregnant LOXL1 KO mice compared with pregnant WT mice, suggesting systemic dysregulation of both of these cytokines in LOXL1 KO mice as a response to pregnancy. The differences in cytokine expression between LOXL1 KO and WT mice in pregnancy persisted after vaginal delivery. CCL7 gene expression increases faster and to a greater extent in LOXL1 KO mice, translating to longer lasting increases in CCL7 in serum of LOXL1 KO mice after vaginal delivery, compared with pregnant mice. Conclusions Lysyl oxidase like-1 KO mice have an increased cytokine response to pregnancy perhaps because they are less able to reform and re–cross-link stretched elastin to accommodate pups, and this resultant tissue stretches during pregnancy. The up-regulation of CCL7 after delivery could provide an indicator of level of childbirth injury, to which the urethra and vagina seem to be particularly vulnerable.

What was hot at the ICS meeting 2015: What Was Hot at the ICS Meeting 2015

Alison J. Hainsworth,* Paula Igualada-Martinez, Marianne Koch, Martha Spencer, Martin Slovak, Saladin Alloussi, Christopher Hillary, Bruna M. Couri, Nadir I. Osman, Rufus Cartwright, and Christopher R. Chapple Department of Colorectal, Pelvic Floor Unit, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom Department of Physiotherapy and Pelvic Floor Unit, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria Division of Geriatric Medicine, University of British Columbia, Vancouver, Canada Department of Medical Physics and Clinical Engineering, Sheffield Teaching Hospitals, Royal Hallamshire Hospital, Sheffield, United Kingdom NIHR Devices for Dignity Healthcare Technology Co-operative, Royal Hallamshire Hospitals, Sheffield, United Kingdom Department of Urology, Academic Teaching Hospital of University of Saarland, Stadtisches Klinikum Neunkirchen, Neunkirchen, Germany Department of Urology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom Department of Obstetrics and Gynaecology, Cleveland Clinic Lerner Research Institute, Cleveland Clinic, Cleveland Ohio Cleveland, Ohio Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland Clinic, Cleveland Ohio Cleveland, Ohio Department of Urogynaecology, Imperial College London, London, United Kingdom Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom