Manon H. Kerkhof

Fibroblasts from women with pelvic organ prolapse show differential mechanoresponses depending on surface substrates

Introduction and hypothesisLittle is known about dynamic cell-matrix interactions in the context of pathophysiology and treatments for pelvic organ prolapse (POP). This study sought to identify differences between fibroblasts from women with varying degrees of prolapse in reaction to mechanical stimuli and matrix substrates in vitro.MethodsFibroblasts from the vaginal wall of three patients with POP Quantification (POP-Q) system stages 0, II, and IV were stretched on artificial polymer substrates either coated or not coated with collagen I. Changes in morphology and anabolic/catabolic compounds that affect matrix remodelling were evaluated at protein- and gene-expression levels. Statistical analysis was performed using one-way analysis of variance (ANOVA), followed by Tukey-Kramer’s post hoc test.ResultsPOP fibroblasts show delayed cell alignment and lower responses to extracellular matrix remodelling factors at both enzymatic- and gene-expression levels compared with healthy fibroblasts.ConclusionPOP fibroblasts, when compared with healthy cells, show differential mechanoresponses on two artificial polymer substrates. This should be taken into account when designing or improving implants for treating POP.

Changes in tissue composition of the vaginal wall of premenopausal women with prolapse

OBJECTIVE The objective of this study was to compare histological and biochemical features of the (normal) precervical anterior vaginal wall and the prolapsed anterior vaginal wall of women with pelvic organ prolapse (POP). These data were compared to tissue of the precervical anterior vaginal wall of age-matched controls without POP to identify possible intrinsic and acquired effects. STUDY DESIGN Biopsies were collected from the apex of the anterior vaginal cuff after hysterectomy from a control group of 13 premenopausal women undergoing hysterectomy for benign gynecological diseases, and a case group of 13 premenopausal women undergoing prolapse surgery (cystocele POP-Quantification stage ≥2). In women with POP an additional full-thickness vaginal wall sample was taken from the POP site during anterior colporrhaphy. Histomorphometric and biochemical analysis were performed for different components of the extracellular matrix. RESULTS There were no differences between case and control group in the precervical vaginal wall tissue with respect to the different components of the extracellular matrix and the biochemical parameters. However, there was a tendency toward a higher amount of collagen III and elastin, and a significant increase of smooth muscle cells and pyridinoline collagen cross-links in the POP site compared to the non-POP site of the same POP patient. CONCLUSION Our findings suggest that the changes seen in connective tissue in the anterior vaginal wall of women with POP are the effect, rather than the cause, of POP.

Vaginal Fibroblastic Cells from Women with Pelvic Organ Prolapse Produce Matrices with Increased Stiffness and Collagen Content

Pelvic organ prolapse (POP) is characterised by the weakening of the pelvic floor support tissues, and often by subsequent prolapse of the bladder outside the body, i.e. cystocele. The bladder is kept in place by the anterior vaginal wall which consists of a dense extracellular matrix rich in collagen content that is maintained and remodelled by fibroblastic cells, i.e. fibroblasts and myofibroblasts. Since altered matrix production influences tissue quality, and myofibroblasts are involved in normal and pathological soft tissue repair processes, we evaluated matrix production of cells derived from pre- and post-menopausal POP and non-POP control anterior vaginal wall tissues. Results showed that cells from postmenopausal POP women deposited matrices with high percentage of collagen fibres with less anisotropic orientation and increased stiffness than those produced by controls. There was a transient increase in myofibroblastic phenotype that was lost after the peak of tissue remodelling. In conclusion, affected fibroblasts from postmenopausal prolapsed tissues produced altered matrices in vitro compared to controls. Such aberrant altered matrix production does not appear to be a consequence of abnormal phenotypical changes towards the myofibroblastic lineage.

Management of post-midurethral sling voiding dysfunction. International Urogynecological Association research and development committee opinion

Voiding dysfunction following midurethral sling procedures is not a rare event. There is no current consensus regarding management of this complication. Although it is often transient and self-limiting, chronic post-midurethral sling voiding dysfunction may lead to irreversible changes affecting detrusor function. Initial management includes intermittent catheterization, and addressing circumstantial factors interfering with normal voiding, such as pain. Early sling mobilization often resolves the dysfunction, and is associated with minimal morbidity. Sling incision or excision at a later stage, although fairly effective, could be associated with recurrence of stress urinary incontinence. There is insufficient evidence to justify urethral dilatation in this context.

Regenerative medicine as a therapeutic option for fecal incontinence: a systematic review of preclinical and clinical studies

Background: Fecal incontinence is the uncontrollable loss of stool and has a prevalence of around 7–15%. This condition has serious implications for patients’ quality of life. Current treatment options show unsatisfactory results. A novel treatment option is therefore needed. Objective: This systematic review aims to perform a quality assessment and to give a critical overview of the current research available on regenerative medicine as a treatment for fecal incontinence. Study Design: A systematic search strategy was applied in PubMed, Cochrane Library, EMBASE, MEDLINE, Web of Science, and Cinahl from inception until March of 2018. Studies were found relevant when the animals or patients in the studied group had objectively determined or induced fecal incontinence, and the intervention must have used any kind of cells, stem cells, or biocompatible material, with or without the use of trophic factors. Studies were screened on title and consecutively on abstract for relevance by 2 independent investigators. The risk of bias of preclinical studies was assessed using the SYstematic Review Centre for Laboratory animal Experimentation risk of bias tool for animal studies, and for clinical studies the Cochrane risk of bias tool for randomized trials was used. Results: In all, 34 preclinical studies and 5 clinical studies were included. Animal species, type of anal sphincter injury, intervention, and outcome parameters were heterogenous. Therefore, a meta‐analysis could not be performed. The overall risk of bias of the included studies was high. Conclusion: The efficacy of regenerative medicine to treat fecal incontinence could not be determined due to the high risk of bias and heterogenicity of the available preclinical and clinical studies. The findings of this systematic review may result in improved study design of future studies, which could help the translation of regenerative medicine to the clinic as an alternative to current treatments for fecal incontinence.