Functional characteristics of vaginal fibroblasts from premenopausal women with pelvic organ prolapse

Objective: Pelvic organ prolapse (POP) remains a great therapeutic challenge with no optimal treatment available. Tissue maintenance and remodeling are performed by fibroblasts, therefore altered cellular functionality may influence tissue quality. In this study, we evaluated functional characteristics of fibroblasts from tissues involved in POP. Study design: To rule out normal ageing tissue degeneration biopsies from 18 premenopausal women were collected from the precervical region (non-POP site) after hysterectomy of eight healthy and 10 POP cystocele cases (POP-Q stage ≥ II). Extra tissues from the prolapsed site were taken in the POP cases to identify between intrinsic and acquired cellular defects. 28 primary fibroblast cultures were studied in vitro. A contractility assay was used to test fibroblast-mediated collagen contraction. Cellular mechanoresponses on collagen-coated or uncoated substrates were evaluated by measuring matrix remodeling factors at protein or gene expression levels. Results: No differences were found between fibroblasts from the controls and the non-POP site of the case group. Fibroblasts from the prolapsed site showed delayed fibroblast-mediated collagen contraction and lower production of matrix metalloproteinase-2 (MMP-2) on collagen-coated plates. On uncoated surfaces the gene MMP-2 and its inhibitor (TIMP-2) were up-regulated in POP site fibroblasts. Conclusion: Fibroblasts derived from prolapsed tissues of patients with cystocele, display altered in vitro functional characteristics depending on the matrix substrate and compared to non-prolapsed site. This implies an acquired rather than an intrinsic defect and should be taken into account when improving treatments for pelvic organ prolapse.