title: Functional characteristics of vaginal fibroblastic cells from premenopausal women with pelvic organ prolapse.
abstract: Pelvic organ prolapse (POP) remains a great therapeutic challenge with no optimal treatment available. Tissue maintenance and remodelling are performed by fibroblasts, therefore altered cellular functionality may influence tissue quality. In this study, we evaluated functional characteristics of fibroblastic cells from tissues involved in POP. To rule out normal ageing tissue degeneration, biopsies from 18 premenopausal women were collected from the precervical region (non-POP site) after hysterectomy of 8 healthy and 10 POP cystocele cases (POP-Q stage ≥ II). Extra tissues from the prolapsed sites were taken in the POP cases to distinguish between intrinsic and acquired cellular defects. Twenty-eight primary fibroblastic 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 remodelling factors at protein or gene expression levels. No differences were found between fibroblasts from the controls and the non-POP site of the case group. Fibroblastic cells 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 tissue inhibitor of metalloproteinases-2 were up-regulated in POP site fibroblastic cells. In conclusion, fibroblastic cells derived from prolapsed tissues of patients with cystocele, display altered in vitro functional characteristics depending on the surface substrate and compared with non-prolapsed site. This implies an acquired rather than an intrinsic defect for most patients with cystocele, and should be taken into account when trying to improve treatments for POP.
authors.affiliation: Department of Orthopedic Surgery, VU University Medical Center, Research Institute MOVE, Amsterdam 1007MB, The Netherlands a.ruiz@acta.nl.
authors.forename: Alejandra M
authors.initials: AM
authors.lastname: Ruiz-Zapata
authors.affiliation: Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam 1007MB, The Netherlands.
authors.forename: Manon H
authors.initials: MH
authors.lastname: Kerkhof
authors.affiliation: Department of Oral Cell Biology, ACTA - University of Amsterdam and VU University, Research Institute MOVE, Amsterdam 1081LA, The Netherlands.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Zandieh-Doulabi
authors.affiliation: Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam 1007MB, The Netherlands.
authors.forename: Hans A M
authors.initials: HA
authors.lastname: Brölmann
authors.affiliation: Department of Orthopedic Surgery, VU University Medical Center, Research Institute MOVE, Amsterdam 1007MB, The Netherlands.
authors.forename: Theo H
authors.initials: TH
authors.lastname: Smit
authors.affiliation: Department of Orthopedic Surgery, VU University Medical Center, Research Institute MOVE, Amsterdam 1007MB, The Netherlands.
authors.forename: Marco N
authors.initials: MN
authors.lastname: Helder
mesh_terms: D000328:Adult; D001696:Biomechanical Phenomena; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2; D056887:Pelvic Organ Prolapse / Q000378:metabolism / Q000473:pathology*; D017697:Premenopause; D014621:Vagina / Q000378:metabolism / Q000473:pathology*
chemical_list: D003094:Collagen; D020778:Matrix Metalloproteinase 2
keywords: contractility assay; cyclic mechanical loading; matrix remodelling factors; pelvic organ prolapse; vaginal fibroblasts