title: Vaginal Fibroblastic Cells from Women with Pelvic Organ Prolapse Produce Matrices with Increased Stiffness and Collagen Content.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, VU University medical center, Research Institute MOVE, Netherlands Institute for Regenerative Medicine, Amsterdam, The Netherlands.
authors.forename: Alejandra M
authors.initials: AM
authors.lastname: Ruiz-Zapata
authors.affiliation: Department of Orthopedic Surgery, VU University medical center, Research Institute MOVE, Netherlands Institute for Regenerative Medicine, Amsterdam, The Netherlands.
authors.forename: Manon H
authors.initials: MH
authors.lastname: Kerkhof
authors.affiliation: Department of Orthopedic Surgery, VU University medical center, Research Institute MOVE, Netherlands Institute for Regenerative Medicine, Amsterdam, The Netherlands.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Ghazanfari
authors.affiliation: Department of Oral Cell Biology, ACTA- University of Amsterdam and VU University, Research Institute MOVE, Amsterdam, The Netherlands.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Zandieh-Doulabi
authors.affiliation: TNO Metabolic Health Research, Leiden, The Netherlands.
authors.forename: Reinout
authors.initials: R
authors.lastname: Stoop
authors.affiliation: Department of Orthopedic Surgery, VU University medical center, Research Institute MOVE, Netherlands Institute for Regenerative Medicine, Amsterdam, 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, Netherlands Institute for Regenerative Medicine, Amsterdam, The Netherlands.
authors.forename: Marco N
authors.initials: MN
authors.lastname: Helder
mesh_terms: D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D017773:Pelvic Floor / Q000473:pathology*; D056887:Pelvic Organ Prolapse / Q000473:pathology*; D017698:Postmenopause / Q000378:metabolism / Q000502:physiology; D014621:Vagina / Q000378:metabolism / Q000473:pathology*
chemical_list: D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9