Skip to main content
Top
Published in: International Urogynecology Journal 9/2013

Open Access 01-09-2013 | Original Article

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

Authors: Alejandra M. Ruiz-Zapata, Manon H. Kerkhof, Behrouz Zandieh-Doulabi, Hans A. M. Brölmann, Theo H. Smit, Marco N. Helder

Published in: International Urogynecology Journal | Issue 9/2013

Login to get access

Abstract

Introduction and hypothesis

Little 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.

Methods

Fibroblasts 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.

Results

POP fibroblasts show delayed cell alignment and lower responses to extracellular matrix remodelling factors at both enzymatic- and gene-expression levels compared with healthy fibroblasts.

Conclusion

POP 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.
Literature
2.
go back to reference Mosier E, Lin VK, Zimmern P (2010) Extracellular matrix expression of human prolapsed vaginal wall. Neurourol Urodyn 29:582–586PubMedCrossRef Mosier E, Lin VK, Zimmern P (2010) Extracellular matrix expression of human prolapsed vaginal wall. Neurourol Urodyn 29:582–586PubMedCrossRef
4.
go back to reference Keys T, Campeau L, Badlani G (2012) Synthetic mesh in the surgical repair of pelvic organ prolapse: current status and future directions. Urology 80:237–243PubMedCrossRef Keys T, Campeau L, Badlani G (2012) Synthetic mesh in the surgical repair of pelvic organ prolapse: current status and future directions. Urology 80:237–243PubMedCrossRef
5.
go back to reference Kerkhof MH, Hendriks L, Brölmann HAM (2009) Changes in connective tissue in patients with pelvic organ prolapse—a review of the current literature. Int Urogynecol J Pelvic Floor Dysfunct 20:461–474PubMedCrossRef Kerkhof MH, Hendriks L, Brölmann HAM (2009) Changes in connective tissue in patients with pelvic organ prolapse—a review of the current literature. Int Urogynecol J Pelvic Floor Dysfunct 20:461–474PubMedCrossRef
6.
go back to reference Feola A, Barone W, Moalli P, Abramowitch S (2012) Characterizing the ex vivo textile and structural properties of synthetic prolapse mesh products. Int Urogynecol J. doi:10.1007/s00192-012-1901-1 Feola A, Barone W, Moalli P, Abramowitch S (2012) Characterizing the ex vivo textile and structural properties of synthetic prolapse mesh products. Int Urogynecol J. doi:10.​1007/​s00192-012-1901-1
7.
go back to reference Moalli PA, Shand SH, Zyczynski HM, Gordy SC, Meyn LA (2005) Remodeling of vaginal connective tissue in patients with prolapse. Obstet Gynecol 106:953–963PubMedCrossRef Moalli PA, Shand SH, Zyczynski HM, Gordy SC, Meyn LA (2005) Remodeling of vaginal connective tissue in patients with prolapse. Obstet Gynecol 106:953–963PubMedCrossRef
8.
go back to reference Bortolini MA, Shynlova O, Drutz HP et al (2011) Expression of bone morphogenetic protein-1 in vaginal tissue of women with severe pelvic organ prolapse. Am J Obstet Gynecol 204:544.e1–8CrossRef Bortolini MA, Shynlova O, Drutz HP et al (2011) Expression of bone morphogenetic protein-1 in vaginal tissue of women with severe pelvic organ prolapse. Am J Obstet Gynecol 204:544.e1–8CrossRef
9.
go back to reference Jean-Charles C, Rubod C, Brieu M, Boukerrou M, Fasel J, Cosson M (2010) Biomechanical properties of prolapsed or non-prolapsed vaginal tissue: impact on genital prolapse surgery. Int Urogynecol J 21:1535–1538PubMedCrossRef Jean-Charles C, Rubod C, Brieu M, Boukerrou M, Fasel J, Cosson M (2010) Biomechanical properties of prolapsed or non-prolapsed vaginal tissue: impact on genital prolapse surgery. Int Urogynecol J 21:1535–1538PubMedCrossRef
10.
go back to reference Martins P, Silva-Filho AG, Maciel da Fonseca AMR, Santos A, Santos L, Mascarenhas T, Jorge RMN, Ferreira AJM (2012) Biomechanical properties of vaginal tissue in women with pelvic organ prolapse. Gynecol Obstet Invest. doi:10.1007/s00192-012-1901-1 Martins P, Silva-Filho AG, Maciel da Fonseca AMR, Santos A, Santos L, Mascarenhas T, Jorge RMN, Ferreira AJM (2012) Biomechanical properties of vaginal tissue in women with pelvic organ prolapse. Gynecol Obstet Invest. doi:10.​1007/​s00192-012-1901-1
11.
go back to reference Zhou L, Lee JH, Wen Y, Constantinou C, Yoshinobu M, Omata S, Chen B (2012) Biomechanical properties and associated collagen composition in vaginal tissue of women with pelvic organ prolapse. J Urol 188(3):875–880PubMedCrossRef Zhou L, Lee JH, Wen Y, Constantinou C, Yoshinobu M, Omata S, Chen B (2012) Biomechanical properties and associated collagen composition in vaginal tissue of women with pelvic organ prolapse. J Urol 188(3):875–880PubMedCrossRef
12.
go back to reference Phillips CH, Anthony F, Benyon C, Monga AK (2006) Collagen metabolism in the uterosacral ligaments and vaginal skin of women with uterine prolapse. BJOG 113:39–46PubMedCrossRef Phillips CH, Anthony F, Benyon C, Monga AK (2006) Collagen metabolism in the uterosacral ligaments and vaginal skin of women with uterine prolapse. BJOG 113:39–46PubMedCrossRef
13.
go back to reference Liang CC, Huang HY, Tseng LH, Chang SD, Lo TS, Lee CL (2010) Expression of matrix metalloproteinase-2 and tissue inhibitors of metalloproteinase-1 (TIMP-1, TIMP-2 and TIMP-3) in women with uterine prolapse but without urinary incontinence. Eur J Obstet Gynecol Reprod Biol 153:94–98PubMedCrossRef Liang CC, Huang HY, Tseng LH, Chang SD, Lo TS, Lee CL (2010) Expression of matrix metalloproteinase-2 and tissue inhibitors of metalloproteinase-1 (TIMP-1, TIMP-2 and TIMP-3) in women with uterine prolapse but without urinary incontinence. Eur J Obstet Gynecol Reprod Biol 153:94–98PubMedCrossRef
14.
go back to reference Berger MB, Ramanah R, Guire KE, Delancey JOL (2012) Is cervical elongation associated with pelvic organ prolapse? Int Urogynecol J 23:1095–1103PubMedCrossRef Berger MB, Ramanah R, Guire KE, Delancey JOL (2012) Is cervical elongation associated with pelvic organ prolapse? Int Urogynecol J 23:1095–1103PubMedCrossRef
15.
go back to reference Word RA, Pathi S, Schaffer JI (2009) Pathophysiology of pelvic organ prolapse. Obstet Gynecol Clin N Am 36:521–539CrossRef Word RA, Pathi S, Schaffer JI (2009) Pathophysiology of pelvic organ prolapse. Obstet Gynecol Clin N Am 36:521–539CrossRef
16.
go back to reference Jackson SR, Eckford SD, Abrams P, Avery NC, Tarlton JF, Bailey AJ (1996) Changes in metabolism of collagen in genitourinary prolapse. Lancet 347:1658–1661PubMedCrossRef Jackson SR, Eckford SD, Abrams P, Avery NC, Tarlton JF, Bailey AJ (1996) Changes in metabolism of collagen in genitourinary prolapse. Lancet 347:1658–1661PubMedCrossRef
17.
go back to reference Budatha M, Roshanravan S, Zheng Q et al (2011) Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans. J Clin Invest 121:2048–2059PubMedCrossRef Budatha M, Roshanravan S, Zheng Q et al (2011) Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans. J Clin Invest 121:2048–2059PubMedCrossRef
18.
go back to reference Blaauboer ME, Smit TH, Hanemaaijer R, Stoop R, Everts V (2011) Cyclic mechanical stretch reduces myofibroblast differentiation of primary lung fibroblasts. Biochem Biophys Res Commun 404:23–27PubMedCrossRef Blaauboer ME, Smit TH, Hanemaaijer R, Stoop R, Everts V (2011) Cyclic mechanical stretch reduces myofibroblast differentiation of primary lung fibroblasts. Biochem Biophys Res Commun 404:23–27PubMedCrossRef
19.
go back to reference Perez-Amodio S, Beertsen W, Everts V (2004) (Pre-)osteoclasts induce retraction of osteoblasts before their fusion to osteoclasts. J Bone Miner Res 19:1722–1731PubMedCrossRef Perez-Amodio S, Beertsen W, Everts V (2004) (Pre-)osteoclasts induce retraction of osteoblasts before their fusion to osteoclasts. J Bone Miner Res 19:1722–1731PubMedCrossRef
20.
go back to reference Kong D, Ji B, Dai L (2008) Stability of adhesion clusters and cell reorientation under lateral cyclic tension. Biophys J 95:4034–4044PubMedCrossRef Kong D, Ji B, Dai L (2008) Stability of adhesion clusters and cell reorientation under lateral cyclic tension. Biophys J 95:4034–4044PubMedCrossRef
21.
go back to reference Ewies AAA, Elshafie M, Li J et al (2008) Changes in transcription profile and cytoskeleton morphology in pelvic ligament fibroblasts in response to stretch: the effects of estradiol and levormeloxifene. Mol Hum Reprod 14:127–135PubMedCrossRef Ewies AAA, Elshafie M, Li J et al (2008) Changes in transcription profile and cytoskeleton morphology in pelvic ligament fibroblasts in response to stretch: the effects of estradiol and levormeloxifene. Mol Hum Reprod 14:127–135PubMedCrossRef
22.
go back to reference Zong W, Jallah ZC, Stein SE, Abramowitch SD, Moalli PA (2010) Repetitive mechanical stretch increases extracellular collagenase activity in vaginal fibroblasts. Female Pelvic Med Reconstr Surg 16:257–262PubMedCrossRef Zong W, Jallah ZC, Stein SE, Abramowitch SD, Moalli PA (2010) Repetitive mechanical stretch increases extracellular collagenase activity in vaginal fibroblasts. Female Pelvic Med Reconstr Surg 16:257–262PubMedCrossRef
23.
go back to reference Ozog Y, Kostantinovic M, Werbrouck E, De Ridder D, Mazza E, Deprest J (2011) Persistence of polypropylene mesh anisotropy after implantation: an experimental study. BJOG 118:1180–1185PubMedCrossRef Ozog Y, Kostantinovic M, Werbrouck E, De Ridder D, Mazza E, Deprest J (2011) Persistence of polypropylene mesh anisotropy after implantation: an experimental study. BJOG 118:1180–1185PubMedCrossRef
24.
go back to reference Feola A, Abramowitch S, Jallah Z, Stein S, Barone W, Palcsey S, Moally P (2013) Deterioration in biomechanical properties of the vagina following implantation of high-stiffness prolapse mesh. BJOG 120:224–232PubMedCrossRef Feola A, Abramowitch S, Jallah Z, Stein S, Barone W, Palcsey S, Moally P (2013) Deterioration in biomechanical properties of the vagina following implantation of high-stiffness prolapse mesh. BJOG 120:224–232PubMedCrossRef
Metadata
Title
Fibroblasts from women with pelvic organ prolapse show differential mechanoresponses depending on surface substrates
Authors
Alejandra M. Ruiz-Zapata
Manon H. Kerkhof
Behrouz Zandieh-Doulabi
Hans A. M. Brölmann
Theo H. Smit
Marco N. Helder
Publication date
01-09-2013
Publisher
Springer London
Published in
International Urogynecology Journal / Issue 9/2013
Print ISSN: 0937-3462
Electronic ISSN: 1433-3023
DOI
https://doi.org/10.1007/s00192-013-2069-z

Other articles of this Issue 9/2013

International Urogynecology Journal 9/2013 Go to the issue