Ruiz-Zapata Alejandra M, Kerkhof Manon H, Zandieh-Doulabi Behrouz, Brölmann Hans A M, Smit Theo H, Helder Marco N
Department of Orthopedic Surgery, VU University Medical Center, Research Institute MOVE, Amsterdam 1007MB, The Netherlands
Department of Obstetrics & Gynaecology, VU University Medical Center, Amsterdam 1007MB, The Netherlands.
Mol Hum Reprod. 2014 Nov;20(11):1135-43. doi: 10.1093/molehr/gau078. Epub 2014 Sep 4.
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.
盆腔器官脱垂（POP）仍然是一个巨大的治疗挑战，目前尚无最佳治疗方法。成纤维细胞负责组织维持和重塑，因此细胞功能改变可能会影响组织质量。在本研究中，我们评估了参与盆腔器官脱垂组织中纤维母细胞的功能特征。为排除正常衰老导致的组织退化，在8例健康和10例盆腔器官脱垂膀胱膨出患者（POP-Q分期≥II期）子宫切除术后，从绝经前18名女性的宫颈前区域（非盆腔器官脱垂部位）采集活检组织。在盆腔器官脱垂病例中，从脱垂部位获取额外组织，以区分内在和后天性细胞缺陷。对28种原代成纤维细胞培养物进行了体外研究。采用收缩性试验检测成纤维细胞介导的胶原收缩。通过在蛋白质或基因表达水平测量基质重塑因子，评估细胞在胶原包被或未包被基质上的机械反应。对照组和成组病例非盆腔器官脱垂部位的成纤维细胞之间未发现差异。脱垂部位的成纤维细胞在胶原包被板上显示出成纤维细胞介导的胶原收缩延迟，基质金属蛋白酶-2（MMP-2）产生降低。在未包被表面，盆腔器官脱垂部位成纤维细胞中MMP-2基因及其金属蛋白酶组织抑制剂-2上调。总之，与非脱垂部位相比，膀胱膨出患者脱垂组织来源的成纤维细胞根据表面基质显示出体外功能特征改变。这意味着大多数膀胱膨出患者存在后天性而非先天性缺陷，在尝试改善盆腔器官脱垂治疗时应予以考虑。
