Iqbal Syed Amir, Hayton Michael John, Watson James Stewart, Szczypa Piotr, Bayat Ardeshir
Plastic & Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom.
Department of Hand and Upper Limb Surgery, Wrightington Hospital, Wrightington, United Kingdom.
PLoS One. 2014 Jun 16;9(6):e99967. doi: 10.1371/journal.pone.0099967. eCollection 2014.
Dupuytren's disease (DD) is a common progressive fibroproliferative disorder causing permanent digital contracture. Proliferative myofibroblasts are thought to be the cells responsible for DD initiation and recurrence, although their source remains unknown. DD tissue has also been shown to harbor mesenchymal and hematopoietic stem cells. Fibrocytes are circulating cells that show characteristics of fibroblasts and they express surface markers for both hematopoietic and mesenchymal stromal cells. Fibrocytes differentiate from peripheral CD14+ mononuclear cells, which can be inhibited by serum amyloid P (SAP). In this study we have demonstrated the presence of fibrocytes in DD blood and tissue, moreover we have evaluated the effects of SAP and Xiapex (Collagenase Clostridium histolyticum) on fibrocytes derived from DD. H&E staining showed typical Spindle shaped morphology of fibrocytes. FACS analysis based on a unique combination of 3 markers, revealed the increased presence of fibrocytes in blood and tissue of DD patients. Additionally, immunohistology of DD nodule and cord tissue showed the presence of collagen 1+/CD34+ cells. No difference in plasma SAP levels was observed between DD and control. Higher concentrations of SAP significantly inhibited fibrocytes differentiated from DD derived monocytes compared to control. DD fascia derived fibrocytes showed resistance to growth inhibition by SAP, particularly nodule derived fibrocytes showed robust growth even at higher SAP concentrations compared to control. DD derived fibrocytes were positive for typical fibrocyte dual markers, i.e. Collagen 1/LSP-1 and collagen 1/CD34. Xiapex was more effective in inhibiting the growth of nodule derived cells compared to commercially available collagenase A. Our results show for the first time the increased presence of fibrocytes in DD patient's blood and disease tissue compared to control tissue. Additionally, we evaluate the response of these fibrocytes to SAP and Xiapex therapy.
掌腱膜挛缩症（DD）是一种常见的进行性纤维增生性疾病，可导致永久性手指挛缩。增殖性肌成纤维细胞被认为是引发和复发DD的细胞，尽管其来源尚不清楚。DD组织也已被证明含有间充质和造血干细胞。纤维细胞是循环细胞，具有成纤维细胞的特征，并且表达造血和间充质基质细胞的表面标志物。纤维细胞由外周CD14 +单核细胞分化而来，而血清淀粉样蛋白P（SAP）可抑制这种分化。在本研究中，我们证实了DD血液和组织中存在纤维细胞，此外，我们评估了SAP和喜疗妥（溶组织梭状芽孢杆菌胶原酶）对源自DD的纤维细胞的影响。苏木精-伊红染色显示纤维细胞具有典型的纺锤形形态。基于三种标志物独特组合的流式细胞术分析显示，DD患者血液和组织中纤维细胞的数量增加。此外，DD结节和条索组织的免疫组织学检查显示存在Ⅰ型胶原+/CD34 +细胞。DD患者与对照组之间的血浆SAP水平无差异。与对照组相比，较高浓度的SAP显著抑制了源自DD单核细胞分化的纤维细胞。DD筋膜来源的纤维细胞对SAP的生长抑制具有抗性，特别是结节来源的纤维细胞，即使在较高SAP浓度下与对照组相比仍显示出强劲的生长。DD来源的纤维细胞对典型的纤维细胞双重标志物呈阳性，即Ⅰ型胶原/LSP-1和Ⅰ型胶原/CD34。与市售的胶原酶A相比，喜疗妥在抑制结节来源细胞的生长方面更有效。我们的结果首次表明，与对照组织相比，DD患者血液和疾病组织中纤维细胞的数量增加。此外，我们评估了这些纤维细胞对SAP和喜疗妥治疗的反应。
