title: First identification of resident and circulating fibrocytes in Dupuytren's disease shown to be inhibited by serum amyloid P and Xiapex.
abstract: 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.
authors.affiliation: Plastic & Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom.
authors.forename: Syed Amir
authors.initials: SA
authors.lastname: Iqbal
authors.affiliation: Department of Hand and Upper Limb Surgery, Wrightington Hospital, Wrightington, United Kingdom.
authors.forename: Michael John
authors.initials: MJ
authors.lastname: Hayton
authors.affiliation: Department of Plastic and Reconstructive Surgery, University Hospital South Manchester NHS Foundation Trust, Wythenshawe Hospital, Manchester, United Kingdom.
authors.forename: James Stewart
authors.initials: JS
authors.lastname: Watson
authors.affiliation: Medical Affairs Pfizer Ltd, Tadworth, Surrey, United Kingdom.
authors.forename: Piotr
authors.initials: P
authors.lastname: Szczypa
authors.affiliation: Plastic & Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom; Department of Plastic and Reconstructive Surgery, University Hospital South Manchester NHS Foundation Trust, Wythenshawe Hospital, Manchester, United Kingdom.
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Bayat
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002349:Carpal Tunnel Syndrome / Q000097:blood; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D017364:Collagenases / Q000494:pharmacology*; D003710:Demography; D004387:Dupuytren Contracture / Q000097:blood*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008875:Middle Aged; D000683:Serum Amyloid P-Component / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D000683:Serum Amyloid P-Component; D017364:Collagenases; C570746:xiapex