The Presence of Myofibroblasts in the Dermis of Patients with Dupuytren’s Contracture

McCann, B.; Logan, A. M.; Belcher, H.J.C.R.; Warn, A.; Warn, R. M.

doi:10.1016/0266-7681(93)90029-f

Cited by 38 publications

(21 citation statements)

References 7 publications

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“…The main cell type responsible for DD is thought to be the myofibroblasts that are derived from the resident fibroblasts in normal fascia [8,9]. In DD, skin overlying nodular (SON) tissue as well as perinodular fat (PNF) have been shown to be abnormal and it has been suggested that they may have a role in the pathogenesis of DD [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Identification of Mesenchymal Stem Cells in Perinodular Fat and Skin in Dupuytren's Disease: A Potential Source of Myofibroblasts with Implications for Pathogenesis and Therapy

Iqbal

Manning

Syed

et al. 2012

Stem Cells and Development

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Dupuytren's disease (DD) is a fibroproliferative disorder characterized by aberrant proliferation of myofibroblasts, the source of which remains unknown. Recent studies indicate that circulating and tissue-resident mesenchymal stem cells (MSCs) can differentiate into myofibroblasts. Therefore, the aim of this study was to profile MSCs from phenotypically distinct DD sites including cord, nodule, skin overlying nodule (SON), and perinodular fat (PNF) compared with unaffected internal controls, that is, distant palmar fat (DPF) and transverse palmar fascia (Skoog's fibers) as well as external control carpal tunnel (CT) tissue including skin, fat, and fascia. Freshly isolated primary fibroblasts as well as cells grown up to passage 5 (P5) from DD (n=27) and CT (n=14) samples were analyzed for the presence of established MSC markers CD73, CD90, and CD105 and absence of hematopoietic marker CD34 using fluorescence-activated cell sorting, in-cell quantitative western blotting, immunohistochemistry, and immunocytochemistry. Freshly isolated cells from SON, PNF, and cord biopsies had a higher number of CD34(-)73(+)90(+)105(+) cells compared with Skoog's fibers and CT controls. P3 cells obtained from all DD biopsies compared with CT samples differentiated into osteocytes, adipocytes, and chondrocytes. P3 cord and nodule cells expressed intense α-smooth muscle actin staining compared with skin and fat cells. Stem cell markers including stem cell factor, MSC-homing marker CXCR4, and Wnt/β-catenin downregulator Dkk-1 were all upregulated in SON and PNF compared with CT skin and CT fat, respectively, as shown by real-time quantitative polymerase chain reaction. However, osteogenic marker OSF-1 had a significantly higher expression in the PNF (P=0.002) and cord (P=0.01) compared with the nodule. In conclusion, we have shown the presence of MSCs in specific DD tissue phenotypes compared with internal and external control tissue. These findings provide preliminary support for a potential alternative source of disease myofibroblasts originating from sites such as SON and PNF as opposed to palmar fascia alone.

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Section: Introductionmentioning

confidence: 99%

Identification of Mesenchymal Stem Cells in Perinodular Fat and Skin in Dupuytren's Disease: A Potential Source of Myofibroblasts with Implications for Pathogenesis and Therapy

Iqbal

Manning

Syed

et al. 2012

Stem Cells and Development

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“…Significantly, equations (6)- (8) imply that if c > 0 and n > 0, then m f 0, so that any pathological state with a persistent inflammatory component (indicated by c > 0) exhibits a permanent myofibroblastic profile, which is a paradigm of an important class of fibro-proliferative pathologies (Ehrlich et al, 1994;McCann et al, 1993;Murray, 1993;Rudolph and Vande Berg, 1991;Schiirch et al, 1990;Skalli and Gabbiani, 1988).…”

Section: Pathological Steady Statesmentioning

confidence: 99%

“…Second, what mechanisms might cause a fibro-proliferative disorder to partially or fully regress? The clinical occurrence, extent and permanence of regression is unpredictable and unexplained (McCann et al, 1993;Murray and Pinnell, 1992). These issues are addressed below.…”

Section: If K E Andmentioning

confidence: 99%

A mathematical model for fibro-proliferative wound healing disorders

Olsen¹,

Sherratt

Maini³

1996

Bltn Mathcal Biology

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The normal process of dermal wound healing fails in some cases, due to fibro-proliferative disorders such as keloid and hypertrophic scars. These types of abnormal healing may be regarded as pathologically excessive responses to wounding in terms of fibroblastic cell profiles and their inflammatory growth-factor mediators. Biologically, these conditions are poorly understood and current medical treatments are thus unreliable.In this paper, the authors apply an existing deterministic mathematical model for fibroplasia and wound contraction in adult mammalian dermis (Olsen et al., J. theor. Biol. 177, 113-128, 1995) to investigate key clinical problems concerning these healing disorders. A caricature model is proposed which retains the fundamental cellular and chemical components of the full model, in order to analyse the spatiotemporal dynamics of the initiation, progression, cessation and regression of fibro-contractive diseases in relation to normal healing. This model accounts for fibroblastic cell migration, proliferation and death and growth-factor diffusion, production by cells and tissue removal/decay.Explicit results are obtained in terms of the model processes and parameters. The rate of cellular production of the chemical is shown to be critical to the development of a stable pathological state. Further, cessation and/or regression of the disease depend on appropriate spatiotemporally varying forms for this production rate, which can be understood in terms of the bistability of the normal dermal and pathological steady states-a central property of the model, which is evident from stability and bifurcation analyses.The work predicts novel, biologically realistic and testable pathogenic and control mechanisms, the understanding of which will lead toward more effective strategies for clinical therapy of fibro-proliferative disorders.

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“…Dermal fibromatosis has been 21 demonstrated within the palmar skin of patients with both primary and recurrent Dupuytren's 22 disease [1][2][3] . Also, dermofasciectomy with full thickness skin graft (FTSG) reconstruction appears to 23 alter the course of recurrence 2,4 .…”

Section: Introduction 18 19mentioning

confidence: 99%

“…The benefit of skin excision was explained by Logan and colleagues 74 when they showed Dupuytren's fibromatosis within the dermis and epidermis of patients with 75 recurrent disease, resulting in their conclusion that the only way to adequately treat disease of this 76 magnitude was by radical excision 1,7 . Recently, our group has also shown that Dupuytren's 77 fibromatosis also exists in the skin of patients without clinically apparent skin involvement 3 .…”

mentioning

confidence: 99%