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Adipose-Derived Stem Cells Inhibit the Contractile Myofibroblast in Dupuytren's Disease

Verhoekx, Jennifer S. N. M.Sc.; Mudera, Vivek Ph.D.; Walbeehm, Erik T. M.D., Ph.D.; Hovius, Steven E. R. M.D., Ph.D.

doi: 10.1097/PRS.0b013e3182a3bf2b
Experimental: Original Articles

Background: In an attempt to provide minimally invasive treatment for Dupuytren's disease, percutaneous disruption of the affected tissue followed by lipografting is being tested. Contractile myofibroblasts drive this fibroproliferative disorder, whereas stem cells have recently been implicated in preventing fibrosis. Therefore, the authors tested the role of stem cells in modulating myofibroblast activity in Dupuytren's disease.

Methods: The authors compared the effect of co-culturing Dupuytren's myofibroblasts with either adipose-derived or bone-marrow–derived stem cells on isometric force contraction and associated levels of α-smooth muscle actin mRNA and protein expression. The authors also tested the effect of these stem cells on Dupuytren's myofibroblast proliferation and assessed whether this was mediated by cell-to-cell contact or by a paracrine mechanism.

Results: Addition of adipose-derived stem cells to Dupuytren's myofibroblasts reduced the contraction of the latter, with a corresponding reduction of α-smooth muscle actin protein expression, probably through a dilution effect. In contrast, bone marrow–derived stem cells increased myofibroblast contractility. In addition, adipose-derived stem cells inhibit myofibroblast proliferation and mediate these effects by soluble factors, influenced by cell-to-cell contact–dependent signaling.

Conclusion: Adipose-derived stem cells inhibit the contractile myofibroblast in Dupuytren's disease, and these findings lend support to the potential benefit of lipografting in conjunction with aponeurotomy as a novel strategy for the treatment of Dupuytren's disease.

Rotterdam, The Netherlands; and Stanmore, United Kingdom

From the Department of Plastic and Reconstructive Surgery, Erasmus Medical Center; and the Institute of Orthopedics and Musculoskeletal Sciences, University College London.

Received for publication February 27, 2013; accepted May 15, 2013.

Presented at the First Research Council Meeting of the European Association of Plastic Surgeon, in Munich, Germany, May 23 through 24, 2012; and the Winter Scientific Meeting of the British Association of Plastic, Reconstructive, and Aesthetic Surgeons, in London, United Kingdom, December 4 through 7, 2012.

Disclosure: The authors have no financial interest to declare in relation to the content of this article.

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Jennifer S. N. Verhoekx, M.Sc., Department of Plastic, Reconstructive, and Hand Surgery, Erasmus Medical Centre, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands, jsn.verhoekx@gmail.com

©2013American Society of Plastic Surgeons