Adipose-derived stem cells inhibit the contractile myofibroblast in Dupuytren's disease.

Abstract

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 alpha-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 alpha-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.