Transforming Myofibroblasts Into Lipid-Filled Cells to Treat Dupuytren Disease

Purpose: Transforming myofibroblasts (MFs) into adipocyte-like cells may be a viable option for treating Dupuytren disease. Human Dupuytren MFs (DMFs) and adipose-derived stem cells (ASCs) cocultured in the presence of platelet-rich plasma (PRP) reprogrammed into lipid-laden cells. This treatment also reduced fibrosis markers in vivo. We aimed to determine whether this treatment transformed DMFs into adipocyte-like cells in vivo and characterize the PRP factors contributing to this transformation. Methods: Dupuytren MFs and normal human dermal fibroblasts were transplanted into the forepaws of rats (Rowett Nude [rnu/rnu]). Two months later, the paws were treated with saline, ASCs + PRP, or Clostridium histolyticum (clinical comparison) once a week for three treatments. The paw tissue was harvested 1 week after each treatment and subjected to Masson trichrome staining, collagen I and III, α-smooth muscle actin (SMA), and perilipin detection by immunohistochemistry. Dupuytren MFs were cocultured with ASCs and PRP or insulin-like growth factor I (IGF-I) or IGF-I-depleted PRP. In addition, the IGF-I receptor was inhibited. Oil Red O or boron-dipyrromethene detected lipid-laden cells. Results: Rodent paws implanted with DMFs showed enhanced α-SMA expression, imbalanced collagen III:I ratio, and reduced adipocytes compared with normal human dermal fibroblasts. After treatment with ASCs + PRP, DMF paws demonstrated reduced α-SMA, a balanced collagen III:I ratio, and a replenishment of adipocytes. Dupuytren MFs treated with ASCs + IGF-I transformed into adipocyte-like cells in vitro, which was validated by IGF-I-depletion and IGF-I receptor inhibition. Conclusions: Adipose-derived stem cells + PRP reduce fibrosis markers and induce adipocyte renewal in vivo. As a PRP component, IGF-I works with ASCs to transform DMFs into adipocyte-like cells in vitro. Clinical relevance: Identifying an active factor in PRP that synergizes with ASCs to transform DMFs into adipocyte-like cells may contribute to finding a novel therapeutic for Dupuytren disease. Such a treatment may allow for less-extensive surgical intervention coupled with therapeutic injection to reduce the recurrence of Dupuytren disease.