Transforming Myofibroblasts Into Lipid-Filled Cells to Treat Dupuytren Disease

  • J Hand Surg Am. 2025 Apr 14:S0363-5023(25)00132-7. doi: 10.1016/j.jhsa.2025.03.005.
Mary E Ziegler  1 ,  Melinda Lem  1 ,  Jacklyn Melkonian  1 ,  Tania Nasrollahi  1 ,  Helia Rahimian  1 ,  Abtin Shams  1 ,  Nikhil Prabhakar  1 ,  Seyedeh Saina Saifzadeh  1 ,  Amalvin Fritz  1 ,  Amber Leis  2 ,  Alan Widgerow  3
Affiliations
  • 1. Center for Tissue Engineering, Department of Plastic Surgery, University of California, Orange, CA.
  • 2. Department of Plastic Surgery, University of California, Orange, CA.
  • 3. Center for Tissue Engineering, Department of Plastic Surgery, University of California, Orange, CA. Electronic address: [email protected].
PMID: 40232216 DOI: 10.1016/j.jhsa.2025.03.005
Abstract

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.

Keywords
Adipose-derived stem cells; Dupuytren disease; fibrosis; lipodystrophy; myofibroblasts.
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