2. Academic Validation
  3. Transforming Myofibroblasts Into Lipid-Filled Cells to Treat Dupuytren Disease

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

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: awidgero@hs.uci.edu.
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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