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AMSC-sEVs Ameliorated Crohn's Disease by Inhibiting Macrophage-Myofibroblast Transition Through the Delivery of MFGE8

Minghao Xie1, Qiang Liu1, Zhizhong Xiong2

  • 1Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Cell Proliferation
|January 3, 2026
PubMed

Insights

Macrophage-myofibroblast transition drives intestinal fibrosis in Crohn's disease by promoting a pro-fibrotic environment. Adipose-derived mesenchymal stromal cell-derived extracellular vesicles show therapeutic potential by inhibiting this transition.

Area of Science:

  • Gastroenterology and Immunology
  • Fibrosis Research
  • Cellular Biology

Background:

  • Intestinal fibrosis is a major complication of Crohn's disease (CD), significantly impacting patient quality of life.
  • The precise mechanisms driving fibrosis in CD, particularly the role of immune cells, require further elucidation.
  • Macrophage-myofibroblast transition (MMT) has emerged as a potential contributor to fibrotic processes.

Purpose of the Study:

  • To investigate the role of macrophage-myofibroblast transition (MMT) in Crohn's disease (CD) intestinal fibrosis.
  • To identify the molecular pathways and cellular interactions involved in MMT-driven fibrosis.
  • To evaluate the therapeutic potential of adipose-derived mesenchymal stromal cells-derived extracellular vesicles (AMSC-sEVs) in mitigating CD-associated fibrosis.

Main Methods:

  • Analysis of human CD intestinal tissues and a TNBS-induced mouse model of CD.
  • Investigated the role of TGF-β1, MAPK signaling, and α-SMA expression in MMT.
  • Assessed the recruitment of regulatory T cells (Tregs) via the CCL17-CCR4 axis.
  • Utilized adoptive transfer and depletion of macrophages (Mø) to study Mø involvement.
  • Administered AMSC-sEVs loaded with MFGE8 as a therapeutic intervention.

Main Results:

  • TGF-β1 induces MMT in macrophages via the MAPK pathway, increasing α-SMA and collagen.
  • MMT-derived myofibroblasts secrete CCL17, recruiting CCR4+ Tregs and promoting a pro-fibrotic microenvironment.
  • Macrophage transfer exacerbated fibrosis, while Mø depletion attenuated it in CD models.
  • AMSC-sEVs delivered MFGE8, inhibiting MAPK, suppressing MMT, and reducing Treg recruitment.
  • AMSC-sEV treatment significantly improved intestinal fibrosis in CD mice, reducing collagen deposition.

Conclusions:

  • MMT is a critical mechanism in Crohn's disease intestinal fibrosis, mediated by the CCL17-CCR4 axis.
  • Macrophage-derived myofibroblasts play a key role in establishing a pro-fibrotic environment.
  • AMSC-sEVs represent a promising cell-free therapeutic strategy for targeting MMT and reducing intestinal fibrosis in CD.
Keywords:
Crohn's diseaseMFGE8Tregsmacrophagesmacrophage‐myofibroblast transition

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