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

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

This study elucidates the critical role of macrophage-myofibroblast transition (MMT) in the pathogenesis of intestinal fibrosis in Crohn's disease (CD). Through analysis of stricturing intestinal tissues from CD patients and TNBS-induced CD mouse models, we demonstrated that TGF-β1 activates the MAPK signalling pathway to induce MMT in macrophages (Mø), resulting in increased expression of α-SMA and collagen production. Importantly, these MMT-derived myofibroblasts secrete CCL17, which recruits CCR4 + regulatory T cells (Tregs) to fibrotic lesions, creating a pro-fibrotic microenvironment. Further investigation showed that the adoptive transfer of Mø exacerbated fibrosis in CD mice, whilst Mø depletion attenuated this process. Therapeutically, adipose-derived mesenchymal stromal cells-derived extracellular vesicles (AMSC-sEVs) could effectively deliver MFGE8 to inhibit MAPK activation, thereby suppressing MMT and reducing CCL17-mediated Treg recruitment. Treatment with AMSC-sEVs significantly improved intestinal fibrosis in CD mice, as evidenced by reduced collagen deposition and improved histological scores, whereas MFGE8 knockdown in AMSC-sEVs diminished these protective effects. These findings not only establish MMT as a key mechanism driving CD-associated intestinal fibrosis through the CCL17-CCR4 axis but also highlight AMSC-sEVs as a promising cell-free therapeutic strate

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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