Table 1.
Effect of MSC-EVs on SSc.
| Source of MSCs | Experiment models | Properties of MSC-EVs | Mechanisms | References | |
|---|---|---|---|---|---|
| 1 | Human umbilical cord | Bleomycin-induced mouse model | Antifibrosis | Reduction of deposition of extracellular matrix and inhibition of the epithelial–mesenchymal transition process |
(64) |
| Immunomodulation | Facilitating M1 macrophage polarization and suppressing M2 macrophage polarization, leading to the restoration of the balance of M1/M2 macrophages | ||||
| 2 | Adipose tissue | TGF-β1-induced model of human myofibroblasts | Antifibrosis | ASC-EVs can better improve anti-fibrotic and pro-remodeling functions than ASCs in vitro | (65) |
| 3 | Bone marrow | HOCl-induced murine model | Antifibrosis | IFN-γ-pre-activation improved the therapeutic effects of MSC-EV in the SSc model. Low doses of IFN-γ decreased the expression of fibrotic markers, while high doses improved remodeling markers in vivo | (66) |
| Immunomodulation | High dose of IFN-γ-pre-activation upregulated anti-inflammatory markers in MSC-EV, including iNos, IL1ra, and IL-6 in vivo | ||||
| 4 | Bone marrow | Bleomycin-induced dermal fibrosis in mice | Antifibrosis | Inhibition of collagen type I expression by miR-196b-5p in exosomes might be one of the mechanisms by which MSCs suppress skin fibrosis in vivo | (67) |
| 5 | Bone marrow | Bleomycin-induced dermal fibrosis in mice | Antifibrosis | The intervention of fibrosis of the SSC model by miRNAs they carry and regulate the WNT and TGF-β signaling pathways | (68) |
| Immunomodulation | Reduction of the numbers of mast cells and infiltrating macrophages and lymphocytes, and the levels of the inflammatory cytokines IL-6, IL-10, and Tnf-α in BLM-treated mice | ||||
| 6 | Human umbilical cord | Bleomycin-induced dermal fibrosis in mice | Antifibrosis | Attenuating myofibroblast activation and collagen deposition in dermal fibrosis by downregulating the TGF-β/Smad signaling pathway in vivo | (64) |
| 7 | Human adipose tissue | HOCl-induced SSc model | Antifibrosis | Alleviating SSc and regulating methylation and apoptosis via miR-29a-3p | (69) |
| 8 | Human umbilical cord | cGVHD mouse model | Immunomodulation | Suppressing the activation of macrophages and B-cell immune response | (70) |
MSC-EVs, mesenchymal stem cell-derived extracellular vesicles; SSc, systemic sclerosis; MSCs, mesenchymal stem cells; ASCs, adipose tissue-derived mesenchymal stem cells; HOCl, hypochlorous acid; BLM, bleomycin; cGVHD, chronic graft-versus-host disease.