Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis

Mesenchymal stromal cells (MSCs) are used for ameliorating liver fibrosis and aiding liver regeneration after cirrhosis; Here, we analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs). γ-sEVs effectively induced anti...

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Bibliographic Details
Published in:npj Regenerative medicine 2021-03, Vol.6 (1), p.19-19, Article 19
Main Authors: Takeuchi, Suguru, Tsuchiya, Atsunori, Iwasawa, Takahiro, Nojiri, Shunsuke, Watanabe, Takayuki, Ogawa, Masahiro, Yoshida, Tomoaki, Fujiki, Katsunori, Koui, Yuta, Kido, Taketomo, Yoshioka, Yusuke, Fujita, Mayu, Kikuta, Junichi, Itoh, Tohru, Takamura, Masaaki, Shirahige, Katsuhiko, Ishii, Masaru, Ochiya, Takahiro, Miyajima, Atsushi, Terai, Shuji
Format: Article
Language:English
Subjects:
631/532/2074
631/532/2118/2074
Biomaterials
Biomedical and Life Sciences
Biomedicine
Cell Biology
Extracellular vesicles
Immunology
Liver
Liver cirrhosis
Regenerative Medicine/Tissue Engineering
Stem Cells
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Summary:Mesenchymal stromal cells (MSCs) are used for ameliorating liver fibrosis and aiding liver regeneration after cirrhosis; Here, we analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs). γ-sEVs effectively induced anti-inflammatory macrophages with high motility and phagocytic abilities in vitro, while not preventing hepatic stellate cell (HSC; the major source of collagen fiber) activation in vitro. The proteome analysis of MSC-derived sEVs revealed anti-inflammatory macrophage inducible proteins (e.g., annexin-A1, lactotransferrin, and aminopeptidase N) upon IFN-γ stimulation. Furthermore, by enabling CX 3 CR1+ macrophage accumulation in the damaged area, γ-sEVs ameliorated inflammation and fibrosis in the cirrhosis mouse model more effectively than sEVs. Single cell RNA-Seq analysis revealed diverse effects, such as induction of anti-inflammatory macrophages and regulatory T cells, in the cirrhotic liver after γ-sEV administration. Overall, IFN-γ pre-conditioning altered sEVs resulted in efficient tissue repair indicating a new therapeutic strategy.
ISSN:2057-3995
2057-3995
DOI:10.1038/s41536-021-00132-4