Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Yea, Kyungmoo | - |
dc.contributor.author | Cho, Hanchae | - |
dc.contributor.author | Baek, Moon-Chang | - |
dc.date.accessioned | 2024-05-31T16:10:19Z | - |
dc.date.available | 2024-05-31T16:10:19Z | - |
dc.date.created | 2024-05-14 | - |
dc.date.issued | 2024-05-11 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/56619 | - |
dc.description.abstract | Nonalcoholic steatohepatitis (NASH) is a progressing liver ailment with an unmet need for effective therapies. Given the complex pathogenesis of NASH, there is a consensus towards combination therapy, emphasizing the development of combinations rather than monotherapies. Small extracellular vesicles (sEVs) exhibit efficient liver delivery and can be engineered to carry diverse therapeutic substances. This study affirms the potential utility of engineered sEVs as a NASH treatment. In this study, sEVs were engineered to display fibroblast growth factor 21 (FGF21) on their surface and enclose miR-223. Human liver cell lines were exposed to PBS, control sEVs, or engineered sEVs. Effects were examined through ICC, qPCR, and immunoblot analysis. To assess in vivo effects, C57BL/6 mice were subjected to a choline-deficient, L-amino acid-defined, high-fat diet for 10 weeks. Subsequently, mice were randomly assigned to receive vehicle, control sEV, engineered sEV, or FGF21 mimetics. The analysis included IHC, qPCR, immunoblot analysis, ELISA, and μCT. Introduction of engineered sEVs into human liver cell lines led to a significant reduction in basal lipid storage and the expression of fibrosis and inflammation markers. This effect extended to significant improvements even under stimulating conditions such as palmitate or TGFβ1. Administering engineered sEVs with an FGF21-blocking antibody or miR-223 inhibitor effectively mitigated the impact on steatosis, fibrosis, and inflammation, thereby validating the crucial roles of FGF21 and miR-223 in these processes. In an in vivo model, intravenously administered sEVs exhibited liver-targeted delivery, resulting in a notable reduction in the NASH phenotype, as well as steatosis, inflammation, and fibrosis. Our study establishes the promising therapeutic role of engineered sEVs displaying FGF21 on their surface and encapsulating miR-223 for NASH treatment. These sEVs demonstrate a multifaceted impact on NASH development, reducing lipid storage and suppressing fibrosis and inflammation markers in both in vitro and in vivo models. The liver-specific delivery of engineered sEVs offers strategic advantages, providing a comprehensive approach to attenuate NASH progression through diverse pathways. This study lays a robust foundation for further exploration and development of engineered sEVs as a transformative therapeutic modality in NASH treatment. | - |
dc.language | English | - |
dc.publisher | International Society for Extracellular Vesicles | - |
dc.title | Treatment of MASH utilizing engineered extracellular vesicles with surface-displayed FGF21 and encapsulated miR-223 | - |
dc.type | Conference Paper | - |
dc.identifier.bibliographicCitation | ISEV 2024 Annual Meeting | - |
dc.identifier.url | https://talley.eventsair.com/isev2024/program | - |
dc.citation.conferenceDate | 2024-05-08 | - |
dc.citation.conferencePlace | AT | - |
dc.citation.conferencePlace | Melbourne | - |
dc.citation.title | ISEV 2024 Annual Meeting | - |
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