한빛사 논문
Dong Gil Youa,1, Byeong Hoon Oha,1, Van Quy Nguyena, Gyeong Taek Lima, Wooram Uma, Jae Min Junga, Jueun Jeona, Ji Suk Choib,c, Young Chan Choib,c, Youn Jae Jungb,c, Jungmi Leea, Dong-Gyu Joc,d,e, Yong Woo Chob,c, Jae Hyung Parka,c,e,*
aSchool of Chemical Engineering, College of Engineering, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea bDepartment of Chemical Engineering, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea cExoStemTech Inc., 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Republic of Korea dSchool of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea eBiomedical Institute for Convergence at SKKU (BICS), , Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea
1These authors contributed equally to this paper.
*Corresponding author.
Abstract
Allogeneic transplantation of mesenchymal stem cell-derived extracellular vesicles (EVs) offers great potential for treating liver fibrosis. However, owing to their intrinsic surface characteristics, bare EVs are non-specifically distributed in the liver tissue after systemic administration, leading to limited therapeutic efficacy. To target activated hepatic stellate cells (HSCs), which are responsible for hepatic fibrogenesis, vitamin A-coupled small EVs (V-EVs) were prepared by incorporating vitamin A derivative into the membrane of bare EVs. No significant differences were found in the particle size and morphology between bare and V-EVs. In addition, surface engineering of EVs did not affect the expression of surface marker proteins (e.g., CD63 and CD9), as demonstrated by flow cytometry. Owing to the surface incorporation of vitamin A, V-EVs were selectively taken up by activated HSCs via receptor-mediated endocytosis. When systemically administered to mice with liver fibrosis, V-EVs effectively targeted activated HSCs in the liver tissue, resulting in reversal of the fibrotic cascade. Consequently, even at a 10-fold lower dose, V-EVs exhibited comparable anti-fibrotic effects to those of bare EVs, substantiating their therapeutic potential for liver fibrosis.
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