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Nat. Commun., Published: 23 February 2025 | https://doi.org/10.1038/s41467-025-57133-w
Dual-mode action of scalable, high-quality engineered stem cell-derived SIRPα-extracellular vesicles for treating acute liver failure
Seohyun Kim1,10, Yoon Kyoung Kim1,10, Seonghyun Kim1, Yong-Soon Choi1, Inkyu Lee1,2, Hyemin Joo1,2, Jaehyun Kim1, Minjeong Kwon3, Seryoung Park3, Min Kyoung Jo3, Yoonjeong Choi1, Theresa D’Souza4, Jae Woong Jung4, Elie Zakhem4, Stephen Lenzini4, Jiwan Woo5, Hongyoon Choi6,7, Jeongbin Park7, Seung-Yoon Park8, Gi Beom Kim1, Gi-Hoon Nam1,3 & In-San Kim2,9
1SHIFTBIO INC, Seoul, Republic of Korea.
2KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea.
3Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, Republic of Korea.
4RoosterBio, Inc, Frederick, MD, USA.
5Research Animal Resource Center, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
6Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
7Portrai, Inc, Seoul, Republic of Korea.
8Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju, Republic of Korea.
9Chemical and Biological Integrative Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
10These authors contributed equally: Seohyun Kim, Yoon Kyoung Kim.
Corresponding authors
Correspondence to Gi Beom Kim, Gi-Hoon Nam or In-San Kim.
1SHIFTBIO INC, Seoul, Republic of Korea.
2KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea.
3Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, Republic of Korea.
4RoosterBio, Inc, Frederick, MD, USA.
5Research Animal Resource Center, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
6Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
7Portrai, Inc, Seoul, Republic of Korea.
8Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju, Republic of Korea.
9Chemical and Biological Integrative Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
10These authors contributed equally: Seohyun Kim, Yoon Kyoung Kim.
Corresponding authors
Correspondence to Gi Beom Kim, Gi-Hoon Nam or In-San Kim.
Abstract
Acute liver failure (ALF) is a life-threatening condition caused by rapid hepatocyte death and impaired liver regeneration. Here we show that extracellular vesicles engineered to express Signal Regulatory Protein Alpha (SIRP-EVs), produced via a scalable 3D bioreactor process with high yield and purity, exhibit significant therapeutic potential by targeting damaged cells and promoting tissue repair. SIRP-EVs block CD47, a crucial inhibitory signal on necroptotic cells, to enhance macrophage-mediated clearance of dying hepatocytes. They also deliver regenerative cargo from mesenchymal stem cells, reprogramming macrophages to support liver regeneration. In male animal models, SIRP-EVs significantly reduce liver injury markers and improve survival, demonstrating their dual-function therapeutic efficacy. By integrating the resolution of necroptosis with regenerative macrophage reprogramming, SIRP-EVs represent a promising platform for restoring liver function. These findings support the development of EV-based in vivo macrophage reprogramming therapies for ALF and other inflammation-driven diseases, paving the way for the clinical application of engineered EV therapeutics.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-24)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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