Kim, Seohyun Kim, Yoon Kyoung Kim, Seonghyun Choi, Yong-Soon Lee, Inkyu Joo, Hyemin Kim, Jaehyun Kwon, Minjeong Park, Seryoung Jo, Min Kyoung Choi, Yoonjeong D'Souza, Theresa Jung, Jae Woong Zakhem, Elie Lenzini, Stephen Woo, Jiwan Choi, Hongyoon Park, Jeongbin Park, Seung-Yoon Kim, Gi Beom Nam, Gi-Hoon Kim, In-San 2025-03-23T12:00:37Z 2025-03-23T12:00:37Z 2025-03-19 2025-02 https://pubs.kist.re.kr/handle/201004/152089 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. English Nature Publishing Group Dual-mode action of scalable, high-quality engineered stem cell-derived SIRPα-extracellular vesicles for treating acute liver failure Article 10.1038/s41467-025-57133-w 1 Nature Communications, v.16, no.1 Nature Communications 16 1 Y scie scopus 001428519400008 2-s2.0-85218496094 Multidisciplinary Sciences Science & Technology - Other Topics Article SCALE