Dual-mode action of scalable, high-quality engineered stem cell-derived SIRPα-extracellular vesicles for treating acute liver failure

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Nature Communications Pub Date : 2025-02-23 DOI:10.1038/s41467-025-57133-w

Seohyun Kim, Yoon Kyoung Kim, Seonghyun Kim, Yong-Soon Choi, Inkyu Lee, Hyemin Joo, Jaehyun Kim, Minjeong Kwon, Seryoung Park, Min Kyoung Jo, Yoonjeong Choi, Theresa D’Souza, Jae Woong Jung, Elie Zakhem, Stephen Lenzini, Jiwan Woo, Hongyoon Choi, Jeongbin Park, Seung-Yoon Park, Gi Beom Kim, Gi-Hoon Nam, In-San Kim

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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.

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.