2026-07-23 デューク大学（Duke）
＜関連情報＞
- https://pratt.duke.edu/news/biomaterial-stroke-repair/
- https://www.sciencedirect.com/science/article/abs/pii/S3050562326001996
IL-4/C1q活性化アストロサイト由来細胞外小胞は末梢白血球を動員することにより脳卒中梗塞の回復を促進する IL-4/C1q activated astrocyte-derived extracellular vesicles promote stroke infarct recovery by recruiting peripheral leukocytes
Shangjing Xin, Lucy Zhang, Nhi V. Phan, Mengying An, Ligen Shi, S. Thomas Carmichael, Tatiana Segura
Cell Biomaterials Available online: 21 July 2026
DOI:https://doi.org/10.1016/j.celbio.2026.100543
Highlights
- Granular hydrogel retains and evenly distributes astrocyte EVs in stroke infarcts
- IL-4/C1q activation enriches astrocyte EV miRNA cargo associated with leukocyte adhesion
- IL-4/C1q EV-MAP recruits reparative macrophages and neutrophils into stroke infarct
- EV-MAP hydrogel enhances infarct regeneration and functional recovery after stroke
Summary
Regeneration of the necrotic infarct core is not currently a goal of clinical stroke therapies. However, restoring this region would be essential for complete and durable functional recovery after ischemic stroke. We engineered an injectable microporous annealed particle scaffold (MAPS) with covalently anchored extracellular vesicles (EVs) derived from primary astrocytes activated by IL-1α/TNF-α/C1q or IL-4/C1q, and delivered them into the infarct cavity of mice five days post-stroke. Only MAPS with IL-4/C1q-EVs induced robust revascularization, with perfused microvessels forming in the infarct center in 9 days, and motor function restored to near-baseline levels by 8 weeks. These regeneration and functional improvement were associated with selective recruitment of reparative neutrophils and macrophages into the infarct. Neutrophil depletion abrogated angiogenesis, demonstrating that neutrophils are required for mediating tissue repair. This immune-vascular crosstalk is associated with IL-4-induced enrichment of EV cargo, including adhesion- and angiogenesis-related miRNAs, such as miR-377-3p and miR-143-5p.
