Microneedle delivery of CAR-M-like engineered macrophages alleviates intervertebral disc degeneration through enhanced efferocytosis capacity.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-04-02 DOI:10.1016/j.xcrm.2025.102079

Xingyu Zhou, Dingchao Zhu, Di Wu, Gaocai Li, Huaizhen Liang, Weifeng Zhang, Yali Wu, Hanpeng Xu, Zhengdong Zhang, Bide Tong, Yu Song, Kun Wang, Xiaobo Feng, Jie Lei, Hongchuan Wang, Xiaoguang Zhang, Liang Ma, Yuhang Chen, Junyu Wei, Zixuan Ou, Shuchang Peng, Xinghuo Wu, Lei Tan, Bingjin Wang, Cao Yang

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引用次数: 0

Abstract

Macrophages eliminate apoptotic cells produced daily in the body through efferocytosis. Restricted clearance can cause inflammation-related diseases. In intervertebral discs (IVDs), apoptotic nucleus pulposus cells (NPCs) are difficult to effectively remove, and their accumulation can cause changes in the inflammatory microenvironment, disrupt IVD homeostasis, and lead to IVD degeneration (IDD). Here, we present chimeric antigen receptor-M-like engineered macrophages (CAR-eMs) with enhanced efferocytosis capacity for IDD treatment. Macrophages undergo phenotypic transformation and a reduction in phagocytic ability after phagocyting apoptotic NPCs, but their efferocytosis capacity recovers with upregulated brain-specific angiogenesis inhibitor 1 (BAI1) expression. We develop a CAR-eM system with enhanced BAI1 expression and an IVD circular microneedle (MN) delivery system that utilizes arrays of MNs to deliver CAR-eMs into the deep IVD layers, thereby clearing apoptotic NPCs, ameliorating the inflammatory microenvironment, and repairing damaged IVDs. Our study explores the therapeutic potential of CAR-eM efferocytosis for IDD treatment.

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微针输送car - m样工程巨噬细胞通过增强efferocytosis能力减轻椎间盘退变。

巨噬细胞通过efferocytosis消除体内每天产生的凋亡细胞。限制清除可引起炎症相关疾病。在椎间盘（IVD）中，凋亡的髓核细胞（NPCs）难以有效清除，其积累可引起炎症微环境的改变，破坏IVD内稳态，导致IVD退变（IDD）。在这里，我们提出嵌合抗原受体- m样工程巨噬细胞（CAR-eMs）具有增强的efferocytosis能力，用于治疗IDD。吞噬凋亡的npc后，巨噬细胞发生表型转化，吞噬能力降低，但随着脑特异性血管生成抑制剂1 （brain-specific angiogenesis inhibitor 1, BAI1）表达上调，巨噬细胞的efferocysis能力恢复。我们开发了一种增强BAI1表达的CAR-eM系统和一种IVD圆形微针（MN）递送系统，该系统利用MNs阵列将CAR-eM递送到IVD深层层，从而清除凋亡的NPCs，改善炎症微环境，修复受损的IVD。我们的研究探讨了CAR-eM efferocytosis在IDD治疗中的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.