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

  • Cell Rep Med. 2025 Apr 15;6(4):102079. doi: 10.1016/j.xcrm.2025.102079.
Xingyu Zhou  1 ,  Dingchao Zhu  1 ,  Di Wu  1 ,  Gaocai Li  1 ,  Huaizhen Liang  1 ,  Weifeng Zhang  1 ,  Yali Wu  2 ,  Hanpeng Xu  1 ,  Zhengdong Zhang  3 ,  Bide Tong  1 ,  Yu Song  1 ,  Kun Wang  1 ,  Xiaobo Feng  1 ,  Jie Lei  1 ,  Hongchuan Wang  1 ,  Xiaoguang Zhang  1 ,  Liang Ma  1 ,  Yuhang Chen  1 ,  Junyu Wei  1 ,  Zixuan Ou  1 ,  Shuchang Peng  1 ,  Xinghuo Wu  1 ,  Lei Tan  4 ,  Bingjin Wang  5 ,  Cao Yang  6
Affiliations
  • 1. Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 2. Hubei Province Key Laboratory of Biological Targeted Therapy, MOE Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 3. Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China.
  • 4. Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: [email protected].
  • 5. Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: [email protected].
  • 6. Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen 518057, China. Electronic address: [email protected].
PMID: 40199328 DOI: 10.1016/j.xcrm.2025.102079
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.

Keywords
BAI1; CAR-M; apoptosis; efferocytosis; inflammation; intervertebral disc degeneration; macrophage therapy; microneedle delivery; nucleus pulposus.
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