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

Xingyu Zhou1, Dingchao Zhu1, Di Wu1

  • 1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Cell Reports. Medicine
|April 8, 2025
PubMed

Insights

Engineered macrophages with enhanced efferocytosis clear apoptotic cells in intervertebral discs (IVDs). This novel approach using chimeric antigen receptor-M-like engineered macrophages (CAR-eMs) offers a promising treatment for intervertebral disc degeneration (IDD).

Area of Science:

  • Immunology
  • Regenerative Medicine
  • Biomaterials

Background:

  • Macrophages perform efferocytosis to clear apoptotic cells, preventing inflammation-related diseases.
  • Accumulation of apoptotic nucleus pulposus cells (NPCs) in intervertebral discs (IVDs) disrupts homeostasis and causes intervertebral disc degeneration (IDD).
  • Macrophage efferocytic capacity diminishes after phagocytosing NPCs, hindering effective clearance in IVDs.

Purpose of the Study:

  • To develop engineered macrophages with enhanced efferocytosis for treating IDD.
  • To investigate the role of brain-specific angiogenesis inhibitor 1 (BAI1) in macrophage efferocytosis recovery.
  • To create a novel delivery system for engineered macrophages into deep IVD layers.

Main Methods:

  • Development of chimeric antigen receptor-M-like engineered macrophages (CAR-eMs) with upregulated BAI1 expression.
  • Design of a circular microneedle (MN) delivery system for targeted CAR-eM delivery into IVDs.
  • Evaluation of CAR-eM efferocytosis capacity and therapeutic efficacy in an IDD model.

Main Results:

  • CAR-eMs demonstrated enhanced efferocytosis of apoptotic NPCs.
  • Upregulated BAI1 expression restored and enhanced macrophage efferocytic function.
  • The MN delivery system successfully delivered CAR-eMs to deep IVD layers, clearing apoptotic NPCs.
  • Treatment with CAR-eMs ameliorated the inflammatory microenvironment and promoted IVD repair.

Conclusions:

  • Engineered macrophages (CAR-eMs) with enhanced BAI1 expression show significant potential for treating IDD by improving efferocytosis.
  • The microneedle delivery system provides an effective method for targeted delivery of therapeutic macrophages into the IVD.
  • This study presents a promising cell-based therapy for intervertebral disc degeneration by leveraging enhanced efferocytosis.
Keywords:
BAI1CAR-Mapoptosisefferocytosisinflammationintervertebral disc degenerationmacrophage therapymicroneedle deliverynucleus pulposus

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