2. Academic Validation
  3. Targeted transplantation of engineered mitochondrial compound promotes functional recovery after spinal cord injury by enhancing macrophage phagocytosis

Targeted transplantation of engineered mitochondrial compound promotes functional recovery after spinal cord injury by enhancing macrophage phagocytosis

  • Bioact Mater. 2023 Oct 27:32:427-444. doi: 10.1016/j.bioactmat.2023.10.016.
Jiaqi Xu 1 2 3,  Chaoran Shi 1 2 3,  Feifei Yuan 1 2 3,  Yinghe Ding 1 2 3,  Yong Xie 1 2 3,  Yudong Liu 1 2 3,  Fengzhang Zhu 1 2 3,  Hongbin Lu 2 3 4,  Chunyue Duan 1 2 3,  Jianzhong Hu 1 2 3,  Liyuan Jiang 1 2 3
Affiliations

Affiliations

  • 1 Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China.
  • 2 Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China.
  • 3 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China.
  • 4 Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China.
PMID: 37954465 DOI: 10.1016/j.bioactmat.2023.10.016
Abstract

Mitochondria are crucial in sustaining and orchestrating cellular functions. Capitalizing on this, we explored mitochondrial transplantation as an innovative therapeutic strategy for acute spinal cord injury (SCI). In our study, we developed an engineered mitochondrial compound tailored to target macrophages within the SCI region. Sourced from IL-10-induced Mertkhi bone marrow-derived macrophages, we conjugated a peptide sequence, cations-cysteine-alanine-glutamine-lysine (CAQK), with the mitochondria, optimizing its targeting affinity for the injury site. Our data demonstrated that these compounds significantly enhanced macrophage phagocytosis of myelin debris, curtailed lipid buildup, ameliorated mitochondrial dysfunction, and attenuated pro-inflammatory profiles in macrophages, both in vitro and in vivo. The intravenously delivered mitochondrial compounds targeted the SCI epicenter, with macrophages being the primary recipients. Critically, they promoted tissue regeneration and bolstered functional recovery in SCI mice. This study heralds a transformative approach to mitochondrial transplantation in SCI, spotlighting the modulation of macrophage activity, phagocytosis, and phenotype.

Keywords

Macrophage; Mitochondrial transplantation; Phagocytosis; Spinal cord injury (SCI); Targeted therapy.

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