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

Jiaqi Xu; Chaoran Shi; Feifei Yuan; Yinghe Ding; Yong Xie; Yudong Liu; Fengzhang Zhu; Hongbin Lu; Chunyue Duan; Jianzhong Hu; Liyuan Jiang

Bioactive Materials (Feb 2024)

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

Jiaqi Xu,
Chaoran Shi,
Feifei Yuan,
Yinghe Ding,
Yong Xie,
Yudong Liu,
Fengzhang Zhu,
Hongbin Lu,
Chunyue Duan,
Jianzhong Hu,
Liyuan Jiang

Affiliations

Jiaqi Xu: Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
Chaoran Shi: Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
Feifei Yuan: Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
Yinghe Ding: Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
Yong Xie: Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
Yudong Liu: Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
Fengzhang Zhu: Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
Hongbin Lu: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
Chunyue Duan: Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
Jianzhong Hu: Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Corresponding author. Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China.
Liyuan Jiang: Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, Hunan Province, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China; Corresponding author. Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China.

Journal volume & issue: Vol. 32
pp. 427 – 444

Abstract

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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.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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