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

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

机构地区：[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

出　　处：《Bioactive Materials》2024年第2期427-444,共18页生物活性材料（英文）

基　　金：supported by the Key Program of the National Natural Science Foundation of China(No.82030071);the National Natural Science Foundation of China(No.82202722,No.81874004);the Science and Technology Major Project of Changsha(No.kh2103008);the Science Foundation of Xiangya Hospital for Young Scholar(Grant No.2021q18);the Natural Science Foundation of Changsha city(Grant No.kq2202378);Graduate students of Central South University independently explore innovative projects(2022ZZTS094).

摘　　要：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.

关 键 词：Spinal cord injury(SCI) Mitochondrial transplantation MACROPHAGE PHAGOCYTOSIS Targeted therapy 

分 类 号：R318[医药卫生—生物医学工程] R392[医药卫生—基础医学]