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Transplantation of tauroursodeoxycholic acid–inducing M2‐phenotype macrophages promotes an anti‐neuroinflammatory effect and functional recovery after spinal cord injury in rats
Authors:Gong Ho Han,Seong Jun Kim,Wan‐  Kyu Ko,Daye Lee,In‐  Bo Han,Seung Hun Sheen,Je Beom Hong,Seil Sohn
Affiliation:1. Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam‐si Korea ; 2. Department of Biomedical Science, CHA University, Seongnam‐si Korea ; 3. Department of Neurosurgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul Korea
Abstract:ObjectivesIn this study, we study the transplantation of tauroursodeoxycholic acid (TUDCA)‐induced M2‐phenotype (M2) macrophages and their ability to promote anti‐neuroinflammatory effects and functional recovery in a spinal cord injury (SCI) model.MethodsTo this end, compared to the granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), we evaluated whether TUDCA effectively differentiates bone marrow–derived macrophages (BMDMs) into M2 macrophages.ResultsThe M2 expression markers in the TUDCA‐treated BMDM group were increased more than those in the GM‐CSF‐treated BMDM group. After the SCI and transplantation steps, pro‐inflammatory cytokine levels and the mitogen‐activated protein kinase (MAPK) pathway were significantly decreased in the TUDCA‐induced M2 group more than they were in the GM‐CSF‐induced M1 group and in the TUDCA group. Moreover, the TUDCA‐induced M2 group showed significantly enhanced tissue volumes and improved motor functions compared to the GM‐CSF‐induced M1 group and the TUDCA group. In addition, biotinylated dextran amine (BDA)–labelled corticospinal tract (CST) axons and neuronal nuclei marker (NeuN) levels were increased in the TUDCA‐induced M2 group more than those in the GM‐CSF‐induced M1 group and the TUDCA group.ConclusionsThis study demonstrates that the transplantation of TUDCA‐induced M2 macrophages promotes an anti‐neuroinflammatory effect and motor function recovery in SCI. Therefore, we suggest that the transplantation of TUDCA‐induced M2 macrophages represents a possible alternative cell therapy for SCI.
Keywords:bone marrow–  derived macrophages, neuroinflammation, spinal cord injuries, tauroursodeoxycholic acid, transplantation
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