PMID- 33960559 OWN - NLM STAT- MEDLINE DCOM- 20210614 LR - 20210614 IS - 1365-2184 (Electronic) IS - 0960-7722 (Print) IS - 0960-7722 (Linking) VI - 54 IP - 6 DP - 2021 Jun TI - Transplantation of tauroursodeoxycholic acid-inducing M2-phenotype macrophages promotes an anti-neuroinflammatory effect and functional recovery after spinal cord injury in rats. PG - e13050 LID - 10.1111/cpr.13050 [doi] LID - e13050 AB - OBJECTIVES: In 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. METHODS: To 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. RESULTS: The 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. CONCLUSIONS: This 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. CI - (c) 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd. FAU - Han, Gong Ho AU - Han GH AD - Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si, Korea. AD - Department of Biomedical Science, CHA University, Seongnam-si, Korea. FAU - Kim, Seong Jun AU - Kim SJ AD - Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si, Korea. AD - Department of Biomedical Science, CHA University, Seongnam-si, Korea. FAU - Ko, Wan-Kyu AU - Ko WK AD - Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si, Korea. AD - Department of Biomedical Science, CHA University, Seongnam-si, Korea. FAU - Lee, Daye AU - Lee D AD - Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si, Korea. AD - Department of Biomedical Science, CHA University, Seongnam-si, Korea. FAU - Han, In-Bo AU - Han IB AD - Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si, Korea. FAU - Sheen, Seung Hun AU - Sheen SH AD - Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si, Korea. FAU - Hong, Je Beom AU - Hong JB AD - Department of Neurosurgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. FAU - Sohn, Seil AU - Sohn S AUID- ORCID: 0000-0001-5724-8099 AD - Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si, Korea. LA - eng GR - NRF-2020R1F1A1069875/the National Research Foundation of Korea (NRF)/ GR - the Ministry of Science, ICT and future Planning/ PT - Journal Article DEP - 20210507 PL - England TA - Cell Prolif JT - Cell proliferation JID - 9105195 RN - 516-35-8 (Taurochenodeoxycholic Acid) RN - 60EUX8MN5X (ursodoxicoltaurine) SB - IM MH - Animals MH - Cells, Cultured MH - Female MH - Inflammation/metabolism/physiopathology/therapy MH - Macrophages/metabolism/*transplantation MH - Rats MH - Rats, Sprague-Dawley MH - Recovery of Function MH - Spinal Cord Injuries/metabolism/physiopathology/*therapy MH - Taurochenodeoxycholic Acid/*metabolism PMC - PMC8168422 OTO - NOTNLM OT - bone marrow-derived macrophages OT - neuroinflammation OT - spinal cord injuries OT - tauroursodeoxycholic acid OT - transplantation COIS- The authors declare no competing financial interest. EDAT- 2021/05/08 06:00 MHDA- 2021/06/16 06:00 PMCR- 2021/05/07 CRDT- 2021/05/07 09:11 PHST- 2021/03/25 00:00 [revised] PHST- 2021/01/27 00:00 [received] PHST- 2021/04/13 00:00 [accepted] PHST- 2021/05/08 06:00 [pubmed] PHST- 2021/06/16 06:00 [medline] PHST- 2021/05/07 09:11 [entrez] PHST- 2021/05/07 00:00 [pmc-release] AID - CPR13050 [pii] AID - 10.1111/cpr.13050 [doi] PST - ppublish SO - Cell Prolif. 2021 Jun;54(6):e13050. doi: 10.1111/cpr.13050. Epub 2021 May 7.