PMID- 31779687 OWN - NLM STAT- MEDLINE DCOM- 20200721 LR - 20211001 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 10 IP - 1 DP - 2019 Nov 28 TI - The TRIM protein Mitsugumin 53 enhances survival and therapeutic efficacy of stem cells in murine traumatic brain injury. PG - 352 LID - 10.1186/s13287-019-1433-4 [doi] LID - 352 AB - BACKGROUND: Traumatic brain injury (TBI) is a common neurotrauma leading to brain dysfunction and death. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold promise in the treatment of TBI. However, their efficacy is modest due to low survival and differentiation under the harsh microenvironment of the injured brain. MG53, a member of TRIM family protein, plays a vital role in cell and tissue damage repair. The present study aims to test whether MG53 preserves hUC-MSCs against oxidative stress and enhances stem cell survival and efficacy in TBI treatment. METHODS: In this study, we performed a series of in vitro and in vivo experiments in hUC-MSCs and mice to define the function of MG53 enhancing survival, neurogenesis, and therapeutic efficacy of stem cells in murine traumatic brain injury. RESULTS: We found that recombinant human MG53 (rhMG53) protein protected hUC-MSCs against H(2)O(2)-induced oxidative damage and stimulated hUC-MSC proliferation and migration. In a mouse model of contusion-induced TBI, intravenous administration of MG53 protein preserved the survival of transplanted hUC-MSCs, mitigated brain edema, reduced neurological deficits, and relieved anxiety and depressive-like behaviors. Co-treatment of MG53 and hUC-MSCs enhanced neurogenesis by reducing apoptosis and improving PI3K/Akt-GSK3beta signaling. CONCLUSION: MG53 enhances the efficacy of hUC-MSCs in the recovery of TBI, indicating that such adjunctive therapy may provide a novel strategy to lessen damage and optimize recovery for brain injury. FAU - Guan, Fangxia AU - Guan F AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. AD - The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. AD - Henan Provincial People's Hospital, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China. FAU - Huang, Tuanjie AU - Huang T AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. FAU - Wang, Xinxin AU - Wang X AD - The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. FAU - Xing, Qu AU - Xing Q AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. FAU - Gumpper, Kristyn AU - Gumpper K AD - Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA. FAU - Li, Peng AU - Li P AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. FAU - Song, Jishi AU - Song J AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. FAU - Tan, Tao AU - Tan T AD - Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA. FAU - Yang, Greta Luyuan AU - Yang GL AD - Stuyvesant High School, 345 Chambers St, New York, NY, 10282, USA. FAU - Zang, Xingxing AU - Zang X AD - Department of Microbiology and Immunology, Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA. FAU - Zhang, Jiewen AU - Zhang J AD - Henan Provincial People's Hospital, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China. FAU - Wang, Yuming AU - Wang Y AD - Henan Provincial People's Hospital, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China. FAU - Yang, Yunlei AU - Yang Y AD - Department of Medicine and Neuroscience, Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA. FAU - Liu, Yashi AU - Liu Y AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. FAU - Zhang, Yanting AU - Zhang Y AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. FAU - Yang, Bo AU - Yang B AD - The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. FAU - Ma, Jianjie AU - Ma J AD - Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA. Jianjie.Ma@osumc.edu. FAU - Ma, Shanshan AU - Ma S AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. mashanshan84@163.com. LA - eng GR - R01 AR061385/AR/NIAMS NIH HHS/United States GR - R01 AR070752/AR/NIAMS NIH HHS/United States GR - R01 DK106394/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191128 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (TRIM72 protein, human) RN - 0 (Tripartite Motif Proteins) SB - IM EIN - Stem Cell Res Ther. 2021 Sep 30;12(1):522. PMID: 34593038 MH - Animals MH - *Brain Injuries, Traumatic/metabolism/pathology/therapy MH - Cell Survival MH - Disease Models, Animal MH - Heterografts MH - Humans MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - *Mesenchymal Stem Cells/metabolism/pathology MH - Mice MH - *Oxidative Stress MH - *Signal Transduction MH - Tripartite Motif Proteins/*metabolism MH - *Umbilical Cord/metabolism/pathology PMC - PMC6883632 OTO - NOTNLM OT - Mitsugumin 53 OT - Neuroprotection OT - PI3K-Akt-GSK3beta OT - Stem cells OT - Traumatic brain injury COIS- The authors declare that they have no competing interests. EDAT- 2019/11/30 06:00 MHDA- 2020/07/22 06:00 PMCR- 2019/11/28 CRDT- 2019/11/30 06:00 PHST- 2019/03/18 00:00 [received] PHST- 2019/09/30 00:00 [accepted] PHST- 2019/07/22 00:00 [revised] PHST- 2019/11/30 06:00 [entrez] PHST- 2019/11/30 06:00 [pubmed] PHST- 2020/07/22 06:00 [medline] PHST- 2019/11/28 00:00 [pmc-release] AID - 10.1186/s13287-019-1433-4 [pii] AID - 1433 [pii] AID - 10.1186/s13287-019-1433-4 [doi] PST - epublish SO - Stem Cell Res Ther. 2019 Nov 28;10(1):352. doi: 10.1186/s13287-019-1433-4.