The TRIM protein Mitsugumin 53 enhances survival and therapeutic efficacy of stem cells in murine traumatic brain injury
Authors: Greta Luyuan Yang
Bo Yang
Shanshan Ma
Jianjie Ma
Xingxing Zang
Yunlei Yang
Jiewen Zhang
Tuanjie Huang
Fangxia Guan
Qu Xing
Yanting Zhang
Jishi Song
Tao Tan
Xinxin Wang
Yuming Wang
Kristyn Gumpper
Yashi Liu
Peng Li
Journal: Stem Cell Research & Therapy (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Mitsugumin 53; Neuroprotection; PI3K-Akt-GSK3β; Stem cells; Traumatic brain injury.
Affiliations: School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China., The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China., Henan Provincial People's Hospital, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China., Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA., Stuyvesant High School, 345 Chambers St, New York, NY, 10282, USA., Department of Microbiology and Immunology, Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA., Department of Medicine and Neuroscience, Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA., Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA. ., School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. .

Abstract:  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 H2O2-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-GSK3β 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. 

Retracted: No

PubPeer comments:
 Two images in figure 2G appear to overlap. *** Contrast enhanced ![file] , 
 Dear Dr. Biskrensis, Thank you very much. We are checking this error you mentioned above and will provide a response here and to the journal as soon as possible. Best regards, Shanshan Ma , 
 Dear Dr. Biskrensis, We appreciate your comments. Upon receiving your information, we re-examined the original data and raw records very carefully. The representative images of Fig.2g we chose from several repetitions, but happened to overlap field of vision inadvertently. We are very sorry for uploading the wrong figure unintentionally. The correct Fig.2g is presented here. In addition, we also wrote to the editor of the journal for a correction request. We state that this mistake will not affect the conclusions of this work. We apologize for any confusion this unintentional error might have caused. Thanks a lot. Yours sincerely, Shanshan Ma ![file] , 
 Correction published: 30 September 2021 The original article [1] contained errors in Figs. 2 and 5. ![file] ![file] In Fig. 2G, the representative SA-u03b2-gal staining image of H2O2 group was mistakenly used for the MG53u2009+u2009H2O2 group during assembly of the figure. In Fig. 5H, the typical NeuN immunofluorescence staining image of MG53 was mistakenly used for the TBI group during assembly of the figure. The authors have provided the correct figures and also reanalyzed the quantification of SA-u03b2-gal staining (Fig. 2i) and NeuN immunofluorescence staining (Fig. 5 k). The authors state that these mistakes do not affect the conclusion of the article. ,