The TRIM protein Mitsugumin 53 enhances survival and therapeutic efficacy of stem cells in murine traumatic brain injury

Fangxia Guan, Tuanjie Huang, Xinxin Wang, Qu Xing, Kristyn Gumpper, Peng Li, Jishi Song, Tao Tan, Greta Luyuan Yang, Xingxing Zang, Jiewen Zhang, Yuming Wang, Yunlei Yang, Yashi Liu, Yanting Zhang, Bo Yang, Jianjie Ma, Shanshan Ma

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number352
JournalStem Cell Research and Therapy
Volume10
Issue number1
DOIs
StatePublished - Nov 28 2019

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Umbilical Cord
Stem cells
Mesenchymal Stromal Cells
Brain
Stem Cells
Survival
Proteins
Neurogenesis
Therapeutics
Brain Death
Tripartite Motif Proteins
Traumatic Brain Injury
Contusions
Brain Edema
Recovery
Phosphatidylinositol 3-Kinases
Oxidative stress
Intravenous Administration
Brain Injuries
Cell Movement

Keywords

  • Mitsugumin 53
  • Neuroprotection
  • PI3K-Akt-GSK3β
  • Stem cells
  • Traumatic brain injury

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology

Cite this

The TRIM protein Mitsugumin 53 enhances survival and therapeutic efficacy of stem cells in murine traumatic brain injury. / Guan, Fangxia; Huang, Tuanjie; Wang, Xinxin; Xing, Qu; Gumpper, Kristyn; Li, Peng; Song, Jishi; Tan, Tao; Yang, Greta Luyuan; Zang, Xingxing; Zhang, Jiewen; Wang, Yuming; Yang, Yunlei; Liu, Yashi; Zhang, Yanting; Yang, Bo; Ma, Jianjie; Ma, Shanshan.

In: Stem Cell Research and Therapy, Vol. 10, No. 1, 352, 28.11.2019.

Research output: Contribution to journalArticle

Guan, F, Huang, T, Wang, X, Xing, Q, Gumpper, K, Li, P, Song, J, Tan, T, Yang, GL, Zang, X, Zhang, J, Wang, Y, Yang, Y, Liu, Y, Zhang, Y, Yang, B, Ma, J & Ma, S 2019, 'The TRIM protein Mitsugumin 53 enhances survival and therapeutic efficacy of stem cells in murine traumatic brain injury', Stem Cell Research and Therapy, vol. 10, no. 1, 352. https://doi.org/10.1186/s13287-019-1433-4
Guan, Fangxia ; Huang, Tuanjie ; Wang, Xinxin ; Xing, Qu ; Gumpper, Kristyn ; Li, Peng ; Song, Jishi ; Tan, Tao ; Yang, Greta Luyuan ; Zang, Xingxing ; Zhang, Jiewen ; Wang, Yuming ; Yang, Yunlei ; Liu, Yashi ; Zhang, Yanting ; Yang, Bo ; Ma, Jianjie ; Ma, Shanshan. / The TRIM protein Mitsugumin 53 enhances survival and therapeutic efficacy of stem cells in murine traumatic brain injury. In: Stem Cell Research and Therapy. 2019 ; Vol. 10, No. 1.
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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.",
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T1 - The TRIM protein Mitsugumin 53 enhances survival and therapeutic efficacy of stem cells in murine traumatic brain injury

AU - Guan, Fangxia

AU - Huang, Tuanjie

AU - Wang, Xinxin

AU - Xing, Qu

AU - Gumpper, Kristyn

AU - Li, Peng

AU - Song, Jishi

AU - Tan, Tao

AU - Yang, Greta Luyuan

AU - Zang, Xingxing

AU - Zhang, Jiewen

AU - Wang, Yuming

AU - Yang, Yunlei

AU - Liu, Yashi

AU - Zhang, Yanting

AU - Yang, Bo

AU - Ma, Jianjie

AU - Ma, Shanshan

PY - 2019/11/28

Y1 - 2019/11/28

N2 - 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.

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 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.

KW - Mitsugumin 53

KW - Neuroprotection

KW - PI3K-Akt-GSK3β

KW - Stem cells

KW - Traumatic brain injury

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