Abstract
BackgroundTraumatic 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.MethodsIn 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.ResultsWe 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.ConclusionMG53 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.
Highlights
Traumatic brain injury (TBI) is a common neural trauma that often initiates from an external force followed by a secondary neural injury, causing severe physical, psychological, and cognitive impairments [1, 2]
Our results showed that Recombinant human MG53 (rhMG53) and hUC-Mesenchymal stem cells (MSCs) boosted neurogenesis, with more glial fibrillary acidic protein (GFAP)+, DCX+, and neuronal nuclei (NeuN)+ cells presented in the hippocampus at different stages
This study demonstrates that the cotreatment of rhMG53 and hUC-MCSs increases survival signaling in the TBI model, further studies are needed to assess the cellular mechanism that underlies reduced apoptosis, such as whether MG53 has an impact on the mitochondrial welfare of injured neurons under conditions of oxidative stress
Summary
Traumatic brain injury (TBI) is a common neural trauma that often initiates from an external force followed by a secondary neural injury, causing severe physical, psychological, and cognitive impairments [1, 2]. MG53 interacts with p85 as well as CaV3 and activates the pro-survival RISK pathway (including PI3K/Akt/GSK3β cascade and ERK1/2 pathway) to protect ischemic brain injury and myocardial damage [15, 20, 22]. It is unknown whether rhMG53 can enhance the viability and neural repair of hUC-MSCs in TBI and the mechanism remains unclear. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold promise in the treatment of TBI Their efficacy is modest due to low survival and differentiation under the harsh microenvironment of the injured brain. The present study aims to test whether MG53 preserves hUC-MSCs against oxidative stress and enhances stem cell survival and efficacy in TBI treatment
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