Boosting Stem Cell Therapy by Metabolic Glycoengineering to Improve Outcomes After Cardiac Arrest
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Neuroscience, Cardiovascular, Transplant, 2022
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INTRODUCTION/HYPOTHESIS: Ischemic brain injury after cardiac arrest (CA) causes irreversible neurological dysfunction in over 90% of CA survivors. Current medical treatments do not effectively combat neuronal loss. Evolving neural stem cell (NSC) therapy has shown promising results on neuronal recovery. We previously reported the therapeutic effects of hNSC therapy when compared to the CA-only group. However, the low survival rate of transplanted NSCs hinders further development of the treatment. Metabolic glycoengineering (MGE) is a technique that employed sugar analogs to introduce functional groups to hNSC surface proteins to enhance cell adhesion, and, consequently, survival rates. This project evaluates the impact of MGE on hNSC therapy. METHODS: We developed the novel Ac5ManNTProp analog and optimized the treatment conditions and differentiation ability with hNSCs in vitro. 10 Wistar rats were randomly assigned hNSC and MGE-hNSCs groups (N = 5). After 7 minutes of asphyxial CA, hNSCs were administered intranasally 3 hours after CA. Neurological deficit scores (NDS) were assessed at 24, 48, 72h, and weekly after resuscitation. Open-Field, Elevated Maze, and Tail Suspension tests were performed weekly to monitor behavioral progression, and cell migration was quantified using immunohistochemistry of brain tissues. RESULTS: Ac5ManNTProp overcome the requirement for a complementary scaffold with increased potency and promoted neural differentiation in hNSCs in vitro. Compared to the hNSC group, animals in the MGE-hNSCs group had a significant improvement in neurological function by NDS, with improved grooming activity at 7 days from the Open-Field test, increased time spent in open arms at 14 days from the Elevated Maze test, and enhanced mobility at 28 days from tail Suspension test (all P < 0.05). The MGE technique improved the survival, distribution, and differentiation of transplanted hNSCs, with more neuronal survival in the hippocampus. CONCLUSIONS: Integration of novel MGE to NSC therapy significantly enhances stem cell therapy, improves neurological functional outcomes and long-term behavioral recovery, including decreased anxiety and reduced depression-related behavior. Supported in part by the NINDS R01NS110387 and NHLBI R01HL118084 (both to X Jia).
Meta Tag
Content Type Presentation
Knowledge Area Neuroscience
Knowledge Area Cardiovascular
Knowledge Area Transplant
Knowledge Level Advanced
Learning Pathway Cardiothoracic Critical Care
Membership Level Select
Tag Cerebral Ischemia
Tag Cardiac Arrest
Tag Stem Cells
Tag Biotechnology
Tag Brain Death
Tag Cardiothoracic Critical Care
Year 2022
stem cell therapy
neural injury
metabolic glycoengineering
neurological functional outcomes


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