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Maryland School of Medicine’s (UMSOM) researchers have found an advancement in stem cell therapy to regenerate neural cells in the brain after cardiac arrest in an animal model. Xiaofeng Jia, BM, MS, PhD, FCCM, a professor of neurosurgery, led the study that discovered some uses of modified sugar molecules on human neural stem cells to improve the prospect that the cure will be effective. The brain’s vital connections were mended thanks to the use of these sugar molecules, which allowed stem cells to multiply and differentiate into neurons more successfully. These discoveries may ultimately result in a better prognosis for individuals suffering from brain damage brought on by cardiac arrest.

The essential study was funded by the National Institute of Neurological Disorders and Stroke (R01NS125232, R01NS110387) and featured in the April Vol. 34 No. 17 front cover of Advanced Functional Materials Journal.

The most common consequence of cardiac arrest is a brain injury, because of the impaired blood flow and oxygen to the brain. About 70 percent of the nearly 7 million people who suffer from cardiac arrest each year experience a robust brain injury that leads to permanent disability.

Due to the harsh in vivo microenvironment of the brain and the consequences at the site of injuries resulting from poor stem cell retention and integration, the use of stem cell therapy to treat neurological dysfunction has long been associated with difficulties.

The capacity of a modified sugar molecule known as the TProp sugar analog to support stem cell viability in the brain has been investigated by researchers at UMSOM thanks to recent advancements in the manipulation and alteration of a cell’s complex carbohydrate structure through metabolic glycoengineering.

The effectiveness of “naive” human neural stem cells and neural stem cells treated with the “TProp” sugar analog were examined in a rat model in this study. The research found that stem cells pretreated with TProp significantly enhanced brain function and minimized anxiety and depression-associated behaviors through various behavioral tests.

Important aspects of cell function are regulated by the Wnt/β-catenin signaling pathway, which is also activated by the treatment. The nerve cells known as neurons—which transmit and receive signals from the brain via the upregulated pathway—are made easier to differentiate from stem cells when TProp is applied.

Synaptic plasticity—the capacity of neurons to change the strength of their connections—and decreased neuroinflammation in the central nervous system were demonstrated by the TProp-pretreated group, providing an increased capacity for brain regeneration and recovery from impaired brain functions.

The outcomes show that glycoengineered stem cells have the potential to promote the growth of new bonds among surviving or regenerated neurons, leading to regenerated circuits in the brain.

“This innovative research has been an important proof of concept study suggesting that stem cells could be used to regenerate neural connections in the brain of patients who suffer a devasting injury after cardiac arrest”, said Dean Mark T. Gladwin, MD, who is the John Z. and Akiko K. Bowers Distinguished Professor and Dean, UMSON, and Vice President for Medical Affairs, University of Maryland, Baltimore. “ Next steps for this translation application include determining the optimal delivery route and timing of metabolically glycoengineered stem cell therapy, as well as systemic evaluation on large animals before this can move into clinical studies.”

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