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Genetically Modified Neural Stem Cells Show Potential for Spinal Cord Injuries

Imaging of neural stem cells.
Credit: Liu, A. et al, https://doi.org/10.1002/advs.202205804.
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A research team co-led by City University of Hong Kong (CityU) and The University of Hong Kong (HKU) has recently made a significant advancement in spinal cord injury treatment by using genetically modified human neural stem cells (hNSCs). They found that specifically modulating a gene expression to a certain level in hNSCs can effectively promote the reconstruction of damaged neural circuits and restore locomotor functions, offering great potential for new therapeutic opportunities for patients with spinal cord injury.

Traumatic spinal cord injury is a devastating condition that commonly results from accidents such as falls, car crashes or sport-related injuries. Spinal neurons with long axons play critical roles in transmitting signals between the brain and the rest of the body, controlling our movement and sensory perception. Spinal cord injury causes irreversible damage to neurons and axons, which significantly interrupts signal transmission, hence leading to defective locomotion and somatosensory functions.

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A gene – SOX9 was reported with a high-level expression at the injury site in previous studies, and the gene itself is the leading cause of the glial scars’ formation and the hindrance of neuronal survival and differentiation. To overcome the adverse effects of the post-injury micro-environment, the joint-research team engineered the transplanted neural stem cells with a graded reduction of SOX9 by approximately 50%.

To further explore the therapeutic effects of the modified hNSCs in treating spinal cord injury,  the research team used a severe spinal cord injury rat model to evaluate the locomotion recovery after transplantation, including grid walking and consecutive walk. The former recorded limb coordination, such as the capability to grasp a grid rung with correct placement, and the latter recorded stepping patterns to demonstrate their gait and fingertip motor ability.

“Our findings reveal a new treatment direction by using a genetically modified strategy to alter the grafts’ response to the deleterious microenvironment in vivo after injury, improving cell tolerance to the niche and self-differentiation potential. This brings a new treatment direction for repairing damaged spinal cord,” said Professor Liu.

“This genetic modification of hNSCs, particularly those derived from patient-specific human-induced pluripotent stem cells, which can be generated from a patient's skin or blood cells, eliminates ethical concerns in using embryonic stem cells and minimises the risk of rejection by the immune system. It provides a more effective autologous stem cell therapy for severe traumatic spinal cord injury,” she added.

Reference: Liu JA, Tam KW, Chen YL, et al. Transplanting human neural stem cells with ≈50% reduction of SOX9 gene dosage promotes tissue repair and functional recovery from severe spinal cord injury. Advanced Science. 2023;10(20):2205804. doi: 10.1002/advs.202205804

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