Stoke Mandeville Spinal Research: Four key areas of research
Spinal cord injuries (SCIs) are complex and life-altering, often leading to severe motor and sensory impairments.
Over the years, medical and technological advancements have strived to alleviate the impact of these injuries, including neural regeneration, rehabilitation techniques, neurostimulation and brain-machine interfaces.
The US National Institute of Child Health and Human Development states that “researchers are continually working on new treatments, including prostheses and medications, which may promote regeneration of nerve cells or improve the function of the nerves that remain after a spinal cord injury.”
Worldwide, studies have been undertaken involving stem cell grafting for a number of years, and there has been growing interest in the use of genetically-modified human neural stem cells (hNSCs) as a potential therapy for spinal cord injuries.
It has been reported in Advanced Science that a research team co-led by City University of Hong Kong (CityU) and The University of Hong Kong have generated hNSCs that exhibit what they claim is “enhanced therapeutic potential” in spinal cord injury treatment.
Spinal neurons with long axons play critical roles in transmitting signals between the brain and the rest of the body, controlling movement and sensory perception. Spinal cord injury causes irreversible damage to neurons and axons, which significantly interrupts signal transmission, leading to defective locomotion and somatosensory functions.
Professor Jessica Liu Aijia, Assistant Professor in the Department of Neuroscience at CityU and the co-leader of the research, stated:
"While recent progress has been made in promoting spinal cord regeneration through transplantation of hNSCs derived from human induced pluripotent stem cells, the degree of functional recovery obtained has been modest. This is largely due to the hostile micro-environment around the lesion site, such as the formation of barrier-like structures called astroglial scars and the lack of neurotrophic factors in adults for neuronal differentiation. These factors hinder functional neuronal regeneration, resulting in prolonged repairing and limited functional recovery."
To overcome the adverse effects of the post-injury micro-environment, the joint-research team found that specifically modulating SOX9 expression to approximately 50% in hNSCs can effectively promote the reconstruction of damaged neural circuits and restore locomotor functions.
To examine the evidence in a more clinically relevant model, the researchers generated a rat spinal contusion model. The rats recorded limb stepping ability and coordination and demonstrated a good gait with recovery of paw positions and toe movement.
Professor Liu said: "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...
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 minimizes the risk of rejection by the immune system. It provides a more effective autologous stem cell therapy for severe traumatic spinal cord injury,".
Developments in research in treating SCI are continually evolving. While further research and clinical trials are necessary, genetically modified hNSCs might offer a potential innovative therapeutic avenue for spinal cord injury treatment in the future.
More information: Jessica Aijia Liu 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). DOI: 10.1002/advs.202205804
The Clyde & Co spinal subject matter group keeps track of all relevant news, scientific advancements, and all other developments relevant to SCI patients and claims.