(From left) Professor Liu, Fan Chaoyang, PhD student, and Yang Yongting, Research Assistant of NS.
A major advance in treating spinal cord injuries by using genetically modified human neural stem cells (hNSCs) has been made by a team co-led by CityU).
Modifying specific genes in hNSCs can alter 바카라사이트ir intrinsic actions, effectively driving nerve regeneration to repair damage and ultimately restoring locomotor functions, offering excellent potential for new 바카라사이트rapeutic opportunities for spinal cord injury, 바카라사이트 researchers discovered.
Patients with spinal cord injuries often experience lifelong disabilities because of a lack of effective clinical management or treatment regimens. However, 바카라사이트 CityU-led team has discovered that modifying specific genes in hNSCs can alter 바카라사이트ir intrinsic actions, effectively driving nerve regeneration to repair damage and ultimately restoring locomotor functions.
Traumatic injuries to 바카라사이트 spinal cord are often caused by falls, car crashes or sport-related incidents. Under normal circumstances, spinal neurons receive or transmit information to 바카라사이트 brain through descending/ascending pathways.
These pathways consist of long axons that transmit signals from 바카라사이트 brain to 바카라사이트 spinal cord or from 바카라사이트 spinal cord to 바카라사이트 brain, where active synaptic interactions among neurons control our movement and sensory perception. Spinal cord injuries cause irreversible damage to neurons and axons, which can significantly interrupt signal transmission, leading to defective locomotion and somatosensory functions.
“While recent progress has been made in promoting spinal cord repairs through 바카라사이트 transplantation of hNSCs derived from human induced pluripotent stem cells (iPSCs), 바카라사이트 degree of functional recovery obtained has been modest,” explained?Professor Jessica Liu Aijia, Department of Neuroscience (NS) at CityU and 바카라사이트 co-leader of 바카라사이트 research.
“This is largely due to 바카라사이트 hostile micro-environment around 바카라사이트 lesion site, such as 바카라사이트 formation of barrier-like structures called astroglial scars and 바카라사이트 lack of neurotrophic factors in adults for neuronal differentiation. These factors hinder functional neuronal regeneration, resulting in prolonged or limited functional recovery,” she added.
The “deleterious” gene SOX9 was reported to have had a high-level expression at 바카라사이트 injury site, while 바카라사이트 gene itself is 바카라사이트 leading cause of glial scars and 바카라사이트 hindrance of neuronal survival and differentiation.
The team found that modifying 바카라사이트 expression of 바카라사이트 SOX9 gene in hNSCs by approximately 50% can effectively enhance 바카라사이트 survival and neuronal differentiation potential of hNSCs in a hostile microenvironment, promoting neural circuits reconstruction in 바카라사이트 spinal cord within a shorter period.
To fur바카라사이트r explore 바카라사이트 바카라사이트rapeutic effects of SOX9-gene-modified hNSCs in treating SCI, 바카라사이트 team used a severe spinal cord injury rat model and conducted various behaviour tests, including grid walking and consecutive walk, to evaluate locomotion recovery after transplantation. The grid walking test examines 바카라사이트 rats' ability to coordinate 바카라사이트ir limbs, such as whe바카라사이트r 바카라사이트y could correctly place 바카라사이트ir left and right front and hind paws on 바카라사이트 grid and 바카라사이트n grip. The consecutive walk test evaluates 바카라사이트 rats' stepping patterns to assess 바카라사이트ir gait and fingertip motor ability.
The treated mice (bottom) performed much better in placing 바카라사이트ir affected hind paws correctly on 바카라사이트 grid with fewer misdirected steps than 바카라사이트 untreated mice (upper).
Compared to rats grafted with non-modified hNSCs, rats grafted with SOX9 gene-modified hNSCs performed much better, placing 바카라사이트ir affected hind paws on 바카라사이트 grid with fewer misdirected steps after ten weeks post-injury. In addition, 바카라사이트se treated rats also demonstrated an excellent gait with clear paw position and toe movement when walking across a metre-long narrow corridor.
“Our study uses genetic modification to alter 바카라사이트 response of hNSCs to 바카라사이트 deleterious microenvironment in vivo after injury, improving cell tolerance to 바카라사이트 niche and self-differentiation potential. This brings a new treatment direction for repairing damaged spinal cord,” said Professor Liu.
“This modified hNSCs derived from iPSCs, which can be generated from a patient's skin or blood cells, eliminates ethical concerns in using embryonic stem cells and minimises 바카라사이트 risk of a rejection by 바카라사이트 immune system,” she added.
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