Elucidating the Pivotal Neuroimmunomodulation of Stem Cells in Spinal Cord Injury Repair

Abstract

Spinal cord injury (SCI) is a distressing incident with abrupt onset of the motor as well as sensory dysfunction, and most often, the injury occurs as result of high-energy or velocity accidents as well as contact sports and falls in the elderly. The key challenges associated with nerve repair are the lack of self-repair as well as neurotrophic factors and primary and secondary neuronal apoptosis, as well as factors that prevent the regeneration of axons locally. Neurons that survive the initial traumatic damage may be lost due to pathogenic activities like neuroinflammation and apoptosis. Implanted stem cells are capable of differentiating into neural cells that replace injured cells as well as offer local neurotrophic factors that aid neuroprotection, immunomodulation, axonal sprouting, axonal regeneration, and remyelination. At the microenvironment of SCI, stem cells are capable of producing growth factors like brain-derived neurotrophic factor and nerve growth factor which triggers neuronal survival as well as axonal regrowth. Although stem cells have proven to be of therapeutic value in SCI, the major disadvantage of some of the cell types is the risk for tumorigenicity due to the contamination of undifferentiated cells prior to transplantation. Local administration of stem cells via either direct cellular injection into the spinal cord parenchyma or intrathecal administration into the subarachnoid space is currently the best transplantation modality for stem cells during SCI.

Neural Stem Cells Overexpressing Nerve Growth Factor Improve Functional Recovery in Rats Following Spinal Cord Injury via Modulating Microenvironment and Enhancing Endogenous Neurogenesis

“…After SCI, growth factors [e.g., vascular endothelial-derived growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), etc] were reported to have pro-repair impact on the microenvironment for supporting spontaneous neurofunctional recovery ( Richard and Sackey, 2021 ). Thus, we further evaluated the expression of multiple growth factors around the lesion core.…”

Application of extracorporeal shock wave therapy in nervous system diseases: A review

“…Zhang et al ( 110 ) found that ESWT enhanced the proliferation and differentiation of NSCs by Notch, PI3K/AKT, and Wnt/β-catenin Signaling, leading to the repairment of the damaged nerve function in central nervous system diseases. It is known that NSCs play a crucial role in the central and peripheral nervous system, and could replace damaged neural cells ( 111 – 114 ). It is clear that stem cell proliferation induced by ESWT is of great significance in the repair and regeneration of the nervous system.…”

Hydrogel-based treatments for spinal cord injuries

“…Moreover, the presence of an electrical microenvironment favors the growth of neurons and myelination axon regeneration. Therefore, the design of injectable, conductive, ECM hydrogel materials may provide a new treatment modality for traumatic SCI [ 150 ]. For instance, Luo et al developed a native ECM biopolymer-based hydrogel containing polypyrrole that exhibited similar mechanical and conductive properties as native spinal cord tissue; the hydrogels enabled significant motor function recovery in the spinal cord of rats ( Fig.…”