Novel innovations in cell and gene therapies for spinal cord injury

Abstract

Spinal cord injury (SCI) leads to chronic and multifaceted disability, which severely impacts the physical and mental health as well as the socio-economic status of affected individuals. Permanent disabilities following SCI result from the failure of injured neurons to regenerate and rebuild functional connections with their original targets. Inhibitory factors present in the SCI microenvironment and the poor intrinsic regenerative capacity of adult spinal cord neurons are obstacles for regeneration and functional recovery. Considerable progress has been made in recent years in developing cell and molecular approaches to enable the regeneration of damaged spinal cord tissue. In this review, we highlight several potent cell-based approaches and genetic manipulation strategies (gene therapy) that are being investigated to reconstruct damaged or lost spinal neural circuits and explore emerging novel combinatorial approaches for enhancing recovery from SCI.

Stem Cell Neurodevelopmental Solutions for Restorative Treatments of the Human Trunk and Spine

“…Since the CRISPR/Cas9 system was adapted to mammalian cell types in 2013 (Cong et al, 2013 ), there has been an explosion in the ability to edit genomes to developmental and therapeutic ends including for the CNS (Zavvarian et al, 2020 ). The application of CRISPR and other genetic and optogenetic approaches for SCI treatment was recently expertly reviewed (Paschon et al, 2020 ).…”

Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases

“…Stem cell gene therapy approach NTFs such as BDNF transfects recombinant mesenchymal stem cells delivered by lentiviral vectors can promote recovery and regeneration of neurological function [225] HSP27 delivery HSP27 delivery with a suitable viral vector could reduce the lesion size in experimental stroke model post stroke [226] SOD-HSV-1 Antioxidant gene, SOD when administered through striatal region prior or post cerebral ischemia could improve 50% of neuronal survival due to neuroprotective property [227] RNAi therapy Endothelial gene silencing via T cell invasion could hold the production of neurotoxic cytokine as well as secretion of IF-γ thereby reducing neuroinflammation after ischemia as well as the infarct volume [228] CRISPR/Cas9 genome editing Extenuated the adverse effects caused by spinal cord injury [229] Enhancement of pro-regenerative factors Kruppel-like factors (KLFs) and SOX11 promotes axonal regeneration and neurogenesis [229] Short-hairpin RNA (shRNA) silencing inhibitory factors…”

“…Phosphatase and tensin homolog (PTEN) via mTOR downregulation can reduce damaged neuron regeneration [229] Chloride potassium symporter 5 (KCC2) KCC2 was identified which could maintain a balance in excitatory and inhibitory neurotransmission ratio via modulation of neural circuits and AAV mediated overexpression of KCC2 could improve the functional recovery with less or no adverse effects by influencing synapsin promoter [229] Enzymatic degradation of glial scars secretions…”

Therapeutic Potential of Niche-Specific Mesenchymal Stromal Cells for Spinal Cord Injury Repair

“…There are numerous strategies currently reported for the treatment of SCI; however, stem cell transplantation has gained the most interest [ 4 , 5 ]. The transplantation of autologous or allogeneic cells, including differentiated glia and various stem cells, have been extensively explored [ 6 , 7 , 8 , 9 , 10 ].…”