Application and prospects of somatic cell reprogramming technology for spinal cord injury treatment

Abstract

Spinal cord injury (SCI) is a serious neurological trauma that is challenging to treat. After SCI, many neurons in the injured area die due to necrosis or apoptosis, and astrocytes, oligodendrocytes, microglia and other non-neuronal cells become dysfunctional, hindering the repair of the injured spinal cord. Corrective surgery and biological, physical and pharmacological therapies are commonly used treatment modalities for SCI; however, no current therapeutic strategies can achieve complete recovery. Somatic cell reprogramming is a promising technology that has gradually become a feasible therapeutic approach for repairing the injured spinal cord. This revolutionary technology can reprogram fibroblasts, astrocytes, NG2 cells and neural progenitor cells into neurons or oligodendrocytes for spinal cord repair. In this review, we provide an overview of the transcription factors, genes, microRNAs (miRNAs), small molecules and combinations of these factors that can mediate somatic cell reprogramming to repair the injured spinal cord. Although many challenges and questions related to this technique remain, we believe that the beneficial effect of somatic cell reprogramming provides new ideas for achieving functional recovery after SCI and a direction for the development of treatments for SCI.

Clinical application prospects and transformation value of dental follicle stem cells in oral and neurological diseases

“…Proinflammatory cells are then activated, releasing abundant inflammatory cytokines, which induce a cascade of secondary injury[ 82 ]. Many neurons, astrocytes, and other neural cells die in the injured area due to necrosis or apoptosis during the secondary injury[ 83 ]. Until now, current clinical strategies have not achieved satisfactory outcomes due to irreversible damage to neural cells.…”

Biomaterial‐Based Gene Delivery to Central Nervous System Cells for the Treatment of Spinal Cord Injury

“…The use of stem cells isolated from different body tissues such as bone marrow, placenta, olfactory tissues, and the CNS itself has seen extensive application for spinal cord repair strategies. [191,192] With the advent of somatic cell reprograming for example, using retroviral transduction of Oct4, Sox2, Klf4, and c-Myc to generate induced pluripotent stem cells (iPSCs) has provided an expandable source of patient-specific progenitor cells for autologous transplantation to the injured cord [193] without the need for immunosuppression. [194] While the interactions of transplanted stem cells with host injured cord are generally beneficial, [195] the results from several clinical trials have reported mixed results.…”

Neuroplasticity and regeneration after spinal cord injury

“…Zarei-Kheirabadi et al. demonstrated more efficient reprogramming with zinc finger protein 521 (Zfp521) in comparison to Sox2, with motor neuron-evoked potentials observed and improvements in motor function [120 , 121] . Neurogenin2 (Ngn2) converted astrocytes specifically into glutamatergic and GABAergic neurons with induced neurons able to respond to inputs from the dorsal root ganglion [122] .…”

“…used CRISPRa to activate expression of Ngn2 and Islet-1 (Isl1) in vitro and in vivo. ROCK inhibitor Y-27632 administration allowed for improved motor neuronal maturation and branching to the sciatic nerves [120 , 125] . dCas9 is a mutant nuclease deactivated form of Cas9 that can be used to either augment or decrease gene expression without disruption of the DNA strands [113] .…”