Gupta S et al. (2023), Regenerative Potential of Injured Spinal Cord i...

XB-ART-60159

Cells 2023 Jun 22;1213:. doi: 10.3390/cells12131694.

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Regenerative Potential of Injured Spinal Cord in the Light of Epigenetic Regulation and Modulation.

Gupta S , Dutta S , Hui SP .

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A spinal cord injury is a form of physical harm imposed on the spinal cord that causes disability and, in many cases, leads to permanent mammalian paralysis, which causes a disastrous global issue. Because of its non-regenerative aspect, restoring the spinal cord's role remains one of the most daunting tasks. By comparison, the remarkable regenerative ability of some regeneration-competent species, such as some Urodeles (Axolotl), Xenopus, and some teleost fishes, enables maximum functional recovery, even after complete spinal cord transection. During the last two decades of intensive research, significant progress has been made in understanding both regenerative cells' origins and the molecular signaling mechanisms underlying the regeneration and reconstruction of damaged spinal cords in regenerating organisms and mammals, respectively. Epigenetic control has gradually moved into the center stage of this research field, which has been helped by comprehensive work demonstrating that DNA methylation, histone modifications, and microRNAs are important for the regeneration of the spinal cord. In this review, we concentrate primarily on providing a comparison of the epigenetic mechanisms in spinal cord injuries between non-regenerating and regenerating species. In addition, we further discuss the epigenetic mediators that underlie the development of a regeneration-permissive environment following injury in regeneration-competent animals and how such mediators may be implicated in optimizing treatment outcomes for spinal cord injurie in higher-order mammals. Finally, we briefly discuss the role of extracellular vesicles (EVs) in the context of spinal cord injury and their potential as targets for therapeutic intervention.

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Species referenced: Xenopus laevis
Genes referenced: fgf20 klf7 rho shh sox11
GO keywords: DNA methylation [+]

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References [+] :

Abematsu, Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury. 2010, Pubmed

	Figure 1. Comparative view of different epigenetic regulations underlying spinal cord regeneration in the axolotl (A) and zebrafish (C) and tail regeneration in Xenopus larvae (B).Red arrows and green arrows indicate downregulation and upregulation of genes and other factors, respectively.
	Figure 2. Comparative view of the Rho-ROCK pathway after SCI in mammals and zebrafish and the role of miR-133b in promoting axon regeneration after SCI in zebrafish through the repression of the Rho-ROCK pathway.
	Figure 3. (A) Repair mechanisms of the nervous system following SCI after the application of EVs. EVs obtained from donor cells exert diverse epigenetic influences within the microenvironment of the injured spinal cord. These effects involve modifications to DNA, histones, and regulation of noncoding RNA, which collectively contribute to the reduction of glial scar formation and enhancement of axonal growth. (B) Strategies for the development of EV-based therapeutics for SCI and evaluation of their regenerative potential. These approaches encompass the design and optimization of EV-based therapies specifically targeted for SCI, including the incorporation of appropriate cargo molecules and modification of EV surface properties. These engineered EVs are then assessed in preclinical SCI models to evaluate their efficacy in promoting CNS-specific regeneration and functional recovery.