In vivo cell fate reprogramming for spinal cord repair

Curr Opin Genet Dev, 2023 · DOI: 10.1016/j.gde.2023.102090 · Published: October 1, 2023

Spinal Cord Injury Regenerative Medicine

Simple Explanation

Spinal cord injury (SCI) often results in the permanent loss of neurons and the disruption of neural circuits, which can lead to behavioral dysfunctions and impose heavy burdens on both caregivers and society. An emerging regeneration-based strategy involves inducing new neurons from resident glia through cell fate reprogramming in vivo. Unlike permanent neuron loss, SCI stimulates proliferation and recruitment of various cell types, including ependymal cells, astrocytes, Nerve/glial antigen 2 (NG2) glia, fibroblasts, microglia, and macrophages, around the injury site

Study Duration

Not specified

Participants

SCI animal models

Evidence Level

Review

Key Findings

1
Biomaterial-elicited neurogenesis from resident NSCs could provide a much-needed therapeutic strategy for patients with severe SCI.
2
Ectopic SOX2 could reprogram NG2 glia into ASCL1+ neural progenitors, which further differentiated into DCX+ immature and neuronal nuclei+ mature neurons.
3
In vivo reprogramming of NG2 glia significantly reduced the glial scar and improved functional recovery after SCI.

Research Summary

Recent evidence suggests that in vivo fate reprogramming of resident cells that are normally non-neurogenic can generate new neurons. This process also improves the pathological microenvironment, and the new neurons can integrate into the local neural network, resulting in better functional outcomes in SCI animal models. In summary, the in vivo reprogramming approach for spinal cord repair is still in its early stages of preclinical investigation, and there are some pitfalls and challenges that require attention.

Practical Implications

Therapeutic Strategy

Biomaterial-elicited neurogenesis from resident NSCs could provide a therapeutic strategy for patients with severe SCI.

Scarring Reduction

In vivo reprogramming of NG2 glia significantly reduced the glial scar and improved functional recovery after SCI, representing a regeneration-based therapeutic strategy.

Clinical Translation

A chemical approach using a NOTCH signaling pathway inhibitor induced neurogenesis near the lesion site, potentially relevant for clinical translation.

Study Limitations

1
Ensuring new neurons are derived from resident glial cells.
2
Generating appropriate neuronal subtypes to improve spinal cord function.
3
Virus-mediated delivery system may face safety issues such as toxicity, tumorigenesis, and mutagenesis.

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