Logo image
Back
Challenges and Efficacy of Astrocyte-to-Neuron Reprogramming in Spinal Cord Injury: In Vitro Insights and In Vivo Outcomes
Preprint   Open access

Challenges and Efficacy of Astrocyte-to-Neuron Reprogramming in Spinal Cord Injury: In Vitro Insights and In Vivo Outcomes

Alessia Niceforo, Lyandysha V Zholudeva, Silvia Fernandes, Michael A Lane and Liang Qiang
bioRxiv : the preprint server for biology
29 Mar 2024
DOI: https://doi.org/10.1101/2024.03.25.586619
PMID: 38585866
url
https://doi.org/10.1101/2024.03.25.586619View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

reprogramming transcription factor neuron astrocyte iPS cells Spinal Cord Injury
Traumatic spinal cord injury (SCI) leads to the disruption of neural pathways, causing loss of neural cells, with subsequent reactive gliosis and tissue scarring that limit endogenous repair. One potential therapeutic strategy to address this is to target reactive scar-forming astrocytes with direct cellular reprogramming to convert them into neurons, by overexpression of neurogenic transcription factors. Here we used lentiviral constructs to overexpress or a combination of microRNAs (miRs) and transfected into cultured and astrocytes experiments revealed cortically-derived astrocytes display a higher efficiency (70%) of reprogramming to neurons than spinal cord-derived astrocytes. In a rat cervical SCI model, the same strategy induced only limited reprogramming of astrocytes. Delivery of reprogramming factors did not significantly affect patterns of breathing under baseline and hypoxic conditions, but significant differences in average diaphragm amplitude were seen in the reprogrammed groups during eupneic breathing, hypoxic, and hypercapnic challenges. These results show that while cellular reprogramming can be readily achieved in carefully controlled conditions, achieving a similar degree of successful reprogramming is challenging and may require additional steps.

Metrics

34 Record Views

Details

Logo image