Improving Efficiency of Direct Pro-Neural Reprogramming: Much-Needed Aid for Neuroregeneration in Spinal Cord Injury
Author:
Chudakova Daria A.1ORCID, Samoilova Ekaterina M.23, Chekhonin Vladimir P.4, Baklaushev Vladimir P.1234ORCID
Affiliation:
1. Federal Center for Brain and Neurotechnologies, Federal Medical and Biological Agency of Russia, 117513 Moscow, Russia 2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia 3. Federal Research and Clinical Center of Specialised Medical Care and Medical Technologies FMBA of Russia, 115682 Moscow, Russia 4. Department of Medical Nanobiotechnology of Medical and Biological Faculty, Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, 117997 Moscow, Russia
Abstract
Spinal cord injury (SCI) is a medical condition affecting ~2.5–4 million people worldwide. The conventional therapy for SCI fails to restore the lost spinal cord functions; thus, novel therapies are needed. Recent breakthroughs in stem cell biology and cell reprogramming revolutionized the field. Of them, the use of neural progenitor cells (NPCs) directly reprogrammed from non-neuronal somatic cells without transitioning through a pluripotent state is a particularly attractive strategy. This allows to “scale up” NPCs in vitro and, via their transplantation to the lesion area, partially compensate for the limited regenerative plasticity of the adult spinal cord in humans. As recently demonstrated in non-human primates, implanted NPCs contribute to the functional improvement of the spinal cord after injury, and works in other animal models of SCI also confirm their therapeutic value. However, direct reprogramming still remains a challenge in many aspects; one of them is low efficiency, which prevents it from finding its place in clinics yet. In this review, we describe new insights that recent works brought to the field, such as novel targets (mitochondria, nucleoli, G-quadruplexes, and others), tools, and approaches (mechanotransduction and electrical stimulation) for direct pro-neural reprogramming, including potential ones yet to be tested.
Funder
State Assignment of the Federal Medical and Biological Agency
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