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Directed glial differentiation and transdifferentiation for neural tissue regeneration.

Exp Neurol. 2019 Sep;319:112813. doi: 10.1016/j.expneurol.2018.08.010. Epub 2018 Aug 30.

Janowska J1, Gargas J1, Ziemka-Nalecz M1, Zalewska T1, Buzanska L2, Sypecka J3.

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1 Mossakowski Medical Research Centre, Polish Academy of Sciences, NeuroRepair Department, 5, Pawinskiego str., 02-106 Warsaw, Poland.

2 Mossakowski Medical Research Centre, Polish Academy of Sciences, Stem Cell Bioengineering Unit, 5, Pawinskiego str., 02-106 Warsaw, Poland.

3 Mossakowski Medical Research Centre, Polish Academy of Sciences, NeuroRepair Department, 5, Pawinskiego str., 02-106 Warsaw, Poland. Electronic address: This email address is being protected from spambots. You need JavaScript enabled to view it..

Abstract

Glial cells which are indispensable for the central nervous system development and functioning, are proven to be vulnerable to a harmful influence of pathological cues and tissue misbalance. However, they are also highly sensitive to both in vitro and in vivo modulation of their commitment, differentiation, activity and even the fate-switch by different types of bioactive molecules. Since glial cells (comprising macroglia and microglia) are an abundant and heterogeneous population of neural cells, which are almost uniformly distributed in the brain and the spinal cord parenchyma, they all create a natural endogenous reservoir of cells for potential neurogenerative processes required to be initiated in response to pathophysiological cues present in the local tissue microenvironment. The past decade of intensive investigation on a spontaneous and enforced conversion of glial fate into either alternative glial (for instance from oligodendrocytes to astrocytes) or neuronal phenotypes, has considerably extended our appreciation of glial involvement in restoring the nervous tissue cytoarchitecture and its proper functions. The most effective modulators of reprogramming processes have been identified and tested in a series of pre-clinical experiments. A list of bioactive compounds which are potent in guiding in vivo cell fate conversion and driving cell differentiation includes a selection of transcription factors, microRNAs, small molecules, exosomes, morphogens and trophic factors, which are helpful in boosting the enforced neuro-or gliogenesis and promoting the subsequent cell maturation into desired phenotypes. Herein, an issue of their utility for a directed glial differentiation and transdifferentiation is discussed in the context of elaborating future therapeutic options aimed at restoring the diseased nervous tissue.

KEYWORDS:

Cell fate conversion; Glial cell reprogramming; Neural development transdifferentiation; Neurorepair; Pre-clinical studies; Therapeutic strategies; Tissue restoration

 

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