Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats

Forostyak, Serhiy; Forostyak, Oksana; Kwok, Jessica; Romanyuk, Nataliya; Řehořová, Monika; Kriška, Ján; Dayanithi, Govindan; Raha-Chowdhury, R.; Jendelová, Pavla; Anděrová, Miroslava; Fawcett, James; Syková, Eva

doi:https://dx.doi.org/10.3390/ijms21249593

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Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats

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SYSNO ASEP	0550900
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats
Author(s)	Forostyak, Serhiy (UEM-P)_{RID, ORCID} Forostyak, Oksana (UEM-P) Kwok, Jessica (UEM-P)_{ORCID, RID} Romanyuk, Nataliya (UEM-P)_RID Řehořová, Monika (UEM-P) Kriška, Ján (UEM-P)_{RID, ORCID} Dayanithi, Govindan (UEM-P)_RID Raha-Chowdhury, R. (GB) Jendelová, Pavla (UEM-P)_{RID, ORCID} Anděrová, Miroslava (UEM-P)_{RID, ORCID} Fawcett, James (UEM-P)_ORCID Syková, Eva (UEM-P)_RID
Article number	9593
Source Title	International Journal of Molecular Sciences. - : MDPI Roč. 21, č. 24 (2020)
Number of pages	25 s.
Language	eng - English
Country	CH - Switzerland
Keywords	proteoglycans ; plasticity ; neurodegeneration ; stem cells ; iPS ; ALS
Subject RIV	FH - Neurology
OECD category	Neurosciences (including psychophysiology
R&D Projects	GA19-02046S GA ČR - Czech Science Foundation (CSF)
	EF15_003/0000419 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Method of publishing	Open access
Institutional support	UEM-P - RVO:68378041
UT WOS	000603507100001
EID SCOPUS	85098229897
DOI	10.3390/ijms21249593
Annotation	A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) treatment is stem cell therapy. Neural progenitors derived from induced pluripotent cells (NP-iPS) might rescue or replace dying motoneurons (MNs). However, the mechanisms responsible for the beneficial effect are not fully understood. The aim here was to investigate the mechanism by studying the effect of intraspinally injected NP-iPS into asymptomatic and early symptomatic superoxide dismutase (SOD)1(G93A) transgenic rats. Prior to transplantation, NP-iPS were characterized in vitro for their ability to differentiate into a neuronal phenotype. Motor functions were tested in all animals, and the tissue was analyzed by immunohistochemistry, qPCR, and Western blot. NP-iPS transplantation significantly preserved MNs, slowed disease progression, and extended the survival of all treated animals. The dysregulation of spinal chondroitin sulfate proteoglycans was observed in SOD1(G93A) rats at the terminal stage. NP-iPS application led to normalized host genes expression (versican, has-1, tenascin-R, ngf, igf-1, bdnf, bax, bcl-2, and casp-3) and the protection of perineuronal nets around the preserved MNs. In the host spinal cord, transplanted cells remained as progenitors, many in contact with MNs, but they did not differentiate. The findings suggest that NP-iPS demonstrate neuroprotective properties by regulating local gene expression and regulate plasticity by modulating the central nervous system (CNS) extracellular matrix such as perineuronal nets (PNNs).
Workplace	Institute of Experimental Medicine
Contact	Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218
Year of Publishing	2022
Electronic address	https://www.mdpi.com/1422-0067/21/24/9593

Number of the records: 1