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

0550900 - ÚEM 2022 RIV CH eng J - Článek v odborném periodiku
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
Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats.
International Journal of Molecular Sciences. Roč. 21, č. 24 (2020), č. článku 9593. E-ISSN 1422-0067
Grant CEP: GA ČR(CZ) GA19-02046S; GA MŠMT(CZ) EF15_003/0000419
Institucionální podpora: RVO:68378041
Klíčová slova: proteoglycans * plasticity * neurodegeneration * stem cells * iPS * ALS
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 5.924, rok: 2020
Způsob publikování: Open access
https://www.mdpi.com/1422-0067/21/24/9593

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).
Trvalý link: http://hdl.handle.net/11104/0326819