2020
Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats
FOROSTYAK, Serhij; O. FOROSTYAK; J. C. F. KWOK; N. ROMANYUK; Monika REHOROVA et al.Základní údaje
Originální název
Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats
Autoři
FOROSTYAK, Serhij; O. FOROSTYAK; J. C. F. KWOK; N. ROMANYUK; Monika REHOROVA; Jan KRISKA; G. DAYANITHI; R. RAHA-CHOWDHURY; Pavla JENDELOVA; Miroslava ANDEROVA; J. W. FAWCETT a Eva SYKOVA
Vydání
International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2020, 1422-0067
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
10608 Biochemistry and molecular biology
Stát vydavatele
Švýcarsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Označené pro přenos do RIV
Ano
Kód RIV
RIV/00216224:14110/20:00117891
Organizační jednotka
Lékařská fakulta
UT WoS
EID Scopus
Klíčová slova anglicky
proteoglycans; plasticity; neurodegeneration; stem cells; iPS; ALS; motoneuron death; transplantation
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 21. 7. 2021 10:28, Mgr. Tereza Miškechová
Anotace
V originále
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).