J 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 (203 Česká republika, garant, domácí), O. FOROSTYAK, J. C. F. KWOK, N. ROMANYUK, Monika REHOROVA (203 Česká republika), Jan KRISKA (203 Česká republika), G. DAYANITHI, R. RAHA-CHOWDHURY, Pavla JENDELOVA (203 Česká republika), Miroslava ANDEROVA (203 Česká republika), J. W. FAWCETT a Eva SYKOVA (203 Česká republika)

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

Impakt faktor

Impact factor: 5.923

Kód RIV

RIV/00216224:14110/20:00117891

Organizační jednotka

Lékařská fakulta

UT WoS

000603507100001

Klíčová slova anglicky

proteoglycans; plasticity; neurodegeneration; stem cells; iPS; ALS; motoneuron death; transplantation

Štítky

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).