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.

Basic information

Original name

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

Authors

FOROSTYAK, Serhij (203 Czech Republic, guarantor, belonging to the institution), O. FOROSTYAK, J. C. F. KWOK, N. ROMANYUK, Monika REHOROVA (203 Czech Republic), Jan KRISKA (203 Czech Republic), G. DAYANITHI, R. RAHA-CHOWDHURY, Pavla JENDELOVA (203 Czech Republic), Miroslava ANDEROVA (203 Czech Republic), J. W. FAWCETT and Eva SYKOVA (203 Czech Republic)

Edition

International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2020, 1422-0067

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.923

RIV identification code

RIV/00216224:14110/20:00117891

Organization unit

Faculty of Medicine

DOI

UT WoS

000603507100001

Keywords in English

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

Tags

Tags

International impact, Reviewed
Změněno: 21/7/2021 10:28, Mgr. Tereza Miškechová

Abstract

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).