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 and Eva SYKOVA. Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats. International Journal of Molecular Sciences. Basel: Multidisciplinary Digital Publishing Institute, 2020, vol. 21, No 24, p. 1-25. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms21249593.
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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
Original language English
Type of outcome Article in a journal
Field of Study 10608 Biochemistry and molecular biology
Country of publisher Switzerland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 5.923
RIV identification code RIV/00216224:14110/20:00117891
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.3390/ijms21249593
UT WoS 000603507100001
Keywords in English proteoglycans; plasticity; neurodegeneration; stem cells; iPS; ALS; motoneuron death; transplantation
Tags 14110229, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 21/7/2021 10:28.
Abstract
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).
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