Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats
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 und...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9593 |
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| author | Serhiy Forostyak Oksana Forostyak Jessica C. F. Kwok Nataliya Romanyuk Monika Rehorova Jan Kriska Govindan Dayanithi Ruma Raha-Chowdhury Pavla Jendelova Miroslava Anderova James W. Fawcett Eva Sykova |
| author_facet | Serhiy Forostyak Oksana Forostyak Jessica C. F. Kwok Nataliya Romanyuk Monika Rehorova Jan Kriska Govindan Dayanithi Ruma Raha-Chowdhury Pavla Jendelova Miroslava Anderova James W. Fawcett Eva Sykova |
| author_sort | Serhiy Forostyak |
| collection | DOAJ |
| description | 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<sup>G93A</sup> 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<sup>G93A</sup> rats at the terminal stage. NP-iPS application led to normalized host genes expression (<i>versican, has-1, tenascin-R, ngf, igf-1, bdnf, bax, bcl-2, and casp-3</i>) 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). |
| first_indexed | 2024-03-10T14:00:54Z |
| format | Article |
| id | doaj.art-4543d7869b3143b7b39478900ec4034d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:00:54Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4543d7869b3143b7b39478900ec4034d2023-11-21T01:07:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124959310.3390/ijms21249593Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS RatsSerhiy Forostyak0Oksana Forostyak1Jessica C. F. Kwok2Nataliya Romanyuk3Monika Rehorova4Jan Kriska5Govindan Dayanithi6Ruma Raha-Chowdhury7Pavla Jendelova8Miroslava Anderova9James W. Fawcett10Eva Sykova11Institute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicJohn van Geest Centre for Brain Repair (BRC), Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UKInstitute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Experimental Medicine, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicA 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<sup>G93A</sup> 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<sup>G93A</sup> rats at the terminal stage. NP-iPS application led to normalized host genes expression (<i>versican, has-1, tenascin-R, ngf, igf-1, bdnf, bax, bcl-2, and casp-3</i>) 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).https://www.mdpi.com/1422-0067/21/24/9593proteoglycansplasticityneurodegenerationstem cellsiPSALS |
| spellingShingle | Serhiy Forostyak Oksana Forostyak Jessica C. F. Kwok Nataliya Romanyuk Monika Rehorova Jan Kriska Govindan Dayanithi Ruma Raha-Chowdhury Pavla Jendelova Miroslava Anderova James W. Fawcett 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 proteoglycans plasticity neurodegeneration stem cells iPS ALS |
| title | Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats |
| title_full | Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats |
| title_fullStr | Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats |
| title_full_unstemmed | Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats |
| title_short | Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats |
| title_sort | transplantation of neural precursors derived from induced pluripotent cells preserve perineuronal nets and stimulate neural plasticity in als rats |
| topic | proteoglycans plasticity neurodegeneration stem cells iPS ALS |
| url | https://www.mdpi.com/1422-0067/21/24/9593 |
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