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Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo—Is Immunosuppression Mandatory?

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, causing motor neuron and skeletal muscle loss and death. One of the promising therapeutic approaches is stem cell graft application into the brain; however, an immune reaction against it creates serious limitations. This...

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Autores principales: Kozlowska, Urszula, Klimczak, Aleksandra, Bednarowicz, Karolina Anna, Zalewski, Tomasz, Rozwadowska, Natalia, Chojnacka, Katarzyna, Jurga, Stefan, Barnea, Eytan R., Kurpisz, Maciej K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308088/
https://www.ncbi.nlm.nih.gov/pubmed/34359973
http://dx.doi.org/10.3390/cells10071804
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author Kozlowska, Urszula
Klimczak, Aleksandra
Bednarowicz, Karolina Anna
Zalewski, Tomasz
Rozwadowska, Natalia
Chojnacka, Katarzyna
Jurga, Stefan
Barnea, Eytan R.
Kurpisz, Maciej K.
author_facet Kozlowska, Urszula
Klimczak, Aleksandra
Bednarowicz, Karolina Anna
Zalewski, Tomasz
Rozwadowska, Natalia
Chojnacka, Katarzyna
Jurga, Stefan
Barnea, Eytan R.
Kurpisz, Maciej K.
author_sort Kozlowska, Urszula
collection PubMed
description Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, causing motor neuron and skeletal muscle loss and death. One of the promising therapeutic approaches is stem cell graft application into the brain; however, an immune reaction against it creates serious limitations. This study aimed to research the efficiency of glial restricted progenitors (GRPs) grafted into murine CNS (central nervous system) in healthy models and the SOD1G93A ALS disease model. The cellular grafts were administered in semiallogenic and allogeneic settings. To investigate the models of immune reaction against grafted GRPs, we applied three immunosuppressive/immunomodulatory regimens: preimplantation factor (PiF); Tacrolimus; and CTLA-4, MR1 co-stimulatory blockade. We tracked the cells with bioluminescence imaging (BLI) in vivo to study their survival. The immune response character was evaluated with brain tissue assays and multiplex ELISA in serum and cerebrospinal fluid (CSF). The application of immunosuppressive drugs is disputable when considering cellular transplants into the immune-privileged site/brain. However, our data revealed that semiallogenic GRP graft might survive inside murine CNS without the necessity to apply any immunomodulation or immunosuppression, whereas, in the situation of allogeneic mouse setting, the combination of CTLA-4, MR1 blockade can be considered as the best immunosuppressive option.
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spelling pubmed-83080882021-07-25 Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo—Is Immunosuppression Mandatory? Kozlowska, Urszula Klimczak, Aleksandra Bednarowicz, Karolina Anna Zalewski, Tomasz Rozwadowska, Natalia Chojnacka, Katarzyna Jurga, Stefan Barnea, Eytan R. Kurpisz, Maciej K. Cells Article Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, causing motor neuron and skeletal muscle loss and death. One of the promising therapeutic approaches is stem cell graft application into the brain; however, an immune reaction against it creates serious limitations. This study aimed to research the efficiency of glial restricted progenitors (GRPs) grafted into murine CNS (central nervous system) in healthy models and the SOD1G93A ALS disease model. The cellular grafts were administered in semiallogenic and allogeneic settings. To investigate the models of immune reaction against grafted GRPs, we applied three immunosuppressive/immunomodulatory regimens: preimplantation factor (PiF); Tacrolimus; and CTLA-4, MR1 co-stimulatory blockade. We tracked the cells with bioluminescence imaging (BLI) in vivo to study their survival. The immune response character was evaluated with brain tissue assays and multiplex ELISA in serum and cerebrospinal fluid (CSF). The application of immunosuppressive drugs is disputable when considering cellular transplants into the immune-privileged site/brain. However, our data revealed that semiallogenic GRP graft might survive inside murine CNS without the necessity to apply any immunomodulation or immunosuppression, whereas, in the situation of allogeneic mouse setting, the combination of CTLA-4, MR1 blockade can be considered as the best immunosuppressive option. MDPI 2021-07-16 /pmc/articles/PMC8308088/ /pubmed/34359973 http://dx.doi.org/10.3390/cells10071804 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kozlowska, Urszula
Klimczak, Aleksandra
Bednarowicz, Karolina Anna
Zalewski, Tomasz
Rozwadowska, Natalia
Chojnacka, Katarzyna
Jurga, Stefan
Barnea, Eytan R.
Kurpisz, Maciej K.
Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo—Is Immunosuppression Mandatory?
title Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo—Is Immunosuppression Mandatory?
title_full Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo—Is Immunosuppression Mandatory?
title_fullStr Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo—Is Immunosuppression Mandatory?
title_full_unstemmed Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo—Is Immunosuppression Mandatory?
title_short Assessment of Immunological Potential of Glial Restricted Progenitor Graft In Vivo—Is Immunosuppression Mandatory?
title_sort assessment of immunological potential of glial restricted progenitor graft in vivo—is immunosuppression mandatory?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308088/
https://www.ncbi.nlm.nih.gov/pubmed/34359973
http://dx.doi.org/10.3390/cells10071804
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