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Spatiotemporal evolution of early innate immune responses triggered by neural stem cell grafting

INTRODUCTION: Transplantation of neural stem cells (NSCs) is increasingly suggested to become part of future therapeutic approaches to improve functional outcome of various central nervous system disorders. However, recently it has become clear that only a small fraction of grafted NSCs display long...

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Autores principales: Reekmans, Kristien, De Vocht, Nathalie, Praet, Jelle, Fransen, Erik, Le Blon, Debbie, Hoornaert, Chloé, Daans, Jasmijn, Goossens, Herman, Van der Linden, Annemie, Berneman, Zwi, Ponsaerts, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580486/
https://www.ncbi.nlm.nih.gov/pubmed/23241452
http://dx.doi.org/10.1186/scrt147
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author Reekmans, Kristien
De Vocht, Nathalie
Praet, Jelle
Fransen, Erik
Le Blon, Debbie
Hoornaert, Chloé
Daans, Jasmijn
Goossens, Herman
Van der Linden, Annemie
Berneman, Zwi
Ponsaerts, Peter
author_facet Reekmans, Kristien
De Vocht, Nathalie
Praet, Jelle
Fransen, Erik
Le Blon, Debbie
Hoornaert, Chloé
Daans, Jasmijn
Goossens, Herman
Van der Linden, Annemie
Berneman, Zwi
Ponsaerts, Peter
author_sort Reekmans, Kristien
collection PubMed
description INTRODUCTION: Transplantation of neural stem cells (NSCs) is increasingly suggested to become part of future therapeutic approaches to improve functional outcome of various central nervous system disorders. However, recently it has become clear that only a small fraction of grafted NSCs display long-term survival in the (injured) adult mouse brain. Given the clinical invasiveness of NSC grafting into brain tissue, profound characterisation and understanding of early post-transplantation events is imperative to claim safety and efficacy of cell-based interventions. METHODS: Here, we applied in vivo bioluminescence imaging (BLI) and post-mortem quantitative histological analysis to determine the localisation and survival of grafted NSCs at early time points post-transplantation. RESULTS: An initial dramatic cell loss (up to 80% of grafted cells) due to apoptosis could be observed within the first 24 hours post-implantation, coinciding with a highly hypoxic NSC graft environment. Subsequently, strong spatiotemporal microglial and astroglial cell responses were initiated, which stabilised by day 5 post-implantation and remained present during the whole observation period. Moreover, the increase in astrocyte density was associated with a high degree of astroglial scarring within and surrounding the graft site. During the two-week follow up in this study, the NSC graft site underwent extensive remodelling with NSC graft survival further declining to around 1% of the initial number of grafted cells. CONCLUSIONS: The present study quantitatively describes the early post-transplantation events following NSC grafting in the adult mouse brain and warrants that such intervention is directly associated with a high degree of cell loss, subsequently followed by strong glial cell responses.
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spelling pubmed-35804862013-02-26 Spatiotemporal evolution of early innate immune responses triggered by neural stem cell grafting Reekmans, Kristien De Vocht, Nathalie Praet, Jelle Fransen, Erik Le Blon, Debbie Hoornaert, Chloé Daans, Jasmijn Goossens, Herman Van der Linden, Annemie Berneman, Zwi Ponsaerts, Peter Stem Cell Res Ther Research INTRODUCTION: Transplantation of neural stem cells (NSCs) is increasingly suggested to become part of future therapeutic approaches to improve functional outcome of various central nervous system disorders. However, recently it has become clear that only a small fraction of grafted NSCs display long-term survival in the (injured) adult mouse brain. Given the clinical invasiveness of NSC grafting into brain tissue, profound characterisation and understanding of early post-transplantation events is imperative to claim safety and efficacy of cell-based interventions. METHODS: Here, we applied in vivo bioluminescence imaging (BLI) and post-mortem quantitative histological analysis to determine the localisation and survival of grafted NSCs at early time points post-transplantation. RESULTS: An initial dramatic cell loss (up to 80% of grafted cells) due to apoptosis could be observed within the first 24 hours post-implantation, coinciding with a highly hypoxic NSC graft environment. Subsequently, strong spatiotemporal microglial and astroglial cell responses were initiated, which stabilised by day 5 post-implantation and remained present during the whole observation period. Moreover, the increase in astrocyte density was associated with a high degree of astroglial scarring within and surrounding the graft site. During the two-week follow up in this study, the NSC graft site underwent extensive remodelling with NSC graft survival further declining to around 1% of the initial number of grafted cells. CONCLUSIONS: The present study quantitatively describes the early post-transplantation events following NSC grafting in the adult mouse brain and warrants that such intervention is directly associated with a high degree of cell loss, subsequently followed by strong glial cell responses. BioMed Central 2012-12-14 /pmc/articles/PMC3580486/ /pubmed/23241452 http://dx.doi.org/10.1186/scrt147 Text en Copyright ©2012 Reekmans et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Reekmans, Kristien
De Vocht, Nathalie
Praet, Jelle
Fransen, Erik
Le Blon, Debbie
Hoornaert, Chloé
Daans, Jasmijn
Goossens, Herman
Van der Linden, Annemie
Berneman, Zwi
Ponsaerts, Peter
Spatiotemporal evolution of early innate immune responses triggered by neural stem cell grafting
title Spatiotemporal evolution of early innate immune responses triggered by neural stem cell grafting
title_full Spatiotemporal evolution of early innate immune responses triggered by neural stem cell grafting
title_fullStr Spatiotemporal evolution of early innate immune responses triggered by neural stem cell grafting
title_full_unstemmed Spatiotemporal evolution of early innate immune responses triggered by neural stem cell grafting
title_short Spatiotemporal evolution of early innate immune responses triggered by neural stem cell grafting
title_sort spatiotemporal evolution of early innate immune responses triggered by neural stem cell grafting
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580486/
https://www.ncbi.nlm.nih.gov/pubmed/23241452
http://dx.doi.org/10.1186/scrt147
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