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Intravenous delivery of adipose tissue-derived mesenchymal stem cells improves brain repair in hyperglycemic stroke rats

BACKGROUND: Over 50% of acute stroke patients have hyperglycemia, which is associated with a poorer prognosis and outcome. Our aim was to investigate the impact of hyperglycemia on behavioral recovery and brain repair of delivered human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) in a r...

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Autores principales: Gómez-de Frutos, Mari Carmen, Laso-García, Fernando, Diekhorst, Luke, Otero-Ortega, Laura, Fuentes, Blanca, Jolkkonen, Jukka, Detante, Olivier, Moisan, Anaick, Martínez-Arroyo, Arturo, Díez-Tejedor, Exuperio, Gutiérrez-Fernández, María
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637493/
https://www.ncbi.nlm.nih.gov/pubmed/31315686
http://dx.doi.org/10.1186/s13287-019-1322-x
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author Gómez-de Frutos, Mari Carmen
Laso-García, Fernando
Diekhorst, Luke
Otero-Ortega, Laura
Fuentes, Blanca
Jolkkonen, Jukka
Detante, Olivier
Moisan, Anaick
Martínez-Arroyo, Arturo
Díez-Tejedor, Exuperio
Gutiérrez-Fernández, María
author_facet Gómez-de Frutos, Mari Carmen
Laso-García, Fernando
Diekhorst, Luke
Otero-Ortega, Laura
Fuentes, Blanca
Jolkkonen, Jukka
Detante, Olivier
Moisan, Anaick
Martínez-Arroyo, Arturo
Díez-Tejedor, Exuperio
Gutiérrez-Fernández, María
author_sort Gómez-de Frutos, Mari Carmen
collection PubMed
description BACKGROUND: Over 50% of acute stroke patients have hyperglycemia, which is associated with a poorer prognosis and outcome. Our aim was to investigate the impact of hyperglycemia on behavioral recovery and brain repair of delivered human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) in a rat model of permanent middle cerebral artery occlusion (pMCAO). METHODS: Hyperglycemia was induced in rats by the administration of nicotinamide and streptozotocin. The rats were then subjected to stroke by a pMCAO model. At 48 h post-stroke, 1 × 10(6) hAD-MSCs or saline were intravenously administered. We evaluated behavioral outcome, infarct size by MRI, and brain plasticity markers by immunohistochemistry (glial fibrillary acidic protein [GFAP], Iba-1, synaptophysin, doublecortin, CD-31, collagen-IV, and α-smooth muscle actin [α-SMA]). RESULTS: The hyperglycemic group exhibited more severe neurological deficits; lesion size and diffusion coefficient were larger compared with the non-hyperglycemic rats. GFAP, Iba-1, and α-SMA were increased in the hyperglycemic group. The hyperglycemic rats administered hAD-MSCs at 48 h after pMCAO had improved neurological impairment. Although T2-MRI did not show differences in lesion size between groups, the rADC values were lower in the treated group. Finally, the levels of GFAP, Iba-1, and arterial wall thickness were lower in the treated hyperglycemic group than in the nontreated hyperglycemic group at 6 weeks post-stroke. CONCLUSIONS: Our data suggest that rats with hyperglycemic ischemic stroke exhibit increased lesion size and impaired brain repair processes, which lead to impairments in behavioral recovery after pMCAO. More importantly, hAD-MSC administration induced better anatomical tissue preservation, associated with a good behavioral outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-019-1322-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-66374932019-07-25 Intravenous delivery of adipose tissue-derived mesenchymal stem cells improves brain repair in hyperglycemic stroke rats Gómez-de Frutos, Mari Carmen Laso-García, Fernando Diekhorst, Luke Otero-Ortega, Laura Fuentes, Blanca Jolkkonen, Jukka Detante, Olivier Moisan, Anaick Martínez-Arroyo, Arturo Díez-Tejedor, Exuperio Gutiérrez-Fernández, María Stem Cell Res Ther Research BACKGROUND: Over 50% of acute stroke patients have hyperglycemia, which is associated with a poorer prognosis and outcome. Our aim was to investigate the impact of hyperglycemia on behavioral recovery and brain repair of delivered human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) in a rat model of permanent middle cerebral artery occlusion (pMCAO). METHODS: Hyperglycemia was induced in rats by the administration of nicotinamide and streptozotocin. The rats were then subjected to stroke by a pMCAO model. At 48 h post-stroke, 1 × 10(6) hAD-MSCs or saline were intravenously administered. We evaluated behavioral outcome, infarct size by MRI, and brain plasticity markers by immunohistochemistry (glial fibrillary acidic protein [GFAP], Iba-1, synaptophysin, doublecortin, CD-31, collagen-IV, and α-smooth muscle actin [α-SMA]). RESULTS: The hyperglycemic group exhibited more severe neurological deficits; lesion size and diffusion coefficient were larger compared with the non-hyperglycemic rats. GFAP, Iba-1, and α-SMA were increased in the hyperglycemic group. The hyperglycemic rats administered hAD-MSCs at 48 h after pMCAO had improved neurological impairment. Although T2-MRI did not show differences in lesion size between groups, the rADC values were lower in the treated group. Finally, the levels of GFAP, Iba-1, and arterial wall thickness were lower in the treated hyperglycemic group than in the nontreated hyperglycemic group at 6 weeks post-stroke. CONCLUSIONS: Our data suggest that rats with hyperglycemic ischemic stroke exhibit increased lesion size and impaired brain repair processes, which lead to impairments in behavioral recovery after pMCAO. More importantly, hAD-MSC administration induced better anatomical tissue preservation, associated with a good behavioral outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-019-1322-x) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-17 /pmc/articles/PMC6637493/ /pubmed/31315686 http://dx.doi.org/10.1186/s13287-019-1322-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Gómez-de Frutos, Mari Carmen
Laso-García, Fernando
Diekhorst, Luke
Otero-Ortega, Laura
Fuentes, Blanca
Jolkkonen, Jukka
Detante, Olivier
Moisan, Anaick
Martínez-Arroyo, Arturo
Díez-Tejedor, Exuperio
Gutiérrez-Fernández, María
Intravenous delivery of adipose tissue-derived mesenchymal stem cells improves brain repair in hyperglycemic stroke rats
title Intravenous delivery of adipose tissue-derived mesenchymal stem cells improves brain repair in hyperglycemic stroke rats
title_full Intravenous delivery of adipose tissue-derived mesenchymal stem cells improves brain repair in hyperglycemic stroke rats
title_fullStr Intravenous delivery of adipose tissue-derived mesenchymal stem cells improves brain repair in hyperglycemic stroke rats
title_full_unstemmed Intravenous delivery of adipose tissue-derived mesenchymal stem cells improves brain repair in hyperglycemic stroke rats
title_short Intravenous delivery of adipose tissue-derived mesenchymal stem cells improves brain repair in hyperglycemic stroke rats
title_sort intravenous delivery of adipose tissue-derived mesenchymal stem cells improves brain repair in hyperglycemic stroke rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637493/
https://www.ncbi.nlm.nih.gov/pubmed/31315686
http://dx.doi.org/10.1186/s13287-019-1322-x
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