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Comparison between xenogeneic and allogeneic adipose mesenchymal stem cells in the treatment of acute cerebral infarct: proof of concept in rats

BACKGROUND: Rat adipose tissue-derived-mesenchymal stem cells (rAD-MSCs) have proven to be safe in experimental animal models of stroke. However, in order to use human AD-MSCs (hAD-MSCs) as a treatment for stroke patients, a proof of concept is needed. We analyzed whether the xenogeneic hAD-MSCs wer...

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Autores principales: Gutiérrez-Fernández, María, Rodríguez-Frutos, Berta, Ramos-Cejudo, Jaime, Otero-Ortega, Laura, Fuentes, Blanca, Vallejo-Cremades, María Teresa, Sanz-Cuesta, Borja Enrique, Díez-Tejedor, Exuperio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322805/
https://www.ncbi.nlm.nih.gov/pubmed/25637958
http://dx.doi.org/10.1186/s12967-015-0406-3
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author Gutiérrez-Fernández, María
Rodríguez-Frutos, Berta
Ramos-Cejudo, Jaime
Otero-Ortega, Laura
Fuentes, Blanca
Vallejo-Cremades, María Teresa
Sanz-Cuesta, Borja Enrique
Díez-Tejedor, Exuperio
author_facet Gutiérrez-Fernández, María
Rodríguez-Frutos, Berta
Ramos-Cejudo, Jaime
Otero-Ortega, Laura
Fuentes, Blanca
Vallejo-Cremades, María Teresa
Sanz-Cuesta, Borja Enrique
Díez-Tejedor, Exuperio
author_sort Gutiérrez-Fernández, María
collection PubMed
description BACKGROUND: Rat adipose tissue-derived-mesenchymal stem cells (rAD-MSCs) have proven to be safe in experimental animal models of stroke. However, in order to use human AD-MSCs (hAD-MSCs) as a treatment for stroke patients, a proof of concept is needed. We analyzed whether the xenogeneic hAD-MSCs were as safe and effective as allogeneic rAD-MSCs in permanent Middle Cerebral Artery Occlusion (pMCAO) in rats. METHODS: Sprague–Dawley rats were randomly divided into three groups, which were intravenously injected with xenogeneic hAD-MSCs (2 × 10(6)), allogeneic rAD-MSCs (2 × 10(6)) or saline (control) at 30 min after pMCAO. Behavior, cell implantation, lesion size and cell death were evaluated. Brain markers such as GFAP (glial fibrillary acid protein), VEGF (vascular endothelial growth factor) and SYP (synaptophysin) and tumor formation were analyzed. RESULTS: Compared to controls, recovery was significantly better at 24 h and continued to be so at 14 d after IV administration of either hAD-MSCs or rAD-MSCs. No reduction in lesion size or migration/implantation of cells in the damaged brain were observed in the treatment groups. Nevertheless, cell death was significantly reduced with respect to the control group in both treatment groups. VEGF and SYP levels were significantly higher, while those of GFAP were lower in the treated groups. At three months, there was no tumor formation. CONCLUSIONS: hAD-MSCs and rAD-MSCs were safe and without side effects or tumor formation. Both treatment groups showed equal efficacy in terms of functional recovery and decreased ischemic brain damage (cell death and glial scarring) and resulted in higher angiogenesis and synaptogenesis marker levels.
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spelling pubmed-43228052015-02-11 Comparison between xenogeneic and allogeneic adipose mesenchymal stem cells in the treatment of acute cerebral infarct: proof of concept in rats Gutiérrez-Fernández, María Rodríguez-Frutos, Berta Ramos-Cejudo, Jaime Otero-Ortega, Laura Fuentes, Blanca Vallejo-Cremades, María Teresa Sanz-Cuesta, Borja Enrique Díez-Tejedor, Exuperio J Transl Med Research BACKGROUND: Rat adipose tissue-derived-mesenchymal stem cells (rAD-MSCs) have proven to be safe in experimental animal models of stroke. However, in order to use human AD-MSCs (hAD-MSCs) as a treatment for stroke patients, a proof of concept is needed. We analyzed whether the xenogeneic hAD-MSCs were as safe and effective as allogeneic rAD-MSCs in permanent Middle Cerebral Artery Occlusion (pMCAO) in rats. METHODS: Sprague–Dawley rats were randomly divided into three groups, which were intravenously injected with xenogeneic hAD-MSCs (2 × 10(6)), allogeneic rAD-MSCs (2 × 10(6)) or saline (control) at 30 min after pMCAO. Behavior, cell implantation, lesion size and cell death were evaluated. Brain markers such as GFAP (glial fibrillary acid protein), VEGF (vascular endothelial growth factor) and SYP (synaptophysin) and tumor formation were analyzed. RESULTS: Compared to controls, recovery was significantly better at 24 h and continued to be so at 14 d after IV administration of either hAD-MSCs or rAD-MSCs. No reduction in lesion size or migration/implantation of cells in the damaged brain were observed in the treatment groups. Nevertheless, cell death was significantly reduced with respect to the control group in both treatment groups. VEGF and SYP levels were significantly higher, while those of GFAP were lower in the treated groups. At three months, there was no tumor formation. CONCLUSIONS: hAD-MSCs and rAD-MSCs were safe and without side effects or tumor formation. Both treatment groups showed equal efficacy in terms of functional recovery and decreased ischemic brain damage (cell death and glial scarring) and resulted in higher angiogenesis and synaptogenesis marker levels. BioMed Central 2015-02-01 /pmc/articles/PMC4322805/ /pubmed/25637958 http://dx.doi.org/10.1186/s12967-015-0406-3 Text en © Gutiérrez-Fernández et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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
Gutiérrez-Fernández, María
Rodríguez-Frutos, Berta
Ramos-Cejudo, Jaime
Otero-Ortega, Laura
Fuentes, Blanca
Vallejo-Cremades, María Teresa
Sanz-Cuesta, Borja Enrique
Díez-Tejedor, Exuperio
Comparison between xenogeneic and allogeneic adipose mesenchymal stem cells in the treatment of acute cerebral infarct: proof of concept in rats
title Comparison between xenogeneic and allogeneic adipose mesenchymal stem cells in the treatment of acute cerebral infarct: proof of concept in rats
title_full Comparison between xenogeneic and allogeneic adipose mesenchymal stem cells in the treatment of acute cerebral infarct: proof of concept in rats
title_fullStr Comparison between xenogeneic and allogeneic adipose mesenchymal stem cells in the treatment of acute cerebral infarct: proof of concept in rats
title_full_unstemmed Comparison between xenogeneic and allogeneic adipose mesenchymal stem cells in the treatment of acute cerebral infarct: proof of concept in rats
title_short Comparison between xenogeneic and allogeneic adipose mesenchymal stem cells in the treatment of acute cerebral infarct: proof of concept in rats
title_sort comparison between xenogeneic and allogeneic adipose mesenchymal stem cells in the treatment of acute cerebral infarct: proof of concept in rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322805/
https://www.ncbi.nlm.nih.gov/pubmed/25637958
http://dx.doi.org/10.1186/s12967-015-0406-3
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