Comparison between xenogeneic and allogeneic adipose mesenchymal stem cells in the treatment of acute cerebral infarct: Proof of concept in rats
Entity
UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)Publisher
BioMed CentralDate
2015-02-01Citation
10.1186/s12967-015-0406-3
Journal of Translational Medicine 13.1 (2015): 1-10
ISSN
1479-5876DOI
10.1186/s12967-015-0406-3Funded by
This research was supported by research grants FIS06/0575, FIS09/01606, FIS12/01754 and INVICTUS (RD12/0014/0006) (Spanish Neurovascular Network), Cellerix, and Research Institute Carlos III, Ministry of Science and Innovation of Spain.Project
Gobierno de España. FIS06/0575; Gobierno de España. FIS09/01606; Gobierno de España. FIS12/01754Editor's Version
http://dx.doi.org/10.1186/s12967-015-0406-3Subjects
Allogeneic and xenogeneic AD-MSCs; Functional recovery; Safety; Stroke; MedicinaRights
© 2015 Gutiérrez-Fernández et al.Abstract
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 × 106), allogeneic rAD-MSCs (2 × 106) 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
Files in this item
Google Scholar:Gutierrez-Fernandez, María
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Rodríguez-Frutos, Berta
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Ramos-Cejudo, Jaime
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Otero-Ortega, Laura
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Fuentes Gimeno, Blanca Eulalia
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Vallejo-Cremades, María Teresa
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Sanz-Cuesta, Enrique E.
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Díez Tejedor, Exuperio
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