White matter injury restoration after stem cell administration in subcortical ischemic stroke
Entity
UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ); Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)Publisher
BioMed CentralDate
2015-06-19Citation
10.1186/s13287-015-0111-4
Stem Cell Research and Therapy 6.1 (2015): 121
ISSN
1757-6512DOI
10.1186/s13287-015-0111-4Funded by
This study was supported by research grants PS12/01754, PI11/00909 and INVICTUS (RD12/0014) (Spanish Neurovascular Network), SAF2010-37926, ProteoRed-PT13/0001/0017 and a Sara Borrell postdoctoral fellowship (CD12/00706, to LOO) from Research Institute Carlos III, Ministry of Science and Innovation of Spain. We greatly appreciate advice from Prof. Avendaño and Dr Negredo and we thank ServingMed.com for linguistic assistance. Furthermore, TS (CP12/03121) and FC (CP14/00154) are recipients of a research contract from Miguel Servet Program of Instituto de Salud Carlos IIIProject
Gobierno de España. SAF2010-37926Editor's Version
http://dx.doi.org/10.1186/s13287-015-0111-4Subjects
White matter; Mesenchymal stem cell; Axonal sprouting; MedicinaRights
© 2015 Otero-Ortega et al.Abstract
Introduction: Despite its high incidence, nerve fiber (axon and myelin) damage after cerebral infarct has not yet
been extensively investigated. The aim of this study was to investigate white matter repair after adipose-derived
mesenchymal stem cell (ADMSC) administration in an experimental model of subcortical stroke. Furthermore, we
aimed to analyze the ADMSC secretome and whether this could be implicated in this repair function.
Methods: An animal model of subcortical ischemic stroke with white matter affectation was induced in rats by
injection of endothelin-1. At 24 hours, 2 × 106 ADMSC were administered intravenously to the treatment group.
Functional evaluation, lesion size, fiber tract integrity, cell death, proliferation, white matter repair markers (Olig-2,
NF, and MBP) and NogoA were all studied after sacrifice (7 days and 28 days). ADMSC migration and implantation
in the brain as well as proteomics analysis and functions of the secretome were also analyzed.
Results: Neither ADMSC migration nor implantation to the brain was observed after ADMSC administration. In
contrast, ADMSC implantation was detected in peripheral organs. The treatment group showed a smaller functional
deficit, smaller lesion area, less cell death, more oligodendrocyte proliferation, more white matter connectivity and
higher amounts of myelin formation. The treated animals also showed higher levels of white matter-associated
markers in the injured area than the control group. Proteomics analysis of the ADMSC secretome identified 2,416
proteins, not all of them previously described to be involved in brain plasticity.
Conclusions: White matter integrity in subcortical stroke is in part restored by ADMSC treatment; this is mediated
by repair molecular factors implicated in axonal sprouting, remyelination and oligodendrogenesis. These findings
are associated with improved functional recovery after stroke
Files in this item
Google Scholar:Otero-Ortega, Laura
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Gutiérrez-Fernández, María
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Ramos-Cejudo, Jaime
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Rodríguez-Frutos, Berta
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Fuentes Gimeno, Blanca Eulalia
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Sobrino, Tomás
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Navarro Hernanz, Teresa
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Campos, Francisco
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López, Juan Antonio
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Cerdán, Sebastián
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Vázquez, Jesús
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Díez Tejedor, Exuperio
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