Factors Secreted by Endothelial Progenitor Cells Enhance Neurorepair Responses after Cerebral Ischemia in Mice
Rosell Novel, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Morancho, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Navarro Sobrino, Míriam (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martinez-Saez, Elena (Hospital Universitari Vall d'Hebron)
Hernandez Guillamon, Maria Mar (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Lope-Piedrafita, Silvia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Barceló, Verónica (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Borràs i Serres, Francesc Enric (Hospital Universitari Vall d'Hebron)
Penalba, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
García Bonilla, Lídia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Montaner, Joan (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Data:	2013
Resum:	Cell therapy with endothelial progenitor cells (EPCs) has emerged as a promising strategy to regenerate the brain after stroke. Here, we aimed to investigate if treatment with EPCs or their secreted factors could potentiate angiogenesis and neurogenesis after permanent focal cerebral ischemia in a mouse model of ischemic stroke. BALB/C male mice were subjected to distal occlusion of the middle cerebral artery, and EPCs, cell-free conditioned media (CM) obtained from EPCs, or vehicle media were administered one day after ischemia. Magnetic resonance imaging (MRI) was performed at baseline to confirm that the lesions were similar between groups. Immunohistochemical and histological evaluation of the brain was performed to evaluate angio-neurogenesis and neurological outcome at two weeks. CM contained growth factors, such as VEGF, FGF-b and PDGF-bb. A significant increase in capillary density was noted in the peri-infarct areas of EPC- and CM-treated animals. Bielschowsky's staining revealed a significant increase in axonal rewiring in EPC-treated animals compared with shams, but not in CM-treated mice, in close proximity with DCX-positive migrating neuroblasts. At the functional level, post-ischemia forelimb strength was significantly improved in animals receiving EPCs or CM, but not in those receiving vehicle media. In conclusion, we demonstrate for the first time that the administration of EPC-secreted factors could become a safe and effective cell-free option to be considered in future therapeutic strategies for stroke.
Ajuts:	Ministerio de Ciencia e Innovación CP09/00265
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 8 (september 2013) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0073244
PMID: 24023842

10 p, 3.9 MB

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