Neuroblast survival depends on mature vascular network formation after mouse stroke: role of endothelial and smooth muscle progenitor cell co‐administration

神经发生 神经母细胞 祖细胞 血管生成 血管平滑肌 内皮祖细胞 神经保护 缺血 细胞生物学 医学 生物 癌症研究 神经科学 干细胞 内科学 平滑肌
作者
Lina R. Nih,Nicolas Deroide,Carole Déan,Dominique Lerouet,Mathieu Soustrat,Bernard Lévy,Jean‐Sébastien Silvestre,Tatyana Merkulova‐Rainon,Marc Pocard,Isabelle Margaill,Nathalie Kubis
出处
期刊:European Journal of Neuroscience [Wiley]
卷期号:35 (8): 1208-1217 被引量:60
标识
DOI:10.1111/j.1460-9568.2012.08041.x
摘要

Abstract Pro‐angiogenic cell‐based therapies constitute an interesting and attractive approach to enhancing post‐stroke neurogenesis and decreasing neurological deficit. However, most new stroke‐induced neurons die during the first few weeks after ischemia, thus impairing total recovery. Although the neovascularization process involves different cell types and various growth factors, most cell therapy protocols are based on the biological effects of single‐cell‐type populations or on the administration of heterogeneous populations of progenitors, namely human cord blood‐derived CD34 + cells, with scarce vascular progenitor cells. Tight cooperation between endothelial cells and smooth muscle cells/pericytes is critical for the development of functional neovessels. We hypothesized that neuroblast survival in stroke brain depends on mature vascular network formation. In this study, we injected a combination of endothelial progenitor cells (EPCs) and smooth muscle progenitor cells (SMPCs), isolated from human umbilical cord blood, into a murine model of permanent focal ischemia induced by middle cerebral artery occlusion. The co‐administration of SMPCs and EPCs induced enhanced angiogenesis and vascular remodeling in the peri‐infarct and infarct areas, where vessels exhibited a more mature phenotype. This activation of vessel growth resulted in the maintenance of neurogenesis and neuroblast migration to the peri‐ischemic cortex. Our data suggest that a mature vascular network is essential for neuroblast survival after cerebral ischemia, and that co‐administration of EPCs and SMPCs may constitute a novel therapeutic strategy for improving the treatment of stroke.

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