Bone marrow stromal cells isolated from the infarcted region of the postischemic brain secrete neuroprotective and angiogenic factors

Abstract

Although the therapeutic potential of bone marrow stromal cells (BMSC) has been demonstrated in stroke, there is limited information about the neuroprotective factors secreted by BMSC in the infarcted brain. The objective of this study was to compare the expression of genes for extracellular (EXC) factors produced by BMSC infiltrating brain tissue vs their naïve counterparts. Ischemic stroke was induced in C57BL/6 mice by middle cerebral artery occlusion for 1 h, followed by 24 h reperfusion. BMSC were isolated from H‐2Kb‐tsA58 mice (cells can grow at 33°C), and were administered (i.v.) at 24 h of reperfusion. Infarcted hemispheres were cultured at 33°C for BMSC isolation. Microarray analysis and RT‐PCR were performed to compare gene expression patterns between the BMSC populations in 9 mice. Z‐scoring revealed a robust change in the extracellular region of analyzed cells. Pair‐wise analysis detected 163 extracellular factor genes that were upregulated (≥ 2 fold, P<0.05) between naïve and infiltrated BMSC. Fibroblast growth factors, bone morphogenetic protein, angiopoietins, neural and vascular growth factors were among the expressed genes detected. Our findings indicate that extracellular factors secreted by BMSC infiltrating the postischemic brain may explain the beneficial therapeutic effects of stem cell treatment and reveal potential therapeutic agents for treatment of ischemic stroke. (HL26411)