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In this study, we describe a novel method for isolating BMSC that infiltrate postischemic brain tissue and use this method to identify the genes that are persistently activated or depressed in BMSC that infiltrate brain tissue following ischemic stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods-<\/jats:title><jats:p>Ischemic strokes were induced in C57BL\/6 mice by middle cerebral artery occlusion for 1 h, followed by reperfusion. BMSC were isolated from H-2 Kb-tsA58 (immortomouse\u2122) mice, and were administered (i.v.) 24 h after reperfusion. At the peak of therapeutic improvement (14 days after the ischemic insult), infarcted brain tissue was isolated, and the BMSC were isolated by culturing at 33\u00b0C. Microarray analysis and RT-PCR were performed to compare differential gene expression between na\u00efve and infiltrating BMSC populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results-<\/jats:title><jats:p>Z-scoring revealed dramatic differences in the expression of extracellular genes between na\u00efve and infiltrating BMSC. Pair-wise analysis detected 80 extracellular factor genes that were up-regulated (\u2265 2 fold,<jats:italic>P<\/jats:italic>&lt; 0.05, Benjamini-Hochberg correction) between na\u00efve and infiltrated BMSC. Although several anticipated neuroregenerative, nerve guidance and angiogenic factor (e.g., bFGF, bone morphogenetic protein, angiopoietins, neural growth factor) genes exhibited an increased expression, a remarkable induction of genes for nerve guidance survival (e.g., cytokine receptor-like factor 1, glypican 1, Dickkopf homolog 2, osteopontin) was also noted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions-<\/jats:title><jats:p>BMSC infiltrating the post-ischemic brain exhibit persistent epigenetic changes in gene expression for numerous extracellular genes, compared to their na\u00efve counterparts. These genes are relevant to the neuroprotection, regeneration and angiogenesis previously described following stem cell therapy in animal models of ischemic stroke.<\/jats:p><\/jats:sec>","DOI":"10.1186\/2040-7378-2-11","type":"journal-article","created":{"date-parts":[[2010,5,29]],"date-time":"2010-05-29T06:13:45Z","timestamp":1275113625000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Induction of neuro-protective\/regenerative genes in stem cells infiltrating post-ischemic brain tissue"],"prefix":"10.1186","volume":"2","author":[{"given":"Gokhan","family":"Yilmaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Steven","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cigdem","family":"Erkuran Yilmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D Neil","family":"Granger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,5,28]]},"reference":[{"key":"19_CR1","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/S1474-4422(02)00040-6","volume":"1","author":"M Chopp","year":"2002","unstructured":"Chopp M, Li Y: Treatment of neural injury with marrow stromal cells. 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