(The FASEB Journal. 2008;22:lb97)
© 2008 FASEB
Analysis of extracellular factors secreted by bone marrow stromal cells residing in the infarcted region of the brain after ischemic stroke
Gokhan Yilmaz,
Cigdem Erkuran Yilmaz,
J. Steven Alexander,
Karen Y. Stokes and
D. Neil Granger
Molecular and Cellular Physiology, Louisiana State University, Shreveport, LA
ABSTRACT
The therapeutic potential of bone marrow stromal cells (BMSC) has been demonstrated in stroke. However there is limited information about the potential neuroprotective factors that BMSC secrete in the infarcted brain. The objective of this study was to isolate BMSC from infarcted regions of the postischemic brain and to compare the expression of genes for extracellular factors produced by transplanted BMSC that have infiltrated brain tissue to 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). BMSC were administered i.v. at 24 h of reperfusion. Mice were sacrificed 1 week after administration of BMSC. Infarcted hemispheres were removed and cultured at 33°C for BMSC isolation. Affymetrix microarray analysis was performed to compare the gene expression patterns between the BMSC populations in 6 mice. Pair-wise analysis detected 93 extracellular factor genes that were upregulated (
2 fold) between naïve and infiltrated BMSC. Fibroblast growth factors, bone morphogenetic proteins, neurotrophic factors, and catalase were among the most highly expressed genes detected. Extracellular factors secreted by protective BMSC following infiltration into postischemic brain may represent novel therapeutic approach for treatment of ischemic stroke.
