Our laboratory has focused on the contribution of endothelial cells toward normal hematopoiesis. We have demonstrated that normal human hematopoietic stem cells (HSCs) can be expanded 1-2 logs via co-culture with primary endothelial cells in the absence of cell to cell contact. These results are of broad potential significance since few, if any, soluble factors or culture methods have been devised that support a similarly robust expansion of adult human HSCs. Secondly, this HSC-supportive activity is distinctly soluble and elaborated by a novel tissue source (human brain endothelial cells), suggesting the possibility for discovery of novel factors and/or mechanisms which affect HSC self-renewal. Since endothelial cells provide critical signals for the maintenance and expansion of HSCs ex vivo and in vivo, we postulated that endothelial cells might also provide reparative signals to accelerate the recovery of the hematopoietic system following oxidative stress or injury. To test this hypothesis, we recently demonstrated that BM HSC harvested from lethally irradiated (1050 cGy) mice could be functionally rescued and expanded via coculture with primary brain ECs. We have subsequently demonstrated that this pro-survival effect is mediated by EC-conditioned medium (EC-CM) alone, indicating that soluble or secreted factors are responsible for these results.