Human embryonic stem cell-derived hematoendothelial progenitors engraft chicken embryos

Objective. To investigate whether human embryonic stem cells (hESC) committed in culture into hematopoietic/endothelial cell progenitors can be further developed into mature blood and vascular cells following transplantation into chicken embryos. Materials and Methods. The yolk sac of 42- to 44-hour chicken embryos received yolk sac injections of unfractionated human embryoid body (hEB) cells, CD34-positive hEB cells, or CD34(+)CD45(+) granulocyte colony-stimulating factor-mobilized human peripheral blood hematopoietic stem-progenitor cells. Human cells in the host were detected by How cytometry and immunohistochemistry. Results. All injected cell populations engrafted chicken hematopoietic organs, its assessed by detection of CD45(+) cells in the spleen, bursa of Fabricius, and thymus. CD34(+) day -10 hEB cells showed the highest efficiency for producing human CD45(+) cells in the hosts and yielded human glycophorin A(+) erythroid, CD13(+) myeloid, and CD19(+) lymphoid cells in the spleen and bursa of Fabricius. Spleen cells from chimeric embryos also contained human colony-forming units-granulocyte macrophage, as assessed in methylcellulose colony-forming assays. Human endothelial cells expressing vascular endothelial-cadherin, von Willebrand factor, CD31, and the receptor for the Ulex europaeus lectin were also observed in the yolk sac vasculature following injection of either unfractionated or CD34(+) day -10 hEB cells. Conclusion. Primitive angiohematopoietic stem cells (total and CD34(+) (lay -10 Wit cells) as well as adult hematopoietic stem cells could home to intraembryonic blood-forming organs following injection into the yolk sac. These observations demonstrate the utility of the avian embryo as a convenient and reliable host to model the angiohematopoietic development of human embryonic, or other early stem cells. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.