Generation of functional hemangioblasts from human embryonic stem cells
Lu, S.J., Feng, Q., Caballero, S., et al. Nature Methods, doi:10.1038/nmeth1041
Seven human embryonic stem cell (h-ESC) lines were induced to differentiate into hemangioblasts under well-defined culture conditions. Specifically, the h-ESCs were grown in a serum-free medium containing bone morphogenic protein-4, vascular endothelial growth factor, stem cell factor, thrombopoietin, and fms-related tyrosine kinase 3 ligand. After two days in this medium, embroid bodies that formed gave rise to blast cells, but an even larger number of blast cells were generated from embroid bodies harvested 3.5 days after exposure to the culture medium. If the h-ESCs were grown for six days in this medium, the embroid bodies yielded only hematopoietic progenitors.
An immunocytochemical analysis found that blast cells exhibited molecular profiles consistent with hemangioblasts, including the expression of SCL, LMO2, and FLT1. Embryonic and fetal globin genes were also expressed, but not adult hemoglobin, suggesting that the cells were at an early developmental stage. Further characterization of the blast cells found that they had the potential to give rise to both hematopoietic and endothelial cells.
The ability of the blast cells to participate in vascular repair was examined in four models: ischemia-reperfusion damage to the retinal vasculature, diabetic retinopathy, myocardial infarction, and hind limb ischemia. Three were conducted in mice, while the fourth, diabetic retinopathy, involved rats. In all cases, blast cells derived from h-ESCs were found associated with areas of vascular repair/growth in the experimental, but not control tissue. Moreover, treatment with the blast cells resulted in the restoration of normal blood flow in the hind-limb ischemic model.
The results of this study suggest that it may be possible one day to prepare blast cells for a variety of therapeutic applications. Indeed, the research was conducted under a collaboration that included Advanced Cell Technology, a development-stage corporation that may seek permission to conduct clinical trials based on these findings in 2008.
Message posted by: Keith Markey
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