Researchers from the Université libre de Bruxelles(ULB) led by Dr. Cédric Blanpain have isolated the earliest cardiovascular progenitors that arise during the differentiation of pluripotent stem cells.
The heart is composed of different cell types including the contractile muscle cells and the vascular cells. During embryonic development all cardiac cells and certain blood vessels derive from primitive cells known as cardiovascular progenitors.
Pluripotent stem cells and induced pluripotent stem cells (iPS) have the capacity to differentiate into any cell type in the body, including cardiac and vascular cells, which give hope that one day, we can use these cells to replace the death or damaged cells in various diseases. The discovery of novel methods allowing the purification of cardiovascular progenitors during embryonic stem cell differentiation is thus essential before these cells could be used in large scale to treat patients suffering from cardiovascular diseases or for drug discovery.
Researchers led by Dr Cédric Blanpain, FNRS researcher at IRIBHM, Université libre de Bruxelles (ULB), Belgium, studied the mechanisms that govern the specification of cardiovascular progenitors during pluripotent stem cell differentiation. In a new study published in the Journal of Cell Biology, the ULB researchers used genetically engineered embryonic stem cells that become fluorescent when the stem cells become cardiovascular progenitors. By isolating these fluorescent cells, they purified the cardiovascular progenitors and differentiated these cells into beating cardiac cells in vitro and in vivo.
"It was really amazing," commented Dr Antoine Bondue, postdoctoral fellow of the FNRS and first author of this study, "We can now purify the early cardiovascular progenitors and predict in advance which cells will give rise to cardiac cells. It was like dozens of little hearts were beating in the petri dish containing the fluorescent progenitors while no cell was contracting in the dish containing the non fluorescent cells."
Using whole genome analysis of these isolated fluorescent cardiovascular progenitors, the researchers identified novel markers expressed by these cells that allow for their isolation without the need of any other genetic manipulations. This important finding will provide, to the scientific community as well as the pharmaceutical industry, a simple and robust method to isolate cardiovascular progenitors arising from the differentiation of pluripotent stem cells. "This finding will be of great help to upscale the production of cardiovascular cells obtained during pluripotent stem cells differentiation, to better understand what are the conditions needed to amplify cardiovascular progenitors further and how can we push the differentiation of these cells into very specific cardiac or vascular cell types, and hopefully this will accelerate the basic research necessary before the physician will be able to use safely cardiovascular cells to treat patients suffering from cardiovascular diseases, and more importantly to be able to provide to these patients a clear clinical benefit," commented Dr Blanpain.
This work was supported by the Belgian FNRS, a career development award of the Human Frontier Science Program Organization (HFSPO), la Fondation ULB, a starting grant of the European Research Council (ERC) and the EMBO Young Investigator Program.
- A. Bondue, S. Tannler, G. Chiapparo, S. Chabab, M. Ramialison, C. Paulissen, B. Beck, R. Harvey, C. Blanpain. Defining the earliest step of cardiovascular progenitor specification during embryonic stem cell differentiation. The Journal of Cell Biology, 2011; 192 (5): 751 DOI: 10.1083/jcb.201007063
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