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In the essay “Getting Clear on the Ethics of iPS Cells,” Cynthia Cohen and Bruce Brandhorst assert that ES cells (and by inference, iPS cells) are not totipotent because they cannot produce “the extraembryonic tissues required for the development of the fetus.” This oft-repeated claim – which is accepted as conventional wisdom by most bioethicists – is based on the belief that ES cells are incapable of differentiating into trophoblast cells, which are precursors to the placenta. While this may be true for mouse ES cells, it has been falsified in the case of human ES cells. Indeed, in the very first publication from the laboratory of James Thomson that describes human ES cells is the following statement, “After H9 cells were allowed to differentiate for 2 weeks, both alpha-fetoprotein and human chorionic gonadotropin were detected in conditioned culture medium, indicating endoderm and trophoblast differentiation” (Science 282 [1998]: 1145-47). A subsequent paper from the Thomson lab, titled “BMP4 initiates embryonic stem cell differentiation to trophoblast,” provides further details on the ability of ES-derived cells to produce placental-specific proteins (Nature Biotechnology [2002]: 1261-64). The available data do not rule out the possibility that ES cells (and iPS cells) are totipotent.

– Lee Silver
Princeton University

Readers respond

Silver is correct that Thomson’s group reported that human ES cells can be induced to express trophoblast marker genes in culture, though gene expression patterns may not be indicative of full functional differentiation. Rigorous tests in culture and chimeras of the potency of murine embryonic stems cells since then have provided no evidence for their totipotency (reviewed by Rossant in Cell 132 [2008]: 527-31), but there is less information about the properties of human ES cells. Clearly, human and murine embryos, and the ES cell lines derived from inner cell masses of blastocysts, have some distinctive properties, including possibly their potency. However, no one has shown that human ES cells can produce trophoblast and inner cell mass cells in a dish that will then organize themselves into a blastocyst that could implant and develop. The same is true of human iPs cells.

– Bruce P. Brandhorst
Simon Fraser University

– Cynthia B. Cohen, Ph.D., J.D.
Georgetown University

Published on: February 29, 2008
Published in: Emerging Biotechnology

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