Stem Cell Briefings, International Society for Stem Cell Research
(Originally published at theISSCR website
The groundbreaking discovery of human induced pluripotent stem cells (iPSCs; see Briefing: Breakthroughs in Stem Cell Biology) has revolutionized the field of regenerative medicine, opening new avenues for research and for future clinical applications. These cells share many features with embryonic stem cells (ESCs), including the ability to turn into virtually any cell type, but unlike their ESC counterparts, are obtained by reprogramming adult cells from an individual, avoiding the difficulties and ethical issues of sourcing and using embryos. Unsurprisingly, human iPSCs have become a topic of interest for those interested in modeling diseases, and are also used as an argument by those opposed to using human ESCs for ethical or religious reasons. If the two types of cells were the same, then pursuing research on cell lines that are obtained from human embryos could possibly be avoided. A workshop organized last May during the final meeting of the EU-funded project ESTOOLS in Lisbon, and chaired by University of Lund’s bioethicist Göran Hermerén, specifically addressed the question of whether iPSCs might be able to replace ESCs (1).
While it is true that there are striking similarities between human iPSCs and ESCs, the workshop reviewed a number of scientific studies that unveil subtle but fundamental differences between the two types of cells. The results of these studies have led many in the stem cell research community to conclude that human iPSCs are not ready to fully replace their embryonic counterparts.
Nissim Benvenisty from the Hebrew University of Jerusalem, who reported his results in Lisbon, recently compared iPSCs and ESCs taken respectively from patients and embryos affected by fragile X syndrome, the most common form of inherited mental retardation in boys, and discovered that the gene responsible for the syndrome behaved differently in the IPSCs and ESCs. Benvenisty, who published his results last May in the journal Cell Stem Cell (2) concluded that, at least for fragile X syndrome, iPSCs do not model the disease as faithfully as their embryonic counterparts. “Until we understand better the differences between these two types of cells, the optimal approach might be to model human genetic disorders using both systems, whenever possible”, he said.
Benvenisty is only one of many experts cautioning against the idea of putting iPSCs and ESCs in the same basket. A news story in Science (3) made a stir earlier this year reporting on two studies in which iPSCs and ESCs were compared side-by-side. Both concluded that there were differences in how the iPSCs and ESCs developed into specialized cell types and how the resultant specialized cell types functioned. Robert Lanza, a leading author of one of the studies, was quoted as describing their iPSCs as “pretty screwed up” compared to their embryonic counterparts. The article reported other observations, including those by Prof. Shinya Yamanaka (the first to generate iPSCs), suggesting that iPSCs and ESCs are not always equivalent.
Marc Peschanski from the I-STEM Institute in Paris, whose group was the first to obtain human epidermis from ESCs (4), reported in Lisbon that, when he tried to obtain epidermal cells from iPSCs cells, the efficiency was about half than with ESCs. IPSCs also matured faster and formed a thinner layer of skin compared to ESCs. “It is not clear if such differences are intrinsic to iPSCs or are due to the reprogramming protocols that need to be improved”, said Peschanski.
Debates over the use of human ESCs will not end soon, and human iPSCs will continue to provide huge value to many researchers. However, if we look at the scientific evidence, it remains too early to dismiss hESCs altogether.
Sergio Pistoi, Ph.D.
Freelance science writer and communication consultant.
Note: the Author worked as a consultant for the ESTOOLS project.
ESTOOLS International Symposium “Stem Cells in Biology & Disease” and 3rd ESTOOLS Ethics Workshop, Lisbon, 26-28 May 2010. http://www.estools.eu/Lisbon. Accessed September 15, 2010
Urbach, A., Bar-Nur, O., Daley, G. Q., and Benvenisty, N. (2010). Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell 6, 407-411.
Vogel, G. (2010). Stem cells. Reprogrammed cells come up short, for now. Science 327, 1191.
Guenou H., Nissan X., Larcher F., Feteira J., Lemaitre G., Saidani M., Del Rio M., Barrault C.C., Bernard F.X., Peschanski M., Baldeschi C., Waksman G. (2009). Human embryonic stem-cell derivatives for full reconstruction of the pluristratified epidermis: a preclinical study. Lancet 374, 1745-53.