EU funded study sheds light on stem cells

A study, set to be presented at an International Symposium coordinated by the University of Sheffield, has shed new light on the properties of induced pluripotent stem cells (iPS cells), reporting evidence that they may not always be able to replace embryonic stem cells (ES cells) in some research and medical applications.

The results of the study by the Hebrew University of Jerusalem and the Children's Hospital in Boston, will be presented in Lisbon at the International Symposium "Stem Cells in Biology and Disease" (26-28 May 2010) organized by ESTOOLS, the largest European consortium of researchers studying human embryonic stem cells. ESTOOLS is coordinated by the University of Sheffield and its partners were the first to be awarded EU funding for studying human iPS cells.

Human iPS cells were discovered in 2007. Like embryonic stem cells, iPS cells can self-renew and turn into any cell or tissue type, but are obtained by genetically reprogramming the somatic cells (internal organs, skin, bones, blood, and connective tissue are all made up of somatic cells) of an individual, raising hopes for their use in research and regenerative medicine without the practical and ethical limitations of embryonic stem cells. iPS cells also provide models for diseases that would be difficult or impossible to study in humans.

Human embryonic and induced pluripotent stem cells show remarkable similarities, however, there is controversy about whether iPS cells are able to fully replace embryonic stem cells in basic research and in clinical applications.

In the new study, published in the 7 May issue of Cell Stem Cell, researchers obtained iPS cells from the skin cells of individuals affected by fragile X syndrome, the most common form of inherited mental retardation in boys, and compared their properties with that of embryonic stem cells isolated from embryos with the same genetic defect (embryos resulted from IVF treatment of a mother carrying the mutation causing fragile X).

Researchers reported that the fragile X gene, called FMR1, was active in embryonic stem cells but not in iPS cells.

Three years ago, the Jerusalem researchers showed that FMR1 was active in human stem cells but not in adult tissue: when stem cells differentiate and turn into mature tissues, epigenetic modifications of the DNA lock down the FMR1 gene, silencing its activity.

Researchers expected that reprogramming adult skin cells back into iPS cells would reset their epigenetic blocks, reactivating the FMR1 gene; instead, they found out that the FMR1 gene resisted reprogramming, and remained inactive in iPS cells, which then failed to faithfully model the natural process.

However, the same iPS cells may be a useful model for studying neurons affected by fragile X, which do not express the gene. It is also possible that other genes may likewise escape the reprogramming process leading to iPS cells.

Nissim Benvenisty, director of the Stem Cell Unit at the Hebrew University of Jerusalem and a leading author of the study, said: "Our findings might underline a more general phenomenon of epigenetic differences between human embryonic and induced pluripotent stem cells.

"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."

Professor Peter Andrews, the Co-ordinator of ESTOOLS and Director of the Centre for Stem Cell Biology at the University of Sheffield, said: "These results from Nissim Benvenisty's group show that human ES cells and iPS cells are complementary tools that in some cases may give different insights into fundamental disease processes. They emphasise the importance of continued research with both types of pluripotent human stem cells. The results also confirm the value and importance of European funding of research consortia like ESTOOLS."

Notes for Editors: The study was partially funded by EU Sixth Framework Programme ESTOOLS. For more information, visit the link below.

ESTOOLS International Symposium will take place at the Gulbenkian Foundation in Lisbon (26-28 May 2010) and will bring together world-renowned experts discussing the latest scientific advances and ethical aspects of human stem cell research. The program will host a range of outreach events for the lay public and the schools, including a premiere of theatre play "Staminalia", the photo-exibition "Smile of a Stem Cell"

REFERENCE: "Differential modeling of Fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells", Achia Urbach, Ori Bar-Nur, George Q. Daley and Nissim Benvenisty, Cell Stem Cell 6, May 7, 2010.

For further information please contact: Shemina Davis, Media Relations Officer, on 0114 2225339 or email shemina.davis@sheffield.ac.uk or Sergio Pistoi, ESTOOLS Media Relations, on +39-3478735664 or email press@sergiopistoi.com or Professor Nissim Benvenisty +972-2-6586774; email: nissimb@cc.huji.ac.il