Induced Pluripotent Stem Cells Retain Cancer Potential

The development of methods to transform normal somatic cells into pluripotent stem cells may help to avoid the controversy surrounding the use of embryonic stem cells in regenerative medicine, but the genetic stability of such transformed cells is a major concern.

The techniques for transforming somatic cells into induced pluripotent stem (iPS) cells have been available for less than 10 years. While it was assumed that the tendency for such cells to become cancerous was less than for human embryonic stem cells (HESC), this point had not been carefully examined.

In the current work, investigators at the Hebrew University of Jerusalem (Israel) focused on this issue by analyzing the chromosomal integrity of 66 HiPSC and 38 human embryonic stem cell (HESC) samples from 18 different studies by global gene expression meta-analysis.

They reported in the October 8, 2010, online issue of the journal Cell Stem Cell that a substantial number of cell lines carried full and partial chromosomal aberrations, half of which were validated at the DNA level. Several aberrations resulted from culture adaptation, and others were suspected to have originated from the parent somatic cell. The analysis indicated high incidence of chromosome 12 duplications, resulting in significant enrichment for cell cycle-related genes.

"The method we have developed for identifying chromosomal changes through gene expression is likely to serve also in other work involving analysis of different kinds of cells, including cancer cells. It is relatively simple to use and enables one to observe the changes without having to directly analyze the DNA of the cells,” said senior author Dr. Nissim Benvenisty, professor of cancer research at the Hebrew University of Jerusalem.

"Our findings show that human iPS cells are not stable in culture, as was previously thought, and require reassessment of the chromosomal structure of these cells,” said Dr. Benvenisty. "Also, our work shows for the first time the gene expression changes that accompany these chromosomal aberrations found in the culture, paving the way for our beginning to understand the mechanism by which these changes occur. The chromosomal changes in these iPS cells require everyone to exercise great care in continuing to work with them, since these changes apparently will influence the differentiation potential and the tumorigenic risk of these cells.”

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Hebrew University of Jerusalem