TORONTO, March 7, 2011 ( – A Toronto-based research team has discovered “worrying” genetic flaws in artificially constructed “pluripotent” stem cells. Dr. Andras Nagy of the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, with Dr. Timo Otonkoski from the Biomedicum Stem Cell Center at the University of Helsinki, have identified genetic abnormalities associated with reprogramming adult cells to become induced pluripotent stem (iPS) cells.

In 2007, when Dr. Shinya Yamanaka of Kyoto University announced that he had discovered how to make embryonic-like stem cells from ordinary adult, or “somatic” human skin cells, the media as well as much of the scientific world hailed it as the discovery that would solve the ethical crisis surrounding stem cell research. But since then, first ethicists, and later other stem cell researchers have warned that there are ongoing problems with the new iPS cells that may strictly limit their usefulness.

The authors of the new research, published this week in the journal Nature, found that the DNA of the cells were shown to be rearranged and to have “copy number variations,” which means that the number of chromosomes in a region of the genome is either reduced or increased.

“The mechanisms underlying the low efficiency of reprogramming somatic cells into induced pluripotent stem (iPS) cells are poorly understood,” write the authors.

The study showed that “significantly more [copy number variations] are present in early-passage human iPS cells than intermediate passage human iPS cells, fibroblasts or human ES cells.”

A complete analysis of the genome should be included in quality control of iPS cells to avoid potential problems, the research team said. “There is a clear need to study whether the reprogramming process itself compromises genomic integrity and, through this, the efficiency of iPS cell establishment.”

“Our analysis shows that these genetic changes are a result of the reprogramming process itself, which raises the concern that the resultant cell lines are mutant or defective,” said Dr. Nagy.

In January it was reported that another team of researchers had discovered potentially serious genetic abnormalities in iPS cells.

The team, led by stem cell scientists at the University of California, San Diego School of Medicine and The Scripps Research Institute, found that the same genetic abnormalities that occur in human embryonic stem cell lines are found in induced pluripotent stem cell (IPSC) lines.

“Since genetic aberrations are often associated with cancers, it is vital that cell lines destined for clinical use are free from cancer-associated genomic alterations,” said senior author Jeanne F. Loring, PhD, professor and Director of the Center for Regenerative Medicine at The Scripps Research Institute.

Stem cell researchers continue to work to find a method to create cells that will be either “pluripotent,” able to be changed into many of the body’s tissue types, or “totipotent.” Totipotent cells are those that can either be turned into any cell type in the body, or develop into a separate organism.

While embryonic stem cells, those taken from an early-stage human embryo, can be changed into a variety of different tissue types, they present a number of medical drawbacks – in addition to the major ethical issues – for treatment of patients, including immune system rejection. At the same time, “adult” or somatic stem cells have been highly successful in experimental treatments of a wide variety of illnesses and injuries, including Parkinson’s disease and spinal cord injuries.


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