Not all Pluripotent Stem Cells are Equal

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Traditionally, pluripotent stem cells have been considered the most promising candidates for cell therapy due to their ability to develop into any cell type. Among these, embryonic stem cells have been the poster child for the potential of such cells. Because of ethical concerns surrounding the use of embryonic stem cells, however, scientists have instead turned to using alternative methods of obtaining pluripotent stem cells – two of these, namely somatic cell nuclear transfer (SCNT) and induced pluripotent stem cells (iPSC), have grown to particular prominence.

Last week, The Scientist published an interesting article on pluripotent stem cell banks, which are a relatively recent initiative that has appeared in response to the increasing interest in the commercial application and scientific exchange of induced pluripotent stem cells. Started less than five years ago by The National Institutes of Health’s Center for Regenerative Medicine and the New York Stem Cell Foundation, iPSC stem cell banks are rapidly increasing in numbers. Last October, an opinion piece in Nature, titled “What is the point of large-scale collections of human induced pluripotent stem cells?” listed 8 large-scale iPSC banks under development, 4 of which are located in the USA, 3 in Europe and 1 in Japan. The article in the Scientist states there are over 250 cell lines currently deposited in the various banks, but the number is set to exponentially increase over the next few years alone. According to the article:

In most cases, the banks aren’t looking to iPSC lines as profit-generators, but as resources that will hopefully sustain themselves through user fees. […] For now, banks are primarily focused on iPSCs to be used in basic research, disease modeling, and drug screening, rather than for drug development. But therapeutic-grade banks are likely to come next.

Last week, an interesting development in the field of pluripotent stem cells appeared after an article in Nature was published that compared the “pluripotency” of stem cells obtained by somatic cell nuclear transfer and iPSC methods. In somatic cell transfer, the nucleus of an egg cell is replaced with the nucleus of a somatic (adult) cell. Induced pluripotent stem cells are typically obtained by genetic reprogramming of adult cells.

The Nature paper, by a group of researchers from University of California San Diego School of Medicine, Oregon Health & Science Univeristy and the Salk Institute for Biological Studies, reported that pluripotent stem cells obtained by different mechanisms are indeed different. Specifically, the authors generated nuclear transfer ES cell lines and iPS cell lines from the same donor skin cells and compared them to embryonic stem (ES) cells. All cells showed signs of pluripotency, but there were differences in their genetic profiles.

The authors found that DNA methylation profiles of somatic nuclear transfer cells were closer to those of ES cells, while iPS cells displayed DNA methylation patterns typical of adult somatic cells. This prompted them to postulate that pluripotent stem cells obtained by nuclear somatic cell transfer may be more optimal for cell therapy applications.

What implications these finding will have remains to be seen. There are numerous questions regarding the use of somatic transfer nuclear cells in patient therapy that remain unanswered, which is as fundamental as the methods of obtaining them in sufficient numbers, even before questions about their use in transplant medicine can be tackled.

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