Chinese Research Teams Build Mice from Reprogrammed Cells, Raising New Bioethical Questions
It turns out that induced pluripotent stem cells are more similar to embryonic stem cells than previously thought—at least in mice. Although iPS cells are not completely identical to embryonic stem cells, two teams of Chinese scientists have been able to demonstrate that reprogrammed cells introduced into an early-stage embryo, or blastocyst, can grow into a live mouse. These proof-of-concept studies are a significant advance, but as Rob Stein at The Washington Post explains: “continued research on embryonic stem cells remains crucial to validate iPS cells and because it remains unclear which cells will turn out to be most useful for different purposes.” The cells in both studies were created by taking mouse connective tissues known as fibroblasts and introducing pieces of genetic material known as the “Yamanaka factors”—named after the lead author on one of the first two iPS studies published by University of Kyoto researcher Shinya Yamanaka in 2007.
The introduction of the key reprogramming genes cause the adult cells to revert back to a pluripotent or embryonic-like state. From there, both Chinese teams used the same technique, known as “tetraploid complementation.” In this process, two cells of a blastocyst are fused together and the iPS cells are then inserted. Since the chromosomes from each of the host mouse’s diploid blastocyst cells, which contain two copies of each chromosome, have been combined into a single tetraploid cell with four copies of each or twice the normal number of chrosmosomes, it cannot replicate and combine its genetic material with the iPS cell. This was a problem in early experiments that introduced iPS cells into blastocysts with only diploid cells, which produced new chimeric mice that possessed cells from two other genetically distinct mice—the mouse that provided the adult cells reprogrammed into iPS cells, and the mouse that supplied the blastocyst. In the tetraploid blastocyst, the genetic material from the mouse that supplied the blastocyst simply grows into placental tissues and the new embryo only possesses the genes from the iPS cells.
While both teams behind the studies published last week demonstrated that it is possible to grow live mice from reprogrammed cells, the group from the Institute of Zoology in Beijing and Shanghai Jiao Tong University managed better results, with a total of 27 live births. According to Nature News, “With their best cell line and optimal recipe, they were able to get 22 live births from 624 injected embryos, a success rate of 3.5%.” Their research appeared in Nature. The other team, from the National Institute of Biological Sciences in Beijing, published their study in the journal Cell Stem Cell and was able to get two live births from 187 attempts. However, one died in infancy.
Robert Blelloch of the University of California San Francisco’s Broad Center for Regeneration Medicine and Stem Cell Research told the Los Angeles Times that these studies can be characterized as a “brute force effort” since the basic technique was the same as previous unsuccessful attempts, but the teams just tried it over and over again with incremental changes until it worked.
This new research changes the bioethical landscape by demonstrating that, at least in mice, any somatic cell from an organism can be used to clone that organism. This is significant for ethicists who fall anywhere along the political spectrum—despite the fact that no reputable scientists are interested in cloning people, and given the low success rate and high death rate of the cloned mice using the new technique, this is something that would be grossly unethical to try in humans.
SP Editor-in-Chief Jonathan Moreno discussed the unforeseen ethical implications of advances such as this, which render every adult cell in the body a potential embryo in Science Next—a scientific possibility that conservative bioethics might fear even more than embryo destruction. You can read a long excerpt of his analysis here.
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