Scientists have created embryonic stem-cell lines that are a perfect tissue match to their mouse donors, allowing the cells to be transplanted without immune rejection. If similar methods succeed in humans, the technique could provide a way to generate patient-matched cells for transplant that doesn’t require destruction of viable human embryos. “This presents a much more efficient way … of generating tissue-matched embryonic stem cells,” says George Daley, a physician and researcher at Children’s Hospital Boston and lead scientist on the project.
Scientists one day hope to use stem-cell-derived therapies to replace lost or diseased cells, such as in Parkinson’s disease or sickle-cell anemia. But just as with organ transplants, these cells must be closely matched to the recipient’s genetic profile in order to avoid immune rejection. Currently, the best method for generating genetically matched cells is cloning or nuclear transfer, in which an adult cell from the donor is inserted into an egg that has had its DNA removed, generating an embryo genetically identical to the one from the adult donor. In 2002, Daley and collaborators showed that customized stem cells generated via cloning could be implanted in mice to cure genetic deficits.
But cloning, which often requires a large number of eggs, is a technically challenging and inefficient way to make stem cells, and it raises ethical objections because it requires destruction of a human embryo. An alternative is to generate cells using parthenogenesis, a form of asexual reproduction in which an embryo can develop without fertilization. Parthenogenesis occurs naturally in some plants and vertebrates, but not in mammals. However, scientists can trick mammalian eggs into undergoing parthenogenesis by activating the egg as if it had been fertilized. To date, such embryos have been generated in mice, primates, and even humans. Human versions of these embryos are called parthenotes; they survive only a few days and are therefore unable to develop into a human life.
While scientists have previously been able to generate stem cells from mice via parthenogenesis, the new study provides a way to select cells that are a perfect tissue match to the donor. “It’s the first time parthenote-derived cells have been successfully transplanted and tolerated in mice,” says Kent Vrana, a molecular biologist at Penn State University. “This work is important because it shows you can select parthenotes for [tissue] compatibility.”
Daley cautions that many tests still need to be done before such therapies can be developed for patients. For example, since parthenote cells carry two sets of maternal genes, they may have abnormal gene expression. “We will try to determine if cells made from parthenotes will function normally,” says Daley.
Daley’s primary interest is in developing better therapies for blood diseases, such as leukemia. While bone-marrow transplants present an effective treatment for leukemia, many people can’t find donors whose bone marrow is a close enough match to be suitable for transplant. The team is now testing bone-marrow transplants from parthenote-derived stem cells in mice and is trying to create parthenote-derived stem cells from human eggs.
It’s not clear if the results will easily translate to humans, says Robert Lanza, vice president of scientific research at Advanced Cell Technologies, an Alameda, California-based company developing stem-cell therapies. While scientists have previously been able to generate stem cells from a primate parthenote, the process has proved elusive in human cells. For the most part, human parthenotes do not survive long enough for scientists to harvest the cells from which stem cells are derived. In July, a group of Italian scientists announced at a meeting that they had derived a line of stem-cell-like cells from a human parthenote, but the work has not yet been published in a scientific journal.
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