Posted on behalf of Monya Baker
The ability to make custom-order stem cells for drug discovery or regenerative medicine now appears more complex. Adult-derived cells reprogrammed to behave like embryonic stem cells act differently depending on where the cells came from, according to papers published today in Nature and Nature Biotechnology.
The production of induced pluripotent stem (iPS) cells revolutionized the stem cell field by promising a way to produce tissues genetically matched to any patient. Previously, the only way to do so was thought to be creating embryonic stem cells by somatic cell nuclear transfer (SCNT), or moving the nucleus from one cell into an enucleated, unfertilized egg, which then grows into an embryo from which stem cells can be derived.
Working in mice, George Daley and colleagues at Children’s Hospital Boston compared embryonic stem cells from SCNT and iPS cells derived from different tissues (doi: 10.1038/nature09342). SCNT-derived cells behaved more like other embryonic stem (ES) cells, while iPS cells were more able to make cells from their tissue of origin. In separate work looking at iPS cells, Konrad Hochedlinger and colleagues at Harvard University also saw that what tissue the original cells came from determined how the cells behave (doi: 10.1038/nbt1667). The reason seems to be that iPS cells do not entirely erase their epigenetic markings, modifications that specify which genes are used by a particular cell.
In both cases, the researchers showed that the epigenetic modifications could be overcome. But researchers are still improving reprogramming techniques. “Embryonic stem cells remain the gold standard against which iPS cells are measured," says Daley. "Nuclear transfer may yet still teach us lessons that will help us make better iPS cells.”
Nuclear transfer, which has not worked in human cells, is controversial because it requires women to donate unfertilized eggs and creates an early-stage embryo only to destroy it. Interest in SCNT declined precipitously after the advent of iPS cells.
The desire to compare iPS cells and SCNT-derived stem cells could reignite debate about whether such SCNT stem cells should be studied with U.S. federal research dollars. Currently research funding is only allowed on human ES cell lines made from embryos created for reproductive purposes but no longer wanted for reproduction and freely donated for research. Recently, the National Institutes of Health adopted a tough stance against funding lines derived with inadequate informed consent, a move that may give the NIH more leverage and credibility if it reconsiders whether to fund SCNT ES cells in light of the value such studies could provide.
Ultimately, the two papers could help make iPS cells more useful. Most scientists don’t want to study iPS cells as much as cells derived from them. Researchers can rarely obtain neurons directly from patients with degenerative disease, for example, but they can make neurons from iPS cells derived from the patients. This allows studies that were previously impossible. However, researchers can also have trouble making sufficiently pure and high-quality cells from iPS cells. Better ways to do would be valuable indeed.