Scientists have created viable human embryonic stem cells (ESCs) by transferring the nucleus of a skin fibroblast cell into a donor egg cell. It’s the first successful use of so-called somatic cell nuclear transfer (SCNT) to make human ESCs, although the method has already been optimized in animal models.
Previous attempts to transfer a nucleus into a human donor egg have resulted in embryos that failed to divide into more than eight cells or to become stable stem cells. Because of these challenges, many labs have turned away from SCNT, instead opting to rely on induced pluripotent stem cells (iPSCs). Lacking the built-in pluripotent properties of developing egg cells, iPSCs are created from somatic cells by forcing changes in the expression of key developmental genes.
In studies using macaque cells, Mitalipov’s team discovered that the key to producing viable ESCs was to keep the donor egg stalled in meiosis while the new nucleus was being inserted and other factors were being added. When they applied this knowledge to human cells, they finally began to have success in deriving human ESCs. Their results appear in a paper published today in the journal Cell (1).
“Once we established the whole protocol, we’ve been able to show that in the best case, when we have the best quality oocytes, we could produce ESC lines just using two oocytes,” said Mitalipov.
The researchers went on to show that they could develop ESCs from multiple egg and skin cell donors and that the ESCs had no chromosomal abnormalities or alterations in gene expression. They also confirmed that the mitochondrial DNA was a match to the egg donor, not the new nucleus.
“There is some concern that there is a cross talk between the nuclear genome and mitochondrial genome and this mismatch may create some abnormalities,” said Mitalipov. “But it remains to be seen in the future.” Studies in his own lab of macaques with mitochondrial and nuclear DNA from different sources have shown no problems, he added.
Because ESCs can be coaxed to become any cell type, researchers have long hailed the cells as a way to create personalized disease treatments—new neurons for someone with a neurological condition, for example. And while this new approach to creating human ESCs is years away from having a clinical impact, it is more readily adaptable to basic research than previously developed methods.
Mitalipov’s group is now studying the impact of fibroblast age on the outcome of the process, and he expects other labs develop human ESCs using the new method. “I’m hoping now that we’ve opened up the technology, the technique can be perfected,” said Mitalipov.
- Tachibana, M., Amato, P., Sparman, M., et. al. 2013. Human Embryonic stem cells derived by somatic cell nuclear transfer. Cell 153 (June 6).