Somatic cell nuclear transfer (SCNT) is a technique in which the nucleus of a donor cell is transferred to an egg cell whose nucleus has been removed, generating embryos that are almost an identical genetic match to the donor individual. For the first time, a team of scientists has used SCNT to produce human embryonic stem cells (hESCs). This milestone, published by Cell Press May 15th in the journal Cell, opens up new avenues for using stem cells to understand patient-specific causes of disease and for developing personalized therapies.
"Our finding offers new ways of generating stem cells for patients with dysfunctional or damaged tissues and organs," says senior study author Shoukhrat Mitalipov of Oregon Health & Science University. "Such stem cells can regenerate and replace those damaged cells and tissues and alleviate diseases that affect millions of people."
Another technique that has been used to generate patient-specific stem cells to model diseases is called induced pluripotent stem cells (iPS) cells, which are generated directly from the patient's somatic cells by adding a cocktail of cellular factors to stimulate regression to a stem cell state. However, concerns that this technique may generate unexpected mutations in the stem cells means that researchers are still keen to find ways to generate hESCs by other means.
In the past, researchers have used SCNT to generate only mouse and monkey embryonic stem cells—immature cells that can develop into different types of specialized cells, from neurons to heart muscle cells. Most previous attempts failed to produce human SCNT embryos that could progress beyond the 8-cell stage, falling far short of the 150-cell blastocyst stage that could provide hESCs for clinical purposes. Until now, it was not clear which factors and protocols are important for promoting SCNT embryonic development.
To overcome these hurdles, Mitalipov and his team started in familiar territory, refining methods for producing monkey SCNT embryos. Using these optimized protocols, they transferred nuclei from human skin cells into the cytoplasm of human egg cells, generating blastocysts that gave rise to hESC colonies. The resulting hESCs resembled those derived from fertilized embryos, had no chromosomal abnormalities, showed normal gene activity, and were capable of turning into more specialized cell types that could be used for replacing damaged tissues.
Surprisingly, the best outcomes came from donors who produced a low number of high-quality egg cells. "It was thought that, to make human SCNT work, many thousands of human eggs would be needed," Mitalipov says. "We were able to produce one ESC line using just two human eggs, which would make this approach practical for widespread therapeutic use."
Cell, Tachibana et al.: "Human embryonic stem cells derived by somatic cell nuclear transfer."