CAIRNS, AUSTRALIA--In a stunning breakthrough, researchers report deriving embryonic stem (ES) cells from cloned monkey embryos. Because of the similarities between monkeys and humans, the advance--announced here yesterday at the 5th International Society for Stem Cell Research meeting--could pave the way for stem cell therapies that could be tailored to specific people.
Cloning--also known as somatic cell nuclear transfer (SCNT)--involves inserting the DNA-filled nucleus of a body cell into an egg whose nucleus has been removed. The reconstituted egg is then allowed to develop into an embryo. Stem cells from these cloned embryos are a Holy Grail for medical research because they would provide perfectly matched tissue grafts for the body cell donor. Scientists have produced live young--as well as ES cell lines--via cloning in many species. But primates have proven a challenge; disgraced Korean researcher Woo Suk Hwang was unable to generate human ES cell lines with the technique, despite having access to more than 2000 human oocytes (ScienceNOW, 28 November 2006).
Now, embryologist Shoukhrat Mitalipov of the Oregon National Primate Research Center at Oregon Health and Science University claims to have met that challenge using a modified version of the SCNT approach. Instead of staining the oocyte nucleus with a DNA dye and visualizing it with ultraviolet light--a technique Mitalipov believes damages fundamental reprogramming factors--his team used a polar microscope, which illuminates the oocytes with nondestructive, polarized light. The researchers also inserted the donor skin nucleus into the oocyte by direct injection rather than jolting the cells with electricity to fuse the donor cell to the enucleated oocyte. Mitalipov said the latter approach, called electrofusion, may prematurely activate the reconstituted egg, causing it to start dividing before the chromosomes are ready.
Using the modified strategy on skin cells from a 10-year-old male rhesus monkey, Mitalipov says his team has generated 20 cloned blastocysts and ultimately two lines of cloned rhesus ES cells. These lines pass a number of the standard tests for ES cell lines, Mitalipov reported. For example, they show the characteristic surface proteins that indicate the cells' ability to replicate indefinitely. Mitalipov also presented evidence that the cells can differentiate into a variety of cell types, such as heart and nerve cells. The cells also formed tumors composed of several types of tissues when injected into mouse testes--another standard test of pluripotency.
"This is a beautiful work, really well done," says embryologist Megan Munsie of the Australian Stem Cell Centre in Melbourne. If it is repeated by other groups, it brings the possibility of doing SCNT with humans much closer, she says. But some researchers remain skeptical. Hematologist Irving Weissman of Stanford University in Palo Alto, California, points out that Mitalipov did not test the cells for their ability to become incorporated into tissue when mixed with a normal embryo, a key feature of ES cells. "A lot of us are puzzled," adds cloning expert Robert Lanza of Advanced Cell Technology in Worcester, Massachusetts. "There has to be more to this [approach] than using the polar scope."