Researchers who tried to use mouse, cow and rabbit eggs to make human clones said on Monday the effort failed to produce workable embryos but added that they showed human cloning should work in principle.
Mixing human and animal cells does not appear to program the egg properly, said Dr. Robert Lanza of Massachusetts-based Advanced Cell Technology.
But using human cells did reprogram the egg cell or oocyte and activate the genes needed to make a viable embryo, Lanza and colleagues reported in the journal Cloning and Stem Cells.
Several teams have tried to make animal-human hybrids as a source of embryonic stem cells, the master cells of the body. Because human eggs are scarce — it requires a surgical procedure to get them from a woman — some scientists came up with the idea of using animal egg cells.
The cloning technique is called somatic cell nuclear transfer. The nucleus is removed from an egg cell and replaced with the nucleus from another type of cell from the donor animal or person who is to be cloned.
Done right, the process starts the egg growing and dividing as if it had been fertilized by a sperm, but the resulting embryo carries mostly the DNA of the donor.
“The idea was to simply to plunk a patient’s DNA into an empty cow or rabbit egg — and presto — you reprogram the DNA back into a stem cell,” Lanza said in a telephone interview.
But teams that have tried to do this have always ended up with what looks like a cell dividing over and over to become an embryo, but which eventually fizzles out.
“For the last decade, we’ve carried out literally hundreds of experiments trying to create patient-specific stem cells using animal eggs,” Lanza said.
“We got beautiful little hybrid embryos, but it didn’t work no matter how hard we tried.”
A mouse-human hybrid petered out after just one division. The cow and rabbit human hybrids went further, but stopped at the point when maternal DNA is supposed to kick in and turn the ball of cells into a proper embryo, Lanza said.
Lanza’s team used a new method called global gene expression analysis to see which genes were turned on and off as the eggs grew.
“We never had the tools before to actually look inside the cell and see what’s going on,” Lanza said. It appears that using the egg of another species turns off the genes needed to make an embryo instead of turning them on, he said.
But the human-human clone did turn on the right genes, although it, too stopped dividing before it could produce stem cells, Lanza said.
“We see exactly the same genes turned on in a normal embryo are actually turned on in a human clone,” he said.
Ian Wilmut of the University of Edinburgh, one of the scientists who cloned the first mammal, Dolly the sheep, and editor of the journal, called the results disappointing.
“This very important paper suggests that livestock oocytes are extremely unlikely to be suitable as recipients for use in human nuclear transfer,” Wilmut said in a statement.
But Lanza said it might be possible to use other methods to create “banks” of stem cells that match the several hundred tissue types found among humans.
This could include cloning humans, using a single cell from growing embryos used for fertility treatment, or a new method called induced pluripotent stem cells, made by taking a sample of skin and reprogramming the cells to act like embryonic stem cells, Lanza said.