Thriving stem cells created by cloning technique

By Dr. Ananya Mandal, MDOct 6 2011

In a breakthrough that has been debated and awaited for long, scientists have finally derived colonies of embryonic stem cells from human embryos created using cloning technology.

The experiments appeared in the journal Nature, where the team of scientists from the New York Stem Cell Foundation Laboratory claim they created two lines of the cells through the use of somatic cell nuclear transfer (SCNT), the other term for cloning.

SCNT is a technique in which an adult cell is fused with an egg and activated to make an embryo — to create stem cells that match patients. Scientists hope the cells could one day be used to treat or even cure diseases like diabetes, and usher in an era of so-called “regenerative medicine.”

However unlike normal stem cells, the cells obtained by the team also included DNA from the human eggs used in the process, resulting in a highly abnormal 69 chromosomes rather than the usual 46. That makes the cells useless for therapy, but, argued lead scientist Dieter Egli in a press conference with reporters, the cells can be used “to address important questions, like asking how these cells compare to [other stem-like cells]…We now have a reliable assay to build on to conduct future research.”

Larry Goldstein, director of the University of California San Diego Stem Cell Program, agreed that the experiment represents a significant accomplishment. “It’s not going to lead to a therapy,” he said. “But from a longer term perspective, it is very important.” It will help bring out the reasons why human SCNT has been so difficult.

Unlike SCNT in other animals that have been cloned, the New York team demonstrated that certain factors in the human egg’s nuclear DNA are required to make resulting stem cells viable. “When we first removed the [egg] genome and replaced it with the genome of the skin cell, development [of the embryo] arrested after a few divisions,” Egli said. So they left the egg’s DNA in place. That way, whatever gene products that make the difference between survival of embryos and stem cells — what those are haven’t been identified — would still be present he explained.

Gerald Schatten, director of the Division of Developmental and Regenerative Medicine at the University of Pittsburgh School of Medicine spoke of his own past work suggested that it might be necessary to leave an egg DNA structure called the meiotic spindle intact if the embryo was to develop and the resulting stem cells live. In light of this new paper, he wrote in an email, “it is reasonable to conclude that primate eggs (human and non-human alike) differ from mice and other rodents, and also eggs from domestic species” like cows and pigs.

The Egli team used skin cells from an adult diabetic and a healthy control. Researchers started with 270 eggs and eventually created two stem cell lines, according to study co-author Scott Noggle, director of the New York Stem Cell Foundation lab where the work was done. By leaving the egg’s genome intact, the scientists were able to make human cloning about as efficient as animal cloning. They got 13 blastocyst stage embryos from 63 eggs. From those 13, they derived one stem cell line that matched each donor. Analysis proved that the cells were fully reprogrammed by the eggs, giving them a development do-over.

But one of the key accomplishments of the experiment isn’t scientific at all, it’s ethical, according to  Alan Trounson, president of the California Institute for Regenerative Medicine. Human eggs are difficult to come by, a fact that Trounson thinks has stymied some research. But the New York foundation asked female patients of Columbia University’s IVF program who had already agreed to donate excess eggs harvested during procedures if they would like to divert some of those eggs to research.  

Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, said this new work shows how hard it would be to use cloning to create people. That avoids a major ethical concern with embryonic stem cells, he said.