Yesterday a New York Stem Cell Foundation team reported for the first time that they had created two new embryonic stem cell lines through a technique known as somatic cell nuclear transfer (SCNT), which is sometimes called therapeutic cloning. They reported their findings in the journal Nature.
SCNT is a third avenue for creating cell lines able to form all tissues in the adult body – called being “pluripotent.” Interestingly, SCNT borrows from the two other techniques used to date.
Pluripotent cell lines were first created by extracting them from 5-6 day old human embryos left over after in vitro fertilization – hence their name human embryonic stem cell lines.
Pluripotent cell lines were later created by reverting skin cells to a pluripotent state through a process called “reprogramming” – commonly referred to as induced pluripotent cells.
SCNT is a reprogramming method that involves the creation of an embryo as a first step. In this case, scientists took DNA from a human skin cell and placed it in a human egg, which they then stimulated to form a 5-6 day old embryo. In this environment, the DNA was reprogrammed to an earlier state and the resulting cells were extracted to create human embryonic stem cell lines.
The fact that SCNT-derived stem cell lines have so much in common with other forms of pluripotent stem cells has some opponents of the research asking why bother? Here’s why. CIRM held a conference in June 2010 to discuss the value of pursuing SCNT and posted a report on the findings in November, 2010.
That report suggests three areas where embryonic stem cell lines generated through SCNT would clearly be valuable in three ways:
- Understanding how you reprogram any cell to become pluripotent could help us optimize the creation of iPS cells, which are so far inefficient to create in addition to being incompletely reprogrammed.
- Understanding and treating the rare diseases that are passed on from those few genes that reside outside the nucleus in the cellular organ called the mitochondria.
- Studying the very early stages of human development, which are poorly understood now, and which is when some human diseases are thought to originate.
The fact that the New York team got the technique to work in humans is a significant advance that has value for all three of those potential areas of research. However, the two cell lines reported yesterday aren’t exactly ready for therapies. Rather than having two copies of each gene, as all of us do, these cells have three copies of every gene and are therefore biologically abnormal. The Wall Street Journal described the problem like this:
While such cloning experiments have been successful in various mammals, the "de-nucleated" egg approach hasn't worked so far in humans. Now, Dr. Egli and his colleagues have—partially—achieved it via a simple move: They didn't remove the egg's own nucleus.
Not removing the egg’s nucleus resulted in the triple copy of chromosomes (one from the egg and two from the donor’s nucleus) that left the cells as “research only” cell lines. Many news stories about the work have referred to the new lines as coming from “cloned embryos”. However, because the cell lines contain more chromosomes than the donor cell they are not truly clones.
Understanding what factors in the nucleus aided in getting SCNT to work could provide clues about factors that might aid in making iPS cells more efficiently, and also provide clues as to how to create SCNT-derived lines with normal numbers of chromosomes.
The Wall Street Journal story quotes George Daly, a stem-cell researcher at Children's Hospital Boston , who summarizes the findings as “a landmark even if it isn’t a complete victory.”
In coming months we should watch for advances that turn this landmark into a victory for people hoping to use the SCNT-derived stem cells to study the earliest stages of development, understand and treat mitochondrial diseases, and learn how to create better iPS cells.
DG
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