Stories about: stem cell biology

Improved cell cloning technique makes the jump from mice to humans

cells somatic cell nuclear transfer cloning
(Lonely/Shutterstock)

Roughly a year ago we told you about Yi Zhang, PhD — a stem cell biologist in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine — and his efforts to make a cloning technique called somatic cell nuclear transfer (SCNT) more efficient.

With SCNT, researchers take an egg cell and replace its nucleus with that of an adult cell (such as a skin cell) from another individual. The donated nucleus basically reboots an embryonic state, creating a clone of the original cell.

It’s a hot topic in both agriculture and regenerative medicine. SCNT-generated cells can be used to clone an animal (remember Dolly the sheep?) or produce embryonic stem (ES) cell lines for research. But it’s an inefficient process, producing very few animal clones or ES lines for the effort and material it takes.

Zhang’s team reported last year that they could boost SCNT’s efficiency significantly by removing an epigenetic roadblock that kept embryonic genes in the donated nucleus from activating in cloned cells. Now, in a new paper in Cell Stem Cell, Zhang and his collaborators report that they’ve extended their work to improve the efficiency of SCNT in human cells.

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Removing roadblocks to therapeutic cloning to produce stem cells

Dolly sheep cloning somatic cell nuclear transfer epigenetics
Dolly the sheep, the first mammalian example of successful somatic cell nuclear transfer. (Toni Barros/Wikimedia Commons)

We all remember Dolly the sheep, the first mammal to be born through a cloning technique called somatic cell nuclear transfer (SCNT). As with the thousands of other SCNT-cloned animals ranging from mice to mules, researchers created Dolly by using the nucleus from a grown animal’s cell to replace the nucleus of an egg cell from the same species.

The idea behind SCNT is that the egg’s cellular environment kicks the transferred nucleus’s genome into an embryonic state, giving rise to an animal genetically identical to the nucleus donor. SCNT is also a technique for generating embryonic stem cells for research purposes.

While researchers have accomplished SCNT in many animal species, it could work better than it does now. It took the scientists who cloned Dolly 277 tries before they got it right. To this day, SCNT efficiency—that is, the percent of nuclear transfers it takes generate a living animal—still hovers around 1 to 2 percent for mice, 5 to 20 percent in cows and 1 to 5 percent in other species. By comparison, the success rate in mice of in vitro fertilization (IVF) is around 50 percent.

“The efficiency is very low,” says Yi Zhang, PhD, a stem cell biologist in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine. “This indicates that there are some barriers preventing successful cloning. Thus our first goal was to identify such barriers.”

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