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Heart muscle cells created directly from adult skin cells  (Source: The Scripps Research Institute)
Improved direct reprogramming strategy skips the iPS stage and converts adult skin cells directly into beating heart cells

Scientists from the Scripps Research Institute have successfully transformed adult skin cells into beating heart cells in mice without having to produce stem cells first. 

Sheng Ding, Ph.D., study leader and a Scripps Research associate professor, along with a team of researchers from both the Scripps Research Institute and the University of California - San Diego, have converted adult skin cells into beating heart cells without having to first create embryonic-like stem cells, which is a difficult and time-consuming process. 

Through a process called differentiation, embryonic-like stem cells multiply and alter themselves into mature cell types as the body develops. This process creates the body's various tissues and cell types, and when the embryonic stage is over, the body has a restricted capacity for new producing new cells when others have been damaged or lost. A team of Japanese researchers accomplished this when they reprogrammed mouse skin cells to be pluripotent through the placement of four genes into the cells. But generating these new cells, which are induced pluripotent stem (iPS) cells, is a whole different story. 

To create iPS cells from skin cells, it takes two to four weeks. Out of the thousands of cells created, only one usually makes it through the transformation. Then the iPS cells have to be induced to differentiate, which takes another two to four weeks. Even when the iPS cells are made and induced, researchers are skeptical about using them because they can harmful. For example, when inducing iPS cells with heart cells, the end result is a combination of the two, which has caused growths that resemble cancerous tumors in mice. 

To remedy all this stress and worry, Ding and his team decided to skip the iPS stage completely and find a way to transform adult skin cells directly into beating heart cells. To do this, they took the four genes that Japanese researchers used to make iPS cells convert into adult skin cells and switched their activity off instead of letting them be continuously active. The genes were turned on for only a few days, and once researchers turned their activity off, the cells were given a signal to make them transform into beating heart cells. 

"It is like launching a rocket," said Ding. "Until now, people thought you needed to first land the rocket on the moon and then from there you could go to other planets. But here we show that just after the launch you can redirect the rocket to another planet without having to first go to the moon. This is a totally new paradigm." 

Ding mentioned that it took only 11 days to turn these skin cells into beating heart cells, and that the signal can be used to turn the cells into brain or pancreatic cells as well. 

"This work represents a new paradigm in stem cell reprogramming," said Ding. "We hope it helps overcome major safety and other technical hurdles currently associated with some types of stem cell therapies."

This study was published in Nature Cell Biology.


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Interesting
By jimhsu on 1/31/2011 7:07:03 PM , Rating: 5
Will read this later, but direct reprogramming has recently (2010) become a hot topic, with the first group (Szabo et al) programming skin cells into blood progenitor cells (Link http://www.nature.com/nature/journal/v468/n7323/fu... ). The primary advantage of this procedure is reduced possibility for hyperproliferation when used in vivo (i.e. cancer), but that also comes at a cost of being more difficult in large quantities efficiently (because of the same proliferation issue).

It'll be interesting to see whether direct reprogramming will win over conventional iPS procedures. Both have been used in only experimental models, so it's too early to tell.




RE: Interesting
By sleepeeg3 on 2/2/2011 10:22:12 PM , Rating: 2
There have been many problems with trying to create iPS cells. Here is a recent article on cells retaining some of their abilities:
http://www.scientificamerican.com/article.cfm?id=f...

Another issue was that some were reverting back to their original progenitor cells several months after being transformed. People need to warm up to the fact embryonic cell research is for everyone's benefit and is far removed from "murder."


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