Scripps research scientists take step in stem cell work

A team led by scientists from The Scripps Research Institute has developed a method that dramatically improves the efficiency of creating stem cells from human adult tissue, without the use of embryonic cells. The research makes great strides in addressing a major practical challenge in the development of stem-cell-based medicine.

The findings were published in an advance, online issue of the journal Nature Methods on Sunday.

The new technique, which uses three small drug-like chemicals, is 200 times more efficient and twice as fast as conventional methods for transforming adult human cells into stem cells (in this case called "induced pluripotent stem cells" or "iPS cells").

"Both in terms of speed and efficiency, we achieved major improvements over conventional conditions," said Scripps Research Associate Professor Sheng Ding, Ph.D., who led the study. "This is the first example in human cells of how reprogramming speed can be accelerated. I believe that the field will quickly adopt this method, accelerating iPS cell research significantly."

In addition to its significant practical advantages, the development of the technique deepens the understanding of the biology behind the transformation of adult human cells into stem cells.

The hope of most researchers in the field is that one day it will be possible to use stem cells - which possess the ability to develop into many other distinct cell types, such as nerve, heart, or lung cells - to repair damaged tissue from any number of diseases, from Type 1 diabetes to Parkinson's disease, as well as from injuries. The creation of iPS cells from adult cells sidesteps ethical concerns associated with the use of embryonic stem cells, and allows the generation of stem cells matched to a patient's own immune system, avoiding the problem of tissue rejection.

The creation of human iPS cells was first announced in December 2007 by two labs, one in Japan and another in Wisconsin. In both cases, the teams used viruses to insert multiple copies of four genes (eg. c-Myc, Oct4, Sox2, Klf4) into the genome of skin cells. These four genes then produced transcription factors turning on and off other genes, and pushing the cell to "dedifferentiate" into stem cells.

While the work was a major breakthrough, it left two major challenges for the field to solve before iPS cell therapy could be considered of any potential practical use. The first involved safety, since the technique relied on potentially harmful genetic manipulation, and worse yet, the insertion of two known cancer-causing genes (c-Myc and Oct4). The second problem was the length and inefficiency of the iPS cell process, which had a success rate of roughly one in 10,000 cells and took about four weeks from start to finish.

Ding and colleagues essentially solved the first problem, the reliance on genetic manipulation, earlier this year in a paper published in Cell Stem Cell (Volume 4, Issue 5, May 8, 2009). In the paper, the researchers demonstrated that they could use purified proteins to transform adult cells all the way back to the most primitive embryonic-like cells, avoiding the problems associated with inserting genes.

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