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A major step in making better stem cells from adult tissue
Date:10/18/2009

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.

In the current paper, the team makes major strides in solving the second problem, efficiency.

A Focus on Natural Processes

In developing the improved method, Ding drew on his knowledge of biology. He decided he would focus his efforts on manipulating a naturally occurring process in cells, in particular in a type of adult cell called fibroblasts, which give rise to connective tissue.

This naturally occurring process called MET (mesenchymal to ephithelial cell transition) pushes fibroblasts closer to a stem-cell-like state. If he could manipulate such a fundamental process to encourage MET and the formation
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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