Scientists at Stanford University School of Medicine say they have taken a major step toward the use of adult cells reprogrammed into an state that allows them to develop into virtually any cell type in the body through the development of a technique they say is easy and safe and could ease the way for the therapeutic use of these cells by the U.S. Food and Drug Administration.

 

The researchers used tiny circles of DNA to transform stem cells from human fat into induced pluripotent stem cells for use in regenerative medicine. Unlike other commonly used techniques, the method, which is based on standard molecular biology practices, does not use viruses to introduce genes into the cells or permanently alter a cell's genome. It is the first example of reprogramming adult cells induced to pluripotency in this manner.

 

“This technique is not only safer, it’s relatively simple,” says Stanford surgery professor Michael Longaker, co-author of the paper published online in Nature Methods. “It will be a relatively straightforward process for labs around the world to begin using this technique. We are moving toward clinically applicable regenerative medicine.”

 

The Stanford researchers used the so-called minicircles – rings of DNA about one-half the size of those usually used to reprogram a cell – to induce pluripotency in stem cells from human fat. Pluripotent cells can then be induced to become many different specialized cell types. Although the researchers plan to first use these cells to better understand, and perhaps one day treat, human heart disease, the so-called induced pluripotent stem cells, or iPS cells, are a starting point for research on many human diseases.

 

“Imagine doing a fat or skin biopsy from a member of a family with heart problems, reprogramming the cells to pluripotency and then making cardiac cells to study in a laboratory dish,” says Joseph Wu, a cardiologist and senior author of the study. “This would be much easier and less invasive than taking cell samples from a patient's heart.”

 

The minicircles were developed at Stanford several years ago in an effort to develop suitable gene therapy techniques. The researchers say the minicircle reprogramming vector works so well because it is made of only the four genes needed to reprogram the cells (plus a gene for a green fluorescent protein to track minicircle-containing cells).

 

Unlike the larger, more commonly used DNA circles called plasmids, the minicircles contain no bacterial DNA, meaning that the cells containing the minicircles are less likely than plasmids to be perceived as foreign by the body. The expression of minicircle genes is also more robust, and the smaller size of the minicircles allows them to enter the cells more easily than the larger plasmids. Finally, because they don't replicate they are naturally lost as the cells divide, rather than hanging around to potentially muck up any subsequent therapeutic applications.