One of the great benefits of cell reprogramming–converting adult cells into stem cells–is the ability to capture an individual’s genetic diversity. Scientists are now using this technology, known as induced pluripotent stem (iPS) cell reprogramming, to create banks of stem cells from different people. The banks will be used to test the toxicity of different drugs using cells from people of different ethnicities, and could potentially supply cells for tissue replacement therapies. Researchers presented details of their efforts at the International Society for Stem Cell Research conference in San Francisco this week.
Shinya Yamanaka, a stem cell scientist at the Gladstone Institute, in San Francisco, and Kyoto University, in Japan, first created iPS cells in 2007 by adding just four genes to adult cells that are normally active only in embryos. (James Thomson and Junying Yu at the University of Wisconsin, in Madison, simultaneously published a similar approach.) The cells can reproduce themselves many times over, and they can develop into any cell type in the human body, the two defining characteristics of embryonic stem cells. Furthermore, because they are not made from human embryos, iPS cells bypass the ethical and technical challenges associated with embryonic stem cells.
Scientists have since created iPS cells from patients with different diseases, including amyotrophic lateral sclerosis (ALS) and Parkinson’s disease, and these cells are being used to study these diseases. A number of startups are developing ways to use the cells to screen drugs, both for toxicity in human cells and for their effectiveness in alleviating molecular signs of disease. Jeanne Loring, founding director of the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla, CA, is developing a stem cell bank that will be used for toxicity testing, focusing initially on Africans and African Americans, groups known to have a high level of genetic diversity. Loring and collaborators are analyzing a number of genetic variants in the cells they collect, paying particular attention to variations in drug-metabolizing enzymes that can affect how patients respond to specific drugs, including antidepressants, pain medicines, and drugs for heart disease.
The longer-term goal for iPS cells is to use them to repair or replace damaged or diseased tissue. Just like organ transplants, stem cell transplants must be matched to the recipient. However, Yamanaka points out that creating personalized cells for everyone who needs them is likely to be too time-consuming and expensive to be practical. It can take two to six months to create a line of stem cells from an individual, and someone suffering from spinal cord damage, for example, would likely need a cell transplant within days of injury. (Stem cell treatments for spinal cord injury have not yet been approved by the U.S. Food and Drug Administration, though one company hopes to test embryonic stem cells for this purpose soon.)
Yamanaka’s team is instead working to create a bank of stem cell lines that would be appropriate for a large percentage of the Japanese population. Although the concept of such a stem cell bank was first proposed several years ago for embryonic stem cells, iPS cell technology has made it much easier to create.