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What are induced pluripotent stem cells?
Induced pluripotent stem cells, or iPS cells, are a type of cell that has been reprogrammed from an adult cell, such as a skin or blood cell. iPS cells are pluripotent cells because, like embryonic stem cells, they can develop into virtually any type of cell. iPS cells are distinct from embryonic stem cells, however, because they are derived from adult tissue, rather than from embryos. iPS cells are also distinct from adult stem cells, which naturally occur—in small numbers—in the human body.

In 2006, Dr. Shinya Yamanaka developed the method for inducing skin cells from mice into becoming like pluripotent stem cells and called them iPS cells. In 2007, Dr. Yamanaka did the same with adult human skin cells.

Dr. Yamanaka's experiments revealed that adult skin cells, when treated with four pieces of DNA (now called the Yamanaka factors), can induce skin cells to revert back to their pluripotent state. His discovery has since led to a variety of methods for reprogramming adult cells into stem cells that can become virtually any cell type—such as a beating heart cell or a neuron that can transmit chemical signals. This allows researchers to create patient-specific cell lines that can be studied and used for drug discovery and possibly someday for regenerative medicine.

How are iPS cells different from embryonic stem cells?
iPS cells are a promising addition to embryonic stem cells for tackling human disease in the future. Embryonic stem cells hold tremendous potential for regenerative medicine, in which damaged organs and tissues could be replaced or repaired. But the use of embryonic stem cells has long been controversial. iPS cells hold the same sort of promise and can be made in a patient-specific manner. iPS cells are similar to embryonic stem cells, but some differences remain. Ongoing research, which compares iPS cells to embryonic stem cells, is addressing these differences.

Why is iPS cell technology so important?
iPS cell technology represents an entirely new platform for fundamental studies of human disease. Rather than using models made in yeast, flies or mice for disease research, iPS cell technology allows human stem cells to be created from patients with a specific disease. As a result, the iPS cells contain a complete set of the genes that resulted in that disease—and thus represent the potential of a far—superior model for studying disease and testing new drugs and treatments. In the future, iPS cells could be used in a Petri dish to test both drug safety and efficacy for an individual patient.

Does iPS technology obviate the need for embryonic stem cell research?
Because iPS technology is so new, it is still critical to fund and conduct human embryonic stem cell research. Knowledge gained from research with embryonic stem cells, in part, helped Dr. Yamanaka discover iPS technology. Researchers are still learning many important things about the safest and most efficient ways to create iPS cells for drug discovery, personalized medicine and tissue regeneration. To further refine iPS technology for such promising purposes, scientists still need to measure iPS cells against the "gold standard" of actual human embryonic stem cells.

What has happened since Dr. Shinya Yamanaka developed iPS technology?
There have been several advancements in the field since Dr. Yamanaka first developed iPS cell technology. The most recent advancement is called direct reprogramming, which offers a host of advantages when adult cells are reprogrammed into another type of cell without having to revert back to the pluripotent state. Deepak Srivastava, MD, who directs cardiovascular research at the Gladstone Institutes, earlier this year announced the direct reprogramming of cardiac fibroblasts—the heart's connective tissue—directly into beating cardiac-muscle cells in animal hearts. Also this year, Associate Investigator Yadong Huang, MD, PhD, announced the use of a single genetic factor to reprogram skin cells into cells that develop on their own into an interconnected, functional network of brain cells.

How can iPS cell technology be used in the future?

  1. Regenerative medicine. Gladstone scientists are testing the regenerative effects of iPS cells on animal models. For example, Deepak Srivastava, MD, who directs cardiovascular research at Gladstone, is working on ways to use iPS cell technology to re-grow heart muscles in individuals who have suffered heart attacks. Researchers are also testing whether iPS cell technology can help individuals with spinal cord injuries, as well as neurodegenerative diseases such as Alzheimer's, Huntington's and Parkinson's.
  2. Testing drug safety. Many drugs fail because they cause health problems that are not detected until clinical trials begin. Using iPS cell technology, Gladstone Investigator, Bruce Conklin, MD, is developing heart cells from reengineered adult human cells to test toxicity of drug therapies earlier in the drug-development process—with the goal of reducing the cost and time required for expensive animal and human trials.
  3. Personalized medicine. Drugs interact differently with different patients due to each individual's unique genetic makeup. Using a patient's own cells, researchers could leverage iPS technology to create brain, heart, liver and other cells with that patient's DNA. Those cells could then be used to test potential drug interactions for that specific patient, or someday potentially be used for transplantation or regeneration.
Who is Dr. Shinya Yamanaka?
Dr. Yamanaka is a senior investigator and the L.K. Whittier Foundation Investigator in Stem Cell Biology at the Gladstone Institutes. At Gladstone, he conducts research at the Roddenberry Stem Cell Center. Dr. Yamanaka is also a professor of anatomy at the University of California, San Francisco, as well as the director of the Center for iPS Cell Research and Application (CiRA) and a professor at the Institute for Integrated Cell-Material Sciences (iCeMS), both at Kyoto University, Japan. Before joining Gladstone as a postdoctoral fellow in 1993, Dr. Yamanaka was an orthopedic surgeon practicing in Japan. Leading up to his 2012 Nobel Prize in physiology or medicine, Dr. Yamanaka has received a host of other honors recognizing the importance of his iPS discovery, including the Albert Lasker Basic Medical Research Award, the Shaw Prize, the Wolf Prize in Medicine, the Millennium Technology Award Grand Prize and the Kyoto Prize for Advanced Technology. In 2011, Dr. Yamanaka was elected to the U.S. National Academy of Sciences, garnering one of the highest honors available for U.S. scientists and engineers.

How did Dr. Shinya Yamanaka develop iPS cell technology?
Dr. Yamanaka came to Gladstone in 1993 as a postdoctoral fellow, where he studied cholesterol and fat metabolism. However, after his experiments yielded unexpected results, his focus soon evolved into the study of how stem cells transform into various cell types.

Armed with the expertise he gained at Gladstone, Dr. Yamanaka returned to Japan in 1997 where he developed the innovative method of inducing skin cells into becoming pluripotent, just like embryonic stem cells. He first announced this breakthrough in mice in 2006 and the following year reported that he had done the same with human cells.

Where does Dr. Shinya Yamanaka work?
Dr. Yamanaka splits his time between San Francisco and Kyoto, where he is the director of the Center for iPS Cell Research and Application (CiRA) and professor at the Institute for Integrated Cell-Material Sciences (iCeMS) at Kyoto University. In San Francisco he is a senior investigator and L.K. Whittier Foundation Investigator in Stem Cell Biology at the Gladstone Institutes, where he conducts his research at the Roddenberry Stem Cell Center. He is also a professor of anatomy at the University of California, San Francisco (UCSF).

What is the Gladstone Institutes doing to build on Dr. Shinya Yamanaka's work?
The Roddenberry Stem Cell Center at Gladstone, houses several Gladstone scientists who are building upon Dr. Yamanaka's development of iPS cell technology:

And in July, Dr. Yamanaka's Gladstone lab reported that environmental factors critically influence the growth of iPS cells, taking an important step towards understanding how these cells develop—and towards the ability to use stem cell-based therapies to combat disease.

What is the Gladstone Institutes?
Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Founded in 1979, Gladstone is affiliated with the University of California, San Francisco.