GLOBAL HEALTH | Addressing the world’s health challenges
30 December 2008
Scientists Generate Stem Cells from Adult Tissue
Breakthrough holds promise for study, treatment of many genetic diseases
Washington — In a triumph of molecular magic, scientists took skin cells from adults suffering from a range of genetic diseases and transformed them into stem cells that could be used to test potential treatments or replace damaged cells in patients.
In its December 19 issue, Science magazine, one of the world’s most prominent scientific journals, hailed this and related advances as the breakthrough of the year, first on a list of the top 10 scientific advances of 2008.
“When Science's writers and editors set out to pick this year's biggest advances, we looked for research that answers major questions about how the universe works and that paves the way for future discoveries,” deputy news editor Robert Coontz said in a December 18 statement. “Our top choice, cellular reprogramming, opened a new field of biology almost overnight and holds out hope of life-saving medical advances.”
Before scientists developed methods to reprogram cells, isolating stem cells from people required harvesting them from human embryos, an ethically controversial procedure. Several countries, including the United States, restricted the technique, thereby hampering stem cell research.
Normally, a mature cell maintains its identity for life — skin cells do not transform into brain cells, muscle cells do not become liver cells. In 2006, researchers turned on four genes in cells from a mouse’s tail and found that the cells had been “reprogrammed” into stem cells — immature cells that have the potential to mature into a variety of different cell types.
Cultured in a dish, stem cells can be incubated with chemical cocktails to coax them to mature into different cell types, including those found in the liver, muscle and brain.
This year’s breakthrough in cellular reprogramming allows researchers to generate new stem cell lines from people with genetic diseases.
“The original embryonic stem cell lines are generic and allow you to ask only basic questions,” George Q. Daley, who leads a multinational group of researchers at Children’s Hospital in Boston and authored one of the studies cited in this year’s breakthrough, said in a press conference in August. “But these new lines are valuable tools for attacking the root causes of disease. Our work is just the beginning for studying thousands of diseases in a petri dish.”
INDUCED PLURIPOTENT STEM CELLS
The roots of this year’s breakthrough date to 2006, when Kazutoshi Takahashi and Shinya Yamanaka at Japan’s Kyoto University identified four genes that, when added to and turned on in cells from an adult mouse, could reprogram them into induced pluripotent stem cells — induced because their creation was not spontaneous, pluripotent because they can become virtually any cell type found in an embryo, fetus or mature organism.
In 2007, researchers generated induced pluripotent stem cells from humans after discovering that the same four genes that reprogrammed mouse cells could also reprogram human cells.
Researchers have taken induced pluripotent stem cell technology further by reprogramming adult cells from humans with diseases, generating lines of stem cells from individuals with neurodegenerative disorders such as Parkinson’s and Huntington’s diseases, two types of muscular dystrophies, diabetes and Down syndrome.
Scientists are coaxing these stem cells to develop into the types of cells most affected by a particular disease. Kevin Eggan and colleagues at Harvard University generated induced pluripotent stem cells from an 82-year-old woman with amyotrophic lateral sclerosis (ALS). These patient-specific cells were cultured in a dish and directed to mature into motor neurons, the cell type destroyed in ALS, whereupon they displayed similar deficiencies to those found in human tissue.
Human cell culture is an “essential complement” to animal models of disease, Daley wrote in the September 5 issue of the journal Cell. Mice, a commonly used animal model, do not always fully mimic human diseases. There is no mouse model of Down syndrome that displays all symptoms of the human condition, for example. Human cell lines permit analysis under controlled conditions and could “undoubtedly provide new insights into disease.”
Although there are many “functional similarities” between embryonic stem cells harvested from human embryos and induced pluripotent stem cells generated from adult tissue, Daley said in a press conference in August that scientists do not yet know whether these two types of stem cells are identical. Research on both types must advance to bring cell therapy to the clinic as quickly as possible.
A SECOND TYPE OF REPROGRAMMING
Douglas Melton and colleagues at Harvard uncovered a second type of cellular reprogramming in which one type of adult mouse cell converts into another cell type directly, without reverting to a stem cell. This recent development could overturn the prevailing scientific wisdom that once a cell matures, its fate is sealed.
Melton and colleagues used a virus to turn on three genes in the mouse pancreas and found that some cells that do not normally produce insulin transformed into cells that do produce insulin. If the toxic effects of viral gene therapy can be overcome, Melton’s work may provide a basis for treating certain types of diabetes, in which cells in the pancreas that produce insulin die and are not replaced.
Despite these recent breakthroughs, scientists understand little about how cellular reprogramming works.
“What are the factors that currently limit cell reprogramming, and how can they be overcome so that large numbers of cells can be induced to reprogram, rather than a tiny minority?” Bruce Alberts, editor in chief of Science magazine, wrote in a December 19 editorial.
To share supplies that might help researchers answer some of these questions, the Harvard Stem Cell Institute established a core facility in July to store and distribute patient-specific stem cell lines.
“The core will also function as a technical laboratory to produce these disease-specific lines for use by scientists around the world,” Melton said in a press conference in August. “We have good reason to believe that this will make it possible to find new treatments, and eventually drugs, to slow or even stop the course of a number of diseases.”
More information about Science magazine’s Breakthrough of the Year 2008 is available on the magazine’s Web site.
