Scientists replicate diseases in the lab with new stem cell lines

Aug 07, 2008

A set of new stem cell lines will make it possible for researchers to explore ten different genetic disorders—including muscular dystrophy, juvenile diabetes, and Parkinson's disease—in a variety of cell and tissue types as they develop in laboratory cultures.

Researchers led by Howard Hughes Medical Institute investigator George Q. Daley have converted cells from individuals with the diseases into stem cells with the same genetic errors. These newly-created stem cells will allow researchers to reproduce human tissue formation in a Petri dish as it occurs in individuals with any of the ten diseases, a vast improvement over current technology. Like all stem cells, these disease-specific stem cells grow indefinitely, and scientists can coax them into becoming a variety of cell types.

Daley, who is at Children's Hospital Boston, worked with researchers from Harvard Medical School, Massachusetts General Hospital, and the University of Washington to create the disease-specific stem cell strains. The scientists will make the cell lines available to scientists worldwide through a core facility funded by the Harvard Stem Cell Institute. Daley and his colleagues published the details of the disease-specific stem cell lines in an advanced online publication of the journal Cell on August 7, 2008.

"Researchers have long wanted to find a way to move a patient's disease into the test tube, to develop cells that could be cultured into the many tissues relevant to diseases of the blood, the brain and the heart, for example," he says. "Now, we have a way to do just that—to derive pluripotent cells from patients with disease, which means the cells can make any tissue and can grow forever. This enables us to model thousands of conditions using classical cell culture techniques."

Daley's team has created disease-specific stem cell lines for Duchenne muscular dystrophy; Becker muscular dystrophy; juvenile-onset (type I) diabetes; Parkinson's disease; Huntington's disease; Down's syndrome; ADA severe combined immunodeficiency (a form of the disorder commonly known as "boy-in-the-bubble disease"); Shwachman-Bodian-Diamond syndrome (which causes bone marrow failure and a predisposition to leukemia); Gaucher disease (an inherited metabolic disorder in which a fatty substance accumulates in several of the body's organs); and Lesch-Nyhan syndrome (an enzyme deficiency that causes a build-up of uric acid in body fluids). Many more cell lines are possible.

For years, researchers have grown human cells in the laboratory in an attempt to mimic various genetic diseases, but the available techniques had significant shortcomings. Cells taken directly from affected patients typically have a limited lifespan when grown in laboratory dishes, restricting the types of studies for which they can be used. Researchers often turn to cells that have been modified to make them live in a dish forever, but altering cells to make them immortal changes their physiology and can cast doubt on a study's results.

Recently, Daley's lab and others have demonstrated that adult cells can be converted to stem cells by introducing a set of genetic "reprogramming factors." To produce the disease-specific stem cells, Daley and his colleagues mixed cells from patients with the ten disorders with benign viruses to introduce the reprogramming factors into the cells. The resulting stem cells harbored the genetic diseases of the donors.

Once the researchers isolated the disease-specific stem cells, they analyzed the genes and confirmed that the stem cells had the same disease-causing defects as the original donor cells. The researchers also made sure that the stem cells were pluripotent—able to differentiate into many different tissue types.

Daley says that in many cases these new stem-cell cultures will mimic human disease more reliably than animal models. Despite the vast genetic similarities between humans and mice, physiological differences invariably affect the course of disease in a mouse. In some cases, the genetic defect that produces a disorder in humans—such as Down's syndrome—does not cause the same symptoms in mice. Therefore, human cell cultures are an essential complement to research with animal models, Daley says.

The most immediate application of the disease-specific stem cells will be to reproduce human diseases in culture to explore their development in different tissues, Daley says. The technique will even enable researchers to compare how the same disease varies among people, by generating disease-specific stem cell cultures from many individuals. The cells will also offer a proving ground for screening drugs to treat disease.

Over the longer term, Daley expects the technique will be applied clinically. For example, it may allow scientists to develop therapies using a patient's own cells--reengineering the cells to correct a disease-causing defect then re-introducing them into the body.

The Harvard Stem Cell Institute will make the stem cell lines available to the scientific community as quickly as possible, Daley says. The institute will also continue to work to generate cell lines for other diseases.

Daley and his colleagues' techniques for reprogramming adult cells are readily available so other researchers can generate their own disease-specific stem cell lines. However, "Stem cells are quite finicky," Daley cautions. "They don't grow like weeds; they're more like orchids. You really have to tend to them." Therefore, he plans to collaborate with researchers at other institutions to help produce stem-cell lines for the diseases they want to study.

Source: Howard Hughes Medical Institute

Explore further: Researchers collect soil samples from around the globe in effort to conduct fungi survey

add to favorites email to friend print save as pdf

Related Stories

Genomes of malaria-carrying mosquitoes sequenced

1 hour ago

Nora Besansky, O'Hara Professor of Biological Sciences at the University of Notre Dame and a member of the University's Eck Institute for Global Health, has led an international team of scientists in sequencing ...

Bitter food but good medicine from cucumber genetics

1 hour ago

High-tech genomics and traditional Chinese medicine come together as researchers identify the genes responsible for the intense bitter taste of wild cucumbers. Taming this bitterness made cucumber, pumpkin ...

Education is key to climate adaptation

1 hour ago

Given that some climate change is already unavoidable—as just confirmed by the new IPCC report—investing in empowerment through universal education should be an essential element in climate change adaptation ...

Recommended for you

Parasitic worm genomes: largest-ever dataset released

9 hours ago

The largest collection of helminth genomic data ever assembled has been published in the new, open-access WormBase-ParaSite. Developed jointly by EMBL-EBI and the Wellcome Trust Sanger Institute, this new ...

Male sex organ distinguishes 30 millipede species

9 hours ago

The unique shapes of male sex organs have helped describe thirty new millipede species from the Great Western Woodlands in the Goldfields, the largest area of relatively undisturbed Mediterranean climate ...

How can we avoid kelp beds turning into barren grounds?

13 hours ago

Urchins are marine invertebrates that mould the biological richness of marine grounds. However, an excessive proliferation of urchins may also have severe ecological consequences on marine grounds as they ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.