Scientists Replicate Diseases In The Lab With New Stem Cell Lines

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Scientists Replicate Diseases In The Lab With New Stem Cell Lines

08 Aug 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 Medical Institute investigator

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.

Medical Institute

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