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Scientists Create New Stem Cell Lines

August 8, 2008

By ELIE DOLGIN and MARK JOHNSON

Harvard scientists have reprogrammed the cells of patients with various genetic illnesses back to an embryonic state, creating a bank of cells that researchers can use to study and fight disease.

The 20 new cell lines span 10 different diseases and conditions, including Parkinson’s and Down syndrome. They will offer scientists the chance to watch diseases progress in a laboratory dish and give researchers new targets for drugs.

These and other cells produced by Harvard scientists will be deposited in the newly founded Harvard Stem Cell Institute “core” facility in Boston, which will serve as a cell bank for reprogrammed embryonic-like stem cells.

“These cell lines will be made available to researchers everywhere,” said institute co-director Doug Melton. “This opens the door to treating degenerative diseases in the years ahead.”

“Part of the goal of creating this repository is to make sure these cells get into the hands of as many researchers as possible,” said George Daley of Children’s Hospital Boston and the Harvard Medical School, who led the study to derive the new cell lines. “It will create a climate of openness.”

The research is published today in the journal Cell.

University of Wisconsin-Madison has been discussing similar plans to create a bank of reprogrammed cells, but “Harvard is definitely ahead of us,” said Clive Svendsen, co-director of UW’s stem cell and regenerative medicine center. He predicted that “there’s going to be enormous demand” for reprogrammed cells.

The creation of the new cell bank brings to fruition an idea scientists were anticipating long before last November’s announcement that skin cells had been reprogrammed back to an embryonic state by separate teams, one led by UW’s James Thomson, the other by Shinya Yamanaka of Kyoto University and the Gladstone Institute of Cardiovascular Disease.

“We’ve been talking about doing this for many years, and here it is,” said Robert Lanza, the chief scientific officer at Advanced Cell Technology in Worcester, Mass.

Daley and his colleagues used a virus to insert three to five genes into either skin cells or bone marrow cells from patients ranging in age from 1 month to 57 years and suffering from different genetic diseases.

The illnesses included heritable single-gene diseases, such as muscular dystrophy; more elaborate genetic conditions, such as Down syndrome; and complex diseases involving both genetic and environmental factors, such as diabetes and Parkinson’s disease.

The researchers ran exhaustive tests to ensure that the reprogrammed cell lines all behaved similarly to embryonic stem cells.

For one cell line — derived from a patient with adenosine deaminase deficiency, or ADA, which causes a severely compromised immune system — Daley’s team also induced the cells to create blood cells. It’s a “proof of principle,” said Daley, showing that tailor- made cells can be matched to each disease type.

“You’re essentially taking a cell that might be difficult to culture,” said Daley, “and you’re taking the patient’s copy, putting it in a petri dish . . . and making a limitless supply of cells.”

Last week, a team led by Harvard’s Kevin Eggan used similar techniques to create reprogrammed stem cells and then motor neurons from patients with Lou Gehrig’s disease. These cells will also be available in Harvard’s new core facility, as well as non-diseased reprogrammed skin cells derived by Daley last December.

By studying the diseases in the lab, and comparing different cell lines from the same disease, scientists hope to gain a better understanding of what goes wrong at the cellular level.

“In these complicated genetic diseases, we’re so ignorant at the moment,” said Melton.

Melton plans to generate 50 diabetes-specific reprogrammed stem cell lines from different patients in the next year.

Harvard’s core facility will have a small staff to help distribute the cells “virtually free,” requiring only a nominal handling fee for all non-commercial, academic researchers. Harvard does not expect anything in return, even if its cells help others make important and lucrative discoveries.

The new cell lines will come with only minimal information about the patient donors, including age, sex and disease diagnosis. But the Harvard scientists plan to obtain more extensive informed- consent medical histories for future cell lines.

The facility itself will also generate 50 to 200 new reprogrammed stem cell lines each year, in addition to hundreds expected to be made in other Harvard labs.

“This is just the first wave of diseases,” Daley said. “I think you’re going to see over time that the number of (reprogrammed stem) cells will match and possibly exceed the number of diseases. And that will be in the many, many thousands.”

“These (cells) are the starting material for research programs,” said Melton. But he said that human embryonic stem cell research is still needed because the cell reprogramming involves viruses and genetic manipulation, which makes the cells potentially cancerous.

Daley added: “At least for the foreseeable future, and I would argue forever, (human embryonic stem cells) will remain to be very useful tools. Whether we’re going to figure out how to do this without viruses so they can be used therapeutically remains an open question.”

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