Harvard Researchers Create Disease-Specific Cell Lines

It won't be long before scientists can order shipments of disease-specific cell lines from the Harvard Stem Cell Institute (HSCI) so that they can study diseases in Petri dishes, according to a new study released by scientists at HSCI.

Harvard researchers have already created stem cells for ten genetic disorders using a new technique that isolates human induced pluripotent stem (iPS) cells. The technique allows scientists to genetically manipulate a patient's cells—typically skin cells or blood cells—and reprogram them into a pluripotent state; like embryonic stem cells, these iPS cells are then capable of morphing into any type of body tissue.

"This has really been one of the goals of stem cell biology for many years—to be able to produce customized disease-specific lines for different patients," said George Q. Daley, a member of the executive committee of HSCI and the senior author of the paper, which was published on the Web site of the journal Cell earlier this month.

Daley, who is also a professor at Harvard Medical School, said that he and his colleagues created 20 stable iPS cell lines from patients with genetic diseases including Parkinson's, Huntington's, Down Syndrome, juvenile-onset Type I diabetes, and two types of muscular dystrophy.

Konrad A. Hochedlinger, a Medical School professor whose laboratory contributed the Lesch-Nyhan syndrome cell line to the project, said that the "iPS trick" will change the face of stem cell research.

Studying many diseases, especially degenerative diseases, often entails isolating cells that are not readily accessible, such as brain cells. But by deriving patient-specific iPS cells with the new technology, Hochedlinger said, researchers will be able to study the development of the disease in a lab dish.

Hochedlinger added that the iPS technology used in the research is still very new.

Two years ago, a group in Japan first reported that they had successfully reprogrammed mouse cells. And at the end of last year, research teams in Wisconsin and Japan and Daley's group all published the application of gene-based reprogramming of human cells.

"HSCI scientists have been among the first to practice iPS technology," Daley said. "And HSCI has by far produced the most human iPS lines to date."

The disease-specific iPS lines will soon be deposited in the new HSCI iPS Core Facility at Harvard-affiliated Mass. General Hospital to be produced at a larger scale for distribution among the scientific community.

The iPS Core Facility, which was established this July, is one of five core facilities at the Stem Cell Institute, including the Human Embryonic Stem Cell Facility at Children's Hospital, which is also a Harvard affiliate.

Laurence M. Daheron, who is the core facility manager, said that all iPS cell lines will be available free of charge for HSCI members and collaborators, but that non-members and biopharmaceutical companies will have to pay a fee to cover the cost of iPS lines expansion.

Daheron added that she hopes to start distribution for the cell lines created by Daley and his colleagues in the next few weeks.

Despite the potential for iPS cells to accelerate efforts to find treatments, both Hochedlinger and Daley stressed the continued importance of human embryonic stem cell research, which has come under fire from those who consider the destruction of embryos to be unethical.

Federal funding for embryonic research is currently constrained by a 2001 order by President Bush that limits funding for research on cell lines that existed at the time that he issued his directive.

The iPS cells are not subject to federal restrictions on embryonic stem cells as they are from skin cells or blood cells instead of embryos, a fact that allows iPS cells to sidestep much of the ethical debate surrounding research on embryonic stem cells. Hochedlinger said though that it would be a mistake to "give up on embryonic stem cells" before scientists find a way to make iPS cells without using potentially harmful genetic manipulation.

"For the foreseeable future, human embryonic stem cells will remain the gold standard," said Daley, whose research is currently funded by the National Institutes of Health, HSCI, and other private sources. "Even with iPS cells, we will want to study the biology of embryonic stem cell derivation, which occurs from embryos and won't be replicated by the iPS strategy.

—Staff writer June Q. Wu can be reached at junewu@fas.harvard.edu.