Using iPs cells to create disease models

While much of the public discussion and debate concerning stem cell research has focused on the possibility of developing stem cell therapies for a myriad of chronic, often fatal diseases, scientists have been equally excited by the potential that stem biology offers to study human diseases in the laboratory.

This past summer, and again just in the past month, HSCI scientists began to fulfill that promise by producing more than 20 stem cell lines from patients with diseases ranging from diabetes to Parkinson’s, and also by using stem cells to produce “industrial strength” quantities of the cell type destroyed in patients suffering from Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disease.

In August, HSCI Executive Committee member George Daley, MD, PhD, announced that he and HSCI colleagues Chad Cowan, PhD, and Konrad Hochedlinger, PhD, had produced 20 disease-specific stem cell lines. Using the new induced pluripotent stem cell (iPS) technique, HSCI researchers derived the cell lines from the adult cells of patients suffering from, among other conditions, Parkinson’s Disease, Type I diabetes, Huntington’s Disease, Down Syndrome, a form of combined immunodeficiency (“Bubble Boy’s Disease”), Lesch-Nyhan syndrome, Gaucher’s Disease, and two forms of Muscular Dystrophy.

“We wanted to produce a large number of disease models for ourselves, our collaborators, and the stem cell research community to accelerate research,” Daley said. “The original embryonic stem cell lines are generic and allow you to ask only basic questions. 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,” he said.

The disease-specific iPS cells are part of the first “deposit” at the new HSCI iPS core facility, which will make the new cell lines available to researchers worldwide at a nominal fee to cover costs. The facility, established at Massachusetts General Hospital, will not only serve as a repository for iPS cells produced by HSCI scientists but also function as a technical laboratory to produce these disease-specific lines.

“The suite of iPS cell lines reported by the Daley group marks an important achievement and a very significant advance for patients suffering from degenerative diseases,” said Douglas Melton, PhD, Co-Director of HSCI. “These disease-specific iPS cells are invaluable tools that will allow researchers to watch the development of diseases in petri dishes, outside of the patients. And 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. In years ahead, this report will be seen as opening the door to a new approach to develop therapies.

” Daley and his colleagues intentionally produced some stem cell lines for highly heritable, single-gene diseases, such as Gaucher’s; complex genetic syndromes, such as Down Syndrome; and complex diseases that involve genetic, cellular, and perhaps environmental components, such as Parkinson’s. “The cell lines available from the iPS core will allow stem cell researchers around the world to explore possible gene therapies for some conditions and will aid in the development of drugs for others,” Daley said.

Shortly before the work of Daley and his collaborators was announced, HSCI Principal Faculty member Kevin Eggan, PhD, and colleagues used iPS technology to produce human stem cell lines from patients suffering from ALS and coax from them the motor neurons destroyed by the disease process. Harvard Provost Steven Hyman, MD, himself a neurobiologist, called the feat an “important step in fulfilling the promise of regenerative medicine. It is yet more confirmation that the substantial risks that were taken in forming the Harvard Stem Cell Institute will ultimately pay off for both science and patients.”

“No one has ever managed to isolate these neurons from a patient and grow them in a dish,” Eggan said. “Now we can make limitless supplies of the cells that die in this awful disease. This will allow us to study these neurons and ALS in a lab dish and figure out what’s happening in the disease process.”

Eggan’s work was recently listed as TIME magazine’s top medical breakthrough in 2008.