Harvard, Columbia Researchers Make Stem Cell Breakthrough

Scientists from Harvard and Columbia announced Thursday the creation of the first patient-specific stem cell line from humans afflicted with a genetic disease, a key step in the push to create therapies for a wide variety of illnesses by replacing diseased tissue with tissue generated by stem cells.

The study's two principal authors said in a press conference Wednesday that such treatments remained years away and that the more immediate impact of the disease-specific stem cells will be the ability to study disease progression and test potential treatments in a lab setting.

"We now have in the culture dish cells which have the same genetic makeup as do the ALS patients, and they are the very cells that are affected by the disease." said Columbia professor Christopher Henderson, referring to Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative often called Lou Gehrig's Disease. "This provides us with the opportunity...to study these motor neurons derived from the ALS cells."

The study, which was co-authored by Henderson and Harvard professor Kevin C. Eggan, was published Thursday in the journal Science.

The age of the cell donors—82 and 89—gave the findings added significance, as some scientists had predicted using cells from older patients would complicate the creation of stem lines, according to Eggan.

"This opens the door to being able to make patient-specific, stem cell lines from diseases which affect people very late in life like Parkinson's disease or Alzheimer's disease," Eggan said.

Though the researchers originally planned to produce disease and patient-specific stem cells using the controversial practice of therapeutic cloning, which requires both a supply of human egg cells and the destruction embryos created to produce the stem cell lines, they opted instead to use a newer technique called "direct reprogramming," which was first unveiled late last year.

This method takes regular human cells—in this case skin cells—and uses viruses to reprogram them into cells that can develop into any kind of human tissue, in theory providing all the benefits of embryonic stem cells.

The current reliance on viruses renders the stem cell lines unsafe for transplantation because the process genetically modifies the reprogrammed cells. But Eggan predicted that researchers would soon fix this shortcoming with a process that instead uses chemicals to reprogram cells.

"Future research is surely going to focus on ways to replace those viruses with chemicals," he said. "And I think we'll see that in a short amount of time."

Both scientists repeatedly said that research on therapeutic cloning should not be abandoned, in large part because they said it was necessary to test the utility of reprogrammed cells against an embryonic stem cell bench mark.

"We need to compare these cells we've generated to the gold-standard cells we've generated from human embryonic stem cells," Eggan said. "Until we can do that, we won't have complete confidence."

Despite their insistence, the breakthrough and continuing difficulty in getting the egg cells required for therapeutic cloning suggests that reprogramming may provide greater hope for stem cell therapies.

Eggan said that Massachusetts law prohibiting compensation of human egg donors had stymied his lab's efforts to study the disease.

"We've now spent roughly $100,000 on advertising," Eggan said. "We've only had one woman follow through and go through the considerable effort of donating oocytes [egg cells] for research. I would characterize the number of oocytes she donated as a handful. And the results we had from those very few initial experiments were encouraging, but there's no sign of additional donors in sight."

Though the researchers expressed optimism about their ability to use the reprogrammed stem cells to study the progression of Lou Gehrig's disease and test potential treatments, a number of hurdles remain to discovering such therapies.

The researchers have not yet shown that the stem-cells-derived neurons degenerate as diseased neurons do in the human body, but they added they hope to do so in a matter of months.

In addition, the stem cells are specific to only a certain type of the disease, which afflicts less than five percent of sufferers, Eggan said. But the study authors said research on this less-common variant could have broader applications, if, as they hope, the disease mechanism is similar for most or all types of Lou Gehrig's disease despite different initial triggers in the vast majority of ALS patients.

"Our real hope is that very similar events are occurring in these sporadic patients--the 90 percent of patients in which the trigger is different," Henderson said. "Since the diseases are so similar we believe that many of the mechanisms must be similar or the same."

—Staff writer Clifford M. Marks can be reached at cmarks@fas.harvard.edu.