Harvard Scientists Create Safer Stem Cells

Researchers at the Harvard Stem Cell Institute are one step closer to achieving the ultimate promise of stem cell research—creating tissues for every part of the body—without the use of harmful viruses or cancer-causing genes.

Harvard Medical School professor Konrad A. Hochedlinger and his colleagues reported last week on the Web site of the journal Science that they have created mouse induced pluripotent stem (iPS) cells without permanently altering the genetic makeup of the cells.

The iPS 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.

Hochedlinger’s team inserted genes needed for cellular reprogramming with harmless adenoviruses.

Unlike retroviruses, which scientists have been using to create iPS cells, these viruses effectively disappear after a few cell divisions and do not integrate into the cells’ DNA. The effect of this is that adenoviruses are free from the chief adverse effect of genetic manipulation, which can turn on cancer genes and trigger malignant tumor growth.

“The beauty of this is that if you want to use the cells therapeutically—if you want to put them in somebody—it basically gets rid of the dangerous transcription factors that were used in the initial integration,” said Gordon C. Weir, a Medical School professor who heads the diabetes program at HSCI. “The last thing you want is to transplant a potentially malignant cell into a patient.”

The findings have implications for creating body tissues safe to transplant into patients to treat diseases.

The next step, according to lead author Matthias Stadtfeld, is to increase the efficiency of creating iPS mouse cells and then try to reproduce the work in human cells.

Currently, the number of iPS cells produced using retroviruses is significantly higher than that from the harmless adenoviruses. Stadtfeld, who is a post-doctoral research fellow at Harvard-affiliated Mass. General Hospital, estimated that using the more-dangerous retroviruses is 10 to 100 times more efficient than the new adenovirus method.

The recent advance in stem cell research is the latest in a stream of developments by Harvard researchers this past year.

At the third annual Stem Cell Summit held at the Medical School last week, University President Drew G. Faust cited four papers published this summer as evidence of the progress made at a time when federal funding for embryonic research has been constrained by a 2001 order by President Bush.

Among the discoveries were the creation of 10 disease-specific stem cell lines and the direct conversion of mouse pancreatic cells into insulin-producing beta cells that can be used to treat patients with Type I diabetes.

“At a time when the promise of biomedical research has never been greater, our nation risks sending a signal to our best and brightest young researchers that the funds won’t be there to support their hugely important career pursuits,” Faust said in her welcoming remarks.

And though the next presidential administration may prove friendlier to stem cell research, funding for the National Institutes of Health has been frozen in recent years, meaning that it has declined in real terms.

Though he used money from the NIH New Innovator Award that he won last year, Hochedlinger’s research was not subject to federal embryonic stem cell restrictions because iPS cells are created from skin cells or blood cells instead of from embryos. His work was also funded in part by the Harvard Stem Cell Institute.

While embryonic stem cell research has come under fire from those who consider it unethical, Harvard scientists involved in the work continue to say that the research is essential.

“As long as we don’t know that iPS cells are really as good as embryonic stem cells in generating all types of body tissues, we should be obliged to continue,” Stadtfeld said.

He noted that scientists are now able to generate iPS cells—which are embraced by those who oppose embryonic stem cell research—only because of previous work performed with embryonic stem cells.

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