Stem cell summit hails bench progress, looks to bedside future

5 min read

New discoveries concerning cell reprogramming over the past year have boosted stem cell researchers in the lab and encouraged efforts to transfer test tube and lab animal advances to humans suffering degenerative diseases such as diabetes, Parkinson’s disease, and Lou Gehrig’s disease.

Leaders of the Harvard Stem Cell Institute (HSCI) and Harvard President Drew Faust hailed advances in the last year as significant steps in the drive to understand and one day treat these diseases, which afflict millions around the world.

Among the advances they cited are a treatment that cured a form of muscular dystrophy in mice, the production of stem cell lines from patients suffering 10 different diseases, the creation of nerve cells from patients suffering Lou Gehrig’s disease, and the direct conversion of mouse pancreatic cells into the insulin-producing beta cells destroyed in diabetes.

The comments were made Monday (Sept. 22) at the third annual Stem Cell Summit, sponsored by the Harvard Stem Cell Institute and held at Harvard Medical School. In her welcoming remarks, Faust singled out the four new findings by HSCI researchers as evidence that real progress is being made.

“If discoveries like these were emerging at a rate of one a year, we would have good cause to celebrate. It is a tribute to the work of the institute that all four of the papers I just mentioned were published this last summer alone,” Faust said. “Everything I know about your work and the work of this institute makes me feel that we really do live in historic times — something people will look back on years from now and see as a watershed in our understanding of human biology and in our capacity to seek treatments and cures for a myriad of diseases.”

Faust praised not just the “remarkable progress” made since the HSCI began in 2004, but also the fact that major advances were made despite the federal government’s refusal to fund a significant part of the work.

“This may well be the first time since the end of World War II when major progress in basic biomedical science in the U.S. has been enabled primarily by farsighted private individuals, foundations, and institutions rather than by the federal government,” Faust said.

She warned that even with a change in the nation’s leadership coming, stem cell researchers shouldn’t expect a large influx of federal dollars. Though the next presidential administration may be friendlier to stem cell research, funding through the National Institutes of Health has declined in recent years. That means stem cell researchers will have to compete with scientists in other fields for a declining pot of federal dollars.

“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.

Harvard Stem Cell Institute Co-Director David Scadden, the Jordan Professor of Medicine at Harvard Medical School and Massachusetts General Hospital, said the past year has been “extraordinary” for stem cell science. He hailed advances at Harvard and elsewhere that “exploded” the previous view that cellular development from embryonic to differentiated adult tissues is a one-way street.

In several different instances, researchers have discovered ways to turn back the clock and reprogram cells into those crucial to understanding and one day treating disease. Scadden said the Stem Cell Institute is beginning to build a library of cell types involved in disease — nerve cells from patients with Lou Gehrig’s disease, for example — that researchers can use in their studies.

“That process of reprogramming is an extraordinarily powerful tool in the hands of researchers,” Scadden said. “This is just the beginning.”

Despite the encouraging progress, however, much work remains to be done. Some of the transcription factors used in cellular reprogramming can lead to cancer, making that process — useful in creating cells for research — unsuitable to treat patients. The search is on, he said, for chemicals that can mimic the transcription factors’ effects without potentially dangerous side effects.

During the summit’s daylong event, speakers detailed progress in specific disease areas, including cancer, the nervous system, and the cardiovascular system, and discussed other topics such as the outlook for state and federal government policy, clinical trials for therapy, drug discovery, and commercialization of research advances.

Harvard Stem Cell Institute Co-Director Douglas Melton, Cabot Professor of the Natural Sciences, detailed recent work on diabetes, including his success directly converting one type of pancreatic cell into another. The advance holds the promise of allowing researchers to create a supply of tissues needed for study or therapy without having to go through the many-step process of changing adult cells back into embryonic-like stem cells and then re-differentiating them to the needed cell type.

In that work, Melton and colleagues took pancreatic exocrine cells, which produce digestive enzymes that are released into the gut, and used three transcription factors to convert them directly into insulin-producing beta cells.

“It opens the possibility of converting cells — at least within the same cell lineage — into a useful cell,” Melton said. “We think this provides another weapon in our arsenal to make cells that are deficient.”

Melton also said researchers made advances in learning how to replicate beta cells from existing beta cells and are making progress in efforts to get embryonic stem cells to differentiate into beta cells. In that case, he said, researchers have mastered two steps in what they believe will be a six- or seven-step process.

“We won’t solve all the steps in the next year, but we believe this is a solvable problem,” Melton said.