Personalized Stem Cells One Step Closer to Reality

July 31, 2008— -- For the first time, scientists have proven that embryonic-like stem cells that are specific to both a person and to a disease can be manufactured using adult human cells.

Personalized stem cells may be the holy grail of science because of their potential to treat and allow the study of a myriad of diseases and conditions. And while there are still a number of hurdles to clear before this advance can be applied to humans, in the clinical setting this latest step, some say, shows promise of eventual human therapies.

Researchers from Harvard and Columbia Universities used skin cells from two patients with Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, to create stem cells and then reprogrammed them to morph into replacement motor neurons.

"It opens doors to making patient-specific stem cell lines," said Dr. Kevin Eggan, principle faculty member at the Harvard Stem Cell Institute and lead author of a study that was released today in the journal Science. "You can use these cells to make the actual cell type for that person's disease."

People with ALS experience progressive degeneration in their motor neurons to the extent that the brain and spinal cord can no longer signal the body to move. Patients in later stages of the disease often become paralyzed.

Eggan and his colleague, Dr. Christopher Henderson, co-director of the Center for Motor Neuron Biology and Disease at Columbia University and the other lead author, stressed that their study shows "proof of principle" for how embryonic-like stem cells can be created from adult cells using induced pluripotent stem (iPS) cells, a technique introduced widely last year.

Stem cell researchers not involved in the study called the advance promising.

"The hope for iPS cell technology is that you could create cells from your own body to treat your own defects," said Dr. Curt Freed, professor of medicine and pharmacology at the University of Colorado School of Medicine. "They are immunologically matched to yours."

But Freed pointed out that iPS derived stem cells will never be used for therapeutic purposes because the method requires using retroviral genes to copy the cells -- genes which result in cancer-producing cells.

A New Approach

The ideal scenario for stem cells would be to create them by injecting the desired DNA -- DNA that's free from genetic defects -- into human egg cells and letting them become stem cells before reprogramming them into specific cell types, a technique known as somatic cell nuclear transfer (SCNT). But getting human egg donations -- as well as funding for such research -- has been difficult for the researchers.

"The inability to have success with SCNT is wrapped up in logistical and political quagmires," Eggan said.

At the moment, the next step for this study is to determine how similar and different the new motor neurons from the iPS derived stem cells are from human motor neurons.

"We have the opportunity to study these motor neurons and see whether they behave in a manner that they do in the culture dish," Henderson said. "Although the promise of these ideas are there, there is much validation to do in terms of their potential to generate different types of neurons.... The [SCNT] embryonic stem cell model is really our gold standard."

But the discovery that only a few genes are necessary to nudge a human stem cell to develop into a specialized adult cell is encouraging. The finding also underscores the theory that almost any cell of any age in the body can be reprogrammed into any other type of cell, given the right genetic expression.

"It gets us closer to when we are able to use chemicals alone," Eggan said.

Not Ready for Clinical Setting... Yet

Rather than be used for therapy right now, Eggan and Henderson said that the cells they created will be most useful to study the nature and pathology of the disease, particularly in terms of determining what drugs might be effective to treat it.

"Studies... suggest that things are going wrong in those individuals far, far, far before they're ever outwardly sick," Eggan said, referring to a potentially fundamental difference between diseased neurons and normal neurons. "And it's those molecular correlates of disease which will be our first inroads into better understanding of the disease and then, in turn, treatment."