Stem cell researcher Kevin Eggan,
(third from left,bottom row)
with members of his lab at Harvard,
from his website.
By Elie Dolgin
Milwaukee Journal Sentinel (MCT)
MILWAUKEE — Researchers are one step closer to reprogramming skin cells into tailor-made, healthy replacements for diseased cells.
Applying the technique first developed by James Thomson of the University of Wisconsin-Madison and Shinya Yamanaka of Kyoto University, scientists at Harvard and Columbia universities reported online Thursday in the journal Science that they had turned skin cells from two elderly patients with the neurodegenerative disorder amyotrophic lateral sclerosis into motor neurons, the nerve cells that become damaged in ALS.
This is the first time that scientists have coaxed embryonic-like cells from adult patients suffering from a genetic-based disease, then induced the cells to form the specific cell types that would be needed to study and treat the disease.
"It's a big step forward," said Stephen Duncan, a stem cell researcher at the Medical College of Wisconsin in Wauwatosa, who was not involved in the research. "It opens the door for people to go confidently into generating (reprogrammed stem) cells for other disease models."
"We're on the threshold of a new era of technology ... where we might have some definitive strategies to better treat or cure diseases like ALS or other neurodegenerative diseases," said Medical College neurologist Paul Barkhaus.
A team led by Kevin Eggan of the Harvard Stem Cell Institute in Boston started with skin cells from two sisters, ages 82 and 89, who both carried a rare gene associated with a slowly progressing form of ALS, also known as Lou Gehrig's disease.
Around the world, one or two people per 100,000 develop ALS each year, which is marked by a wasting away of certain spinal cord nerve cells called motor neurons. The single-gene form of ALS studied by Eggan's team affects only about 2 percent of ALS sufferers, while the vast majority of ALS cases are sporadic.
In their laboratory, the researchers inserted four genes into the cells using a virus — just as Thomson and Yamanaka had done last November — that rewound the cell's developmental clock into an embryonic-like state.
The researchers then bathed the cells in signaling molecules to produce motor neurons and the nerve cells that support and protect the neurons, called glial cells.
"It's possible to use these cells to make the actual cell type that is destroyed in that person's disease," Eggan said. "It takes the study of disease out of the patient, where it's very difficult, and into the Petri dish."
The researchers' ultimate goal is to create genetically matched, patient-specific cells to treat debilitating diseases. But the current technique of inserting genes with viruses has potential cancerous side effects, making transplanting these cells into humans too risky.
"The process leads to genetic modification of these cells," Eggan said. "For the moment, that would preclude the use of these exact cells in these patients."
Future research should find safer reprogramming methods, scientists say. In the meantime, the new reprogrammed stem cells will be valuable for understanding and combating the damage ALS does to the nervous system.
"These patient-specific stem cells will be useful for pathological studies, and potentially also for drug screening," said UW-Madison stem cell researcher Su-Chun Zhang, who was not involved in the study.
"Using these cells, we can test chemical compounds for their ability to prevent (neuron) degeneration," said Christopher Henderson, a neurologist at Columbia University, and a co-author of the study.
UW-Madison's Junying Yu, the first author on Thomson's pioneering reprogramming study, published last year, said the new research is a natural extension of their earlier "proof of principle" work.
"It essentially proves that (reprogrammed stem) cells can be derived from diseased human (skin) cells as well" as from healthy patients, "at whatever age, young people or old people."
Yu said her lab also reprogrammed skin cells from patients suffering from spinal muscular atrophy, a neurodegenerative disease that controls voluntary muscle movement. Like Eggan's group, she said her team then successfully formed the muscle cells normally lost by the disease, although the work is not yet published.
Eggan's study shows that specialized cells can be made from skin cells in the lab, but the researchers didn't test whether the cells function in the same way as normal motor neurons, noted UW-Madison stem cell researcher Clive Svendsen.
"The hard work now is to establish whether the ALS (reprogrammed) cells are any different from those taken from normal patients."
Because reprogrammed stem cells can trigger cancer, scientists stress that research involving human embryonic stem cells is still needed.
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