MILWAUKEE — In a powerful demonstration of reprogramming’s potential to treat human disease and injury, scientists at the University of Wisconsin-Madison turned a rhesus monkey’s skin cells into early brain cells, then implanted them successfully in the monkey’s brain.
MILWAUKEE — In a powerful demonstration of reprogramming’s potential to treat human disease and injury, scientists at the University of Wisconsin-Madison turned a rhesus monkey’s skin cells into early brain cells, then implanted them successfully in the monkey’s brain.
The experiment, published Thursday in the journal Cell Reports, worked so well that the reprogrammed cells grafted onto the brain and appeared indistinguishable from the cells already there. Scientists were able to identify the new cells only because they had been tagged with a glowing green fluorescent protein.
Before being injected with their own cells, the three monkeys in the study were engineered to simulate the effects of Parkinson’s disease.
Although the experiment was carried out on monkeys, the results suggest that such an approach could work in humans, raising the possibility that doctors might someday replace the neurons lost to Parkinson’s or the cells damaged in spinal cord injuries.
“I think this is the first proof-of-principle demonstration that this personalized cell therapy may work,” said UW neuroscientist and stem cell researcher Su-Chun Zhang, who led the study. “We designed this experiment specifically for mimicking future therapies in patients. That’s why we used monkeys.”
Zhang said his lab is now using a grant from the National Institutes of Health to do long-term studies of monkeys that receive injections of reprogrammed cells to determine whether the cells help to improve symptoms. If the cell treatments prove beneficial, the next step would be to carry out clinical trials on human patients.
“I think it’s extremely significant,” said Eva L. Feldman, director of the Neuropathy Center at the University of Michigan. “I’m very excited about their paper and think it’s got a great deal of scientific potential and hope.”
Feldman, who was not involved in the UW experiments, said they mark an important moment in the discussion of what has been called personalized medicine — the idea that a patient’s own cells can be used to treat a broad spectrum of ailments. Such an approach would blunt the threat that a transplant might be rejected or send the immune system into battle.
Personalized medicine, Feldman said, “has been more of a theory to this point.”
The theory gained momentum with discoveries in 2006 and 2007 that showed scientists could rewind the developmental clock, turning a skin cell into the equivalent of an embryonic stem cell, but without the destruction of an embryo. This frees medical science to envision a day when patients’ blood, liver, brain and other cells may be banked and used to treat them when they suffer injury or disease.
The watershed of cell reprogramming was recognized last fall when the Nobel Prize in Medicine was awarded to Shinya Yamanaka of Japan and John B. Gurdon of England. But important work leading to the breakthrough came also from UW, where James Thomson became the first to isolate and grow human embryonic stem cells in 1998, then tied with Yamanaka in the race to reprogram human cells, achieving that landmark in 2007.
The UW study in rhesus monkeys now takes these advances and begins the long process of steering them toward medical practice.
Feldman said her lab has been taking skin biopsies from patients with amyotrophic lateral sclerosis, more commonly known as Lou Gehrig’s disease, and reprogramming those cells. In doing so, Feldman’s team can turn the skin cells into nerve cells to replace those destroyed by the disease. Similar experiments have been taking place all over the world, but most of the work has involved modeling and trying to treat diseases in a lab dish, not in an actual person.
Because of the physiological similarities between humans and monkeys, the UW experiment represents a significant step toward eventually attempting cell treatments in people with a host of ailments including heart disease, diabetes and Alzheimer’s.
“This is a very significant paper in the development of cell therapies for Parkinson’s disease,” said Ole Isacson, a professor of neurology at Harvard Medical School who was not involved in the study. Isacson added that the UW lab’s report demonstrates that reprogrammed cells from an “individual (primate) integrate well in the brain and could potentially restore function in a patient.”
Zhang said the reprogrammed cells were injected into two areas of the monkey brain, the basal ganglia and the midbrain. Both areas help to coordinate movement, but are damaged in Parkinson’s disease. This is why people with the disease shake and have difficulty with walking and coordination.
One of the most significant findings of the UW study was that scientists could not identify the point at which injected cells grafted onto the monkey brain. That indicated that the animal’s brain regarded the new cells as part of itself.
Zhang said the transplanted cells seamlessly forged connections and began functioning in the brain’s networks.