Mice got new vision and revived heart muscles and monkeys were able to flex muscles in paralyzed hands in research reported today that has extended the boundaries of regenerative medicine beyond the test tube.
In one study, night-blind mice implanted with precursor eye cells saw well enough afterwards to swim to a platform in dim light underwater. In another, heart cells in mice that had undergone heart attacks were converted to organ-pumping muscle. In a third, monkeys with arms that were paralyzed with nerve blocks were hooked to a computer that relayed signals from the brain to their hands, enabling them to grasp and move balls.
The reports in the journal Nature feature techniques that are part of research that may one day offer alternatives to those with bodies damaged by trauma or gene mutations.
“Cells in a dish is one challenge and, five to 10 years ago, that was exciting.” said Robin Ali, an author of the blind mice study, by telephone. “What’s interesting about these three papers is that we’re really starting to move into regenerative medicine. What these have in common is looking at repairing systems in vivo,” or in the whole, living organisms.
In the study by Ali, a molecular genetics professor at University College London, the mice with night blindness received precursors of rod cells, which function in less-intense light than other specialized cells called cones. Rods are almost entirely responsible for night vision. The transplanted cells formed synapses, improving night vision and enabling the animals to determine where a platform was in a dim water maze.
Color Blindness Next
The study may be a first step toward being able to repair all vision disorders, including color blindness, Ali said.
“Most causes of blindness are due to the loss of photoreceptors,” Ali said. “What I have in mind is approaching unrealistic -- I want to restore normal vision. But if we’re aiming to provide useful function, that may be achievable.”
In a second study, structural heart cells called fibroblasts were converted into cardiomyocytes, the cells that make the heart beat. These cells can’t function when damaged in heart failure and attacks, and until now, it was thought they couldn’t be repaired.
By dosing the cells of mice that had suffered heart attacks with three so-called transcription factors, researchers at the Gladstone Institute of Cardiovascular Disease were able to convert the structural cells into cardiomycytes and improve heart function. Transcription factors are regulatory proteins that bind to DNA in the body and help determine which genes are turned on and off.
‘Flipped the Switches’
“There are large pools of cells in the heart that aren’t muscle cells, and even though they aren’t meant to be muscle cells, if we flipped the switches, we thought we could convert it,” said Deepak Srivastava, director of the Gladstone Institute, located at the University of California, San Francisco, by telephone.
His group is now testing the method in pigs to see if it works in larger and more human-like animals.
Regenerative medicine uses biology, chemistry, engineering, robotics, genetics, medicine and computing to work around tissues and organs that fail. Previously, monkeys have controlled robot arms, while embryonic stem cells have been used in mice to form eye-like structures, new skin and cartilage.
Stem cells, though, are just one way of approaching the problems of degenerating bodies, Srivastava said. The appeal of the conversion factors is that changing existing cells is less traumatic than trying to implant stem cells, lowering the risk of cancer forming, he said.
“The field is reaching some maturity, and we’re seeing how this could be used down the road” in people, Srivastava said. “We’ve been working very hard the last several years, working things out in a dish. We’ve matured now to a point where we can make improvements in a whole organism, a step toward people.”
The final study, by Lee Miller, a professor of physiology at Northwestern University’s Feinberg School of Medicine in Chicago, used two monkeys that had nerve blocks designed to simulate paralysis like that in patients with spinal cord injuries. Unlike a previous study, in which monkeys moved robot arms using signals relayed by a computer, Miller’s technique used an electrical device to stimulate the monkeys’ own arm muscles.
Eventually, both monkeys used their paralyzed hands to pick up and move balls, according to the report.
“In our lab, we’re beginning to work on the technology necessary to move from one or two hours a day in the lab to something that would work over 24 hours,” Miller said in a telephone interview.
Questions remain about using the technology for real spinal cord injuries in people, Miller said.
For instance, those who permanently stop getting signals from the nerves in their legs or arms have shown corresponding changes in their brains. In the future, researchers will study whether use of techniques including stimulation devices will restore the brain’s original patterns, Miller said.
The studies were funded by the Medical Research Council UK, the Wellcome Trust, the National Institutes of Health in Bethesda, Maryland, and others. Srivastava was also supported by a grant from the Roddenberry Foundation, created by Star Trek creator Gene Roddenberry’s son to “turn science fiction into science fact,” according to its website.
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