A complex combination of treatments, including stem cells and growth factors, can heal damaged neural circuits, allowing partially paralyzed rats to walk. These findings represent a significant step forward in regenerative medicine, providing new treatment possibilities for Amyotrophic Lateral Sclerosis (ALS) and other neurodegenerative diseases, as well as some types of spinal-cord injury.
“This work is a major stepping-stone to human application of stem-cell transplant approaches,” says Hans S. Keirstead, co-director of the Stem Cell Research Center at the University of California, Irvine. He says that the ability to grow new neural fibers out of the spinal cord “renders transplantation approaches to repair realistic.”
Previous research has shown that cell transplants and other treatments can help paralyzed rodents walk. But those experiments have focused mainly on repairing local damage within the spinal cord. They could help patients whose motor neurons – cells carrying messages from brain to spinal cord – remain intact after injury or disease.
In contrast, the current study, conducted by a team of scientists at Johns Hopkins University, focused on a longer-distance repair problem. It is the first study to show that newly grown nerve fibers can emerge from the spinal cord, extend all the way to the muscle, then form functional connections with muscle. This feat is particularly important for ALS and other disorders characterized by the loss of motor neurons. “Some may have thought this was a bridge you can’t cross,” says David Owens, research director at the National Institutes of Neurological Disorders and Stroke, which sponsored the study.
[Click here to see a brief video of a rat that has been partially paralyzed by a virus. Then click here to see the same rat four months after receiving the full “recipe” of embryonic stem cells, as well as growth factors for overcoming myelin inhibition and growth factors released from neural stems cells.]
Researchers caution that the work is just a first step, and that human trials are likely several years away. Indeed, the findings highlight just how complex spinal injuries and neurodegenerative disorders are and how complicated successful treatments are likely to be.
The spinal cord is a precisely organized neural circuit, with one set of neurons connecting the brain to the spinal cord and another set joining the spinal cord to muscles. The nervous system has evolved several mechanisms to maintain the circuit’s tight structure – and that strict regulation presents a serious obstacle for scientists who want to rewire the system after damage or disease.
To overcome these hurdles, Douglas Kerr and his team at Johns Hopkins took clues from the developing nervous system. “In the developing nervous system, there are signposts along the way that tell every cell and every wire where to go and what to do,” says Kerr.
The researchers first took embryonic stem cells and transformed them in a dish into motor neurons. They then transplanted the cells into the spinal cord, along with a mix of growth factors normally present during development, to help the new cells survive and to encourage surrounding cells to make connections with the transplanted ones. The scientists also added two chemicals known to overcome the inhibitory forces that normally keep nerve fibers from growing out of the spinal cord.