Scientists have used stem cells and a soup of nerve-friendly chemicals to not just bridge a damaged spinal cord but actually regrow the circuitry needed to move a muscle, helping partially paralyzed rats walk.
Years of additional research is needed before such an experiment could be attempted in people.
But the work marks a tantalizing new step in stem cell research that promises to one day help repair damage from nerve-destroying illnesses such as Lou Gehrig’s disease, or from spinal cord injuries.
“This is an important first step, but it really is a first step, a proof of principle that ... you can rewire part of the nervous system,” said Dr. Douglas Kerr, a neurologist at Johns Hopkins University who led the work being published Monday in the journal Annals of Neurology.
Perhaps most importantly, the experiment illustrates that if stem cells eventually live up to their promise, treatment won’t be simple — they can’t just be injected into a diseased body and repair it on their own.
A complex recipe
Instead, the new research details a complex recipe of growth factors and other chemicals that entice the delicate cells to form correctly and make the right connections. Miss a single ingredient, and the cells wander aimlessly, unable to reach the muscle and make it move.
The study may bring “the appropriate tempering of expectations of stem cells,” said Kerr, considered a leader in the field. “Some of my patients say, 'Oh, I’m going to pull into the stem-cell station and get my infusion of stem cells,’ and it’s never going to be that.”
Stem cells are building blocks that turn into different types of tissue. Embryonic stem cells in particular have made headlines, as scientists attempt to harness them to regenerate damaged organs or other body parts. They’re essentially a blank slate, able to turn into any tissue given the right biochemical instructions. But human embryonic stem cell research is politically controversial, because culling the cells destroys embryos.
Installing 'new wiring'
The Hopkins experiment isn’t the first to use stem cells to help paralyzed rodents move. But previous work bridged damage inside the spinal cord that blocked nerve cells from delivering their “move” messages to muscles, sort of like fixing the circuit that brings electricity to a fan.
The new work essentially installs new wiring: replacing motor neurons — specialized nerve cells for movement — that have died to make a new circuit that grows neuronal connections out of the spinal cord and down to a leg muscle.
“They did something that people have been trying to do for at least 30 years and literally hit a brick wall until now,” said Dr. Naomi Keitman of the National Institutes of Health’s neurology division, which partly funded the work along with patient advocacy groups.
First, Kerr mixed embryonic stem cells from mice with chemicals that caused them to turn into motor neurons. He transplanted them into the spinal cords of partially paralyzed rats.
Some rats received neurons treated with substances to boost their survival chances.
Even if the fledgling motor neurons lived, insulation called myelin on surrounding nerve cells would inhibit their growth. So some rats also received injections of chemicals, including an antidepressant called rolipram, thought to neutralize myelin’s antigrowth effect.
Still others were injected with a growth factor called GDNF near the leg muscle, as a signpost to direct the new neurons to form connections there.
Only the group of rats that got every extra ingredient improved, Kerr found. The paralysis wasn’t completely gone, but six months after treatment, 11 of the 15 animals could bear weight, take steps and push away with the affected leg.
Of the roughly 4,000 new motor neurons generated in the rats’ spinal cords, about 120 reached the muscle, and 50 were electrically active, further testing showed.
The next step, to start this summer: Redoing the experiment in pigs, to see if new neurons can be enticed to grow connections over the longer distances needed to reach from a pig’s spinal cord to its leg.
