The Biggest Step:
Study Shows New Motor Neurons Cross the Cord

A Campenot chamber looks like a racetrack for cells, a hollow ring you can put under a microscope. Center researcher Doug Kerr uses one with sliding doors—slips of glass he can pull back so whatever’s in one arm of the ring can contact what’s in the other. During this past year, Kerr has watched as two separate sets of cells, stem cell-derived motor neurons and muscle cells, interact in a rather lovely way to stir hope of restoring function in motor neuron disease.

A quick check of tell tale proteins tell Kerr he's got motor neurons.

Already Kerr has used his system—which tells how muscle and nerve encourage each other to connect—to show that a stem cell approach in animals makes sense. Recently, he’s found that stem cells with motor neuron leanings begin to grow in the right places when injected into spinal cords of injured rats.

Normally, motor neurons developing in utero send their axons to muscle, forming a right relationship, a synapse, with it. Then muscle contractions follow. Kerr knew his preliminary studies had to show all of that could happen.

So his team began by coaxing mouse embryonic stem (ES) cells, via cell growth agents, to become motor neurons. They placed neurons in the Campenot chamber within hailing distance of young muscle cells. “The moment we raised the divider,” Kerr says, “the motor neurons started to change.” So did the muscle cells. Both produced signaling molecules like agrin, an “advanced scout” that readies both nerve cells and target muscles for docking. Within three hours, axons poked outward from the motor cells, extending toward the muscle cells.

Before long, proper synapses appeared. And to Kerr’s delight, neuron-connected muscle cells started to twitch.

Satisfied, Kerr moved to rats. He injected about 12,000 of the ES-based motor cells directly into the animals’ spinal cords. Roughly 4,000 of the cells survived—putting one worry to rest. “They looked gorgeous,” Kerr says. Trouble was, however, their axons wouldn’t cross the spinal cord.

Center scientist Marie Filbin and others told Kerr that myelin, the nerve cell insulating material, potently inhibits axon growth. And spinal cords are ringed by myelinated neurons! Filbin, however, had uncovered agents that reverse myelin’s action. And after implanting the rats with a pump to drip the agents near the animals’ spinal cords, Kerr saw motor neurons extend through the cord to a key motor neuron way station on the other side—they’d jumped a major hurdle.

Though only 90 cells made it through, Kerr’s an optimist. Now he’s exploring ways to lure axons to muscle targets, as happened in the lab dishes. “We’ll never restore the original complexity of the motor system,” he says. “But to regain useful function, we may not need to put everything back. A few connections could make a real difference.”

Next > Laurie Russell Helps Scientists See a Bigger Picture
At a recent reception held in her honor at Johns Hopkins’ new Broadway Research Building, guests were invited to see the fruits of her labor—a novel confocal microscope Russell, her close friends and family purchased for the Center.