16 February 2006

Nerve Constructs Grown in Lab for Spinal Cord Repair

This newsrelease from eurekalert.org reports on a new technique for growing "jumper wire" neuron constructs, for repairing disruptions in nerves--hopefully CNS nerve networks in the spinal cord--and possibly brain. The research was done at UPenn School of Medicine.

"We have created a three-dimensional neural network, a mini nervous system in culture, which can be transplanted en masse," explains senior author Douglas H. Smith, MD, Professor, Department of Neurosurgery and Director of the Center for Brain Injury and Repair at Penn. Previously, Smith's group showed that they could grow axons by placing neurons from rat dorsal root ganglia (clusters of nerves just outside the spinal cord) on nutrient-filled plastic plates. Axons sprouted from the neurons on each plate and connected with neurons on the other plate. The plates were then slowly pulled apart over a series of days, aided by a precise computer-controlled motor system.

In this study, the neurons were elongated to 10mm over seven days – after which they were embedded in a collagen matrix (with growth factors), rolled into a form resembling a jelly roll, and then implanted into a rat model of spinal cord injury.

...."That creates what we call a nervous-tissue construct," says Smith. "We have designed a geometrical arrangement that looks similar to the longitudinal arrangement that the spinal cord had before it was damaged. The long bundles of axons span two populations of neurons, and these neuron constructs can grow axons in two directions – toward each other and into the host spinal cord at each side. That way they can integrate and connect the 'cables' to the host tissue in order to bridge a spinal cord lesion."

After the four-week study period, the researchers found that the geometry of the construct was maintained and that the neurons at both ends and all the axons spanning these neurons survived transplantation. More importantly, the axons at the ends of the construct adjacent to the host tissue did extend through the collagen barrier, penetrating into the host tissue. Future studies will measure neuronal electrical conductivity across the newly engineered bridge and restoration of motor activity.

Obviously there is a lot of work that has to be done before this procedure is ready for human trials. To get these dorsal root ganglia neurons to grow inside the spinal cord, to reconnect severed nerve pathways, will likely require a lot more knowledge of growth factors, stem cell integration in nerve constructs, cell adhesion factors, etc. Still, the foundational work has to be done before the upper structures can be erected.

A lot of people with spinal cord damage will feel they cannot wait for this line of research to pan out, and some will go to clinics that will inject embryonic stem cells into their spinal cords--in Russia and elsewhere. That procedure will amount to human experimentation at the patient's considerable expense, but people will grasp for hope wherever it can be found. Perhaps they will get lucky and succeed in "jumping the queue". I hope so. Until we know if there are any shortcuts, the slogging in the trenches with animal models must go on, with each advance documented and verified.
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