Lab-grown Nerves Promote Nerve Regeneration After Injury

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Lab-grown Nerves Promote Nerve Regeneration After Injury

http://www.sciencedaily.com/releases/2009/03/090319160122.htm

ScienceDaily (Mar. 20, 2009) — Researchers at the University of Pennsylvania

School of Medicine have engineered transplantable living nerve tissue that

encourages and guides regeneration in an animal model. Results were published in

March in the journal Tissue Engineering Part A.

About 300,000 Americans suffer peripheral nerve injuries every year, in many

cases resulting in permanent loss of motor function, sensory function, or both.

These injuries are a common consequence of trauma or surgery, but there are

insufficient means for repair, according to neurosurgeons. In particular,

surgeons need improved methods to coax nerve fibers known as axons to regrow

across major nerve injuries to reconnect healthy targets, for instance muscle or

skin.

" We have created a three-dimensional neural network, a living conduit in

culture, which can be transplanted en masse to an injury site, " explains senior

author H. , MD, Professor, Department of Neurosurgery and Director

of the Center for Brain Injury and Repair at Penn. and colleagues have

successfully grown, transplanted, and integrated axon bundles that act as

`jumper cables' to the host tissue in order to bridge a damaged section of

nerve.

Previously, and colleagues have " stretch-grown " 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.

These nerves were elongated to over 1 cm over seven days, after which they were

embedded in a protein matrix (with growth factors), rolled into a tube, and then

implanted to bridge a section of nerve that was removed in a rat.

" That creates what we call a `nervous-tissue construct', " says . " We have

designed a cylinder that looks similar to the longitudinal arrangement of the

nerve axon bundles before it was damaged. The long bundles of axons span two

populations of neurons, and these neurons can have axons growing in two

directions - toward each other and into the host tissue at each side. "

The constructs were transplanted to bridge an excised segment of the sciatic

nerve in rats. Up to 16 weeks post-transplantation, the constructs still had

their pre-transplant shape, with surviving transplanted neurons at the

extremities of the constructs spanned by tracts of axons.

Remarkably, the host axons appeared to use the transplanted axons as a living

scaffold to regenerate across the injury. The authors found host and graft axons

intertwined throughout the transplant region, suggesting a new form of

axon-mediated axonal regeneration. " Regenerating axons grew across the

transplant bridge and became totally intertwined with the transplanted axons, "

says

Axons throughout the transplant region showed extensive myelination, the fatty

layer surrounding axons. What's more, graft neurons had extended axons beyond

the margins of the transplanted region, penetrating deep into the host nerve.

Remarkably, the constructs survived and integrated without the use of

immunosuppressive drugs, challenging the conventional wisdom regarding immune

tolerance in the peripheral nervous system.

The researchers suspect that the living nerve-tissue construct encourages the

survival of the supporting cells left in the nerve sheath away from the injury

site. These are cells that further guide regeneration and provide the overall

structure of the nerve.

" This may be a new way to promote nerve regeneration where it may not have been

possible before, " says co-first author D. Kacy Cullen, PhD, a post doctoral

fellow in the lab. " It's a race against time - if nerve regeneration

happens too slowly, as may be the case for major injuries, the support cells in

the extremities can degenerate, blunting complete repair. Because our living

axonal constructs actually grow into the host nerve sheath, they may `babysit'

these support cells to give the host more time to regenerate. "

The other co-first author is Huang, MD, Assistant Professor of

Neurosurgery at Rochester University, who participated in the study during his

Neurosurgical residency at Penn.

This work was funded by the National Institutes of Neurological Disorders and

Stroke and the Sharpe Trust.