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March 21, 2009

Lab-Grown Nerves Promote Nerve Regeneration After Injury, Penn Study Finds


A surviving cluster of transplanted neurons at the graft extremity (top) with axons in the center (bottom). In both images, transplanted nerve cells are labeled green and axons are stained red. These axons are a mix of the transplanted axons and host axons, which intertwined as regeneration occurred directly across the transplanted tissue.

– Researchers at the University of Pennsylvania School of Medicine have engineered transplantable living nerve tissue that encourages and guides regeneration in an animal model.

“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 Douglas H. Smith, MD, Professor, Department of Neurosurgery and Director of the Center for Brain Injury and Repair at Penn. Smith 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.

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 Smith. “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.http://www.blogger.com/post-create.g?blogID=17555522

Remarkably, the host axons appeared to use the transplanted axons as a living scaffold to regenerate across the injury.







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 Smith 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.”


FURTHER READING
Journal of Tissue Engineering (which has the article)

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