Penn researchers engineer first system of human nerve-cell tissue

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Penn researchers engineer first system of human nerve-cell tissue

Implications for nerve repair and implantation

http://www.eurekalert.org/pub_releases/2008-02/uops-pre022608.php

Researchers at the University of Pennsylvania School of Medicine have

demonstrated that living human nerve cells can be engineered into a

network that could one day be used for transplants to repair damaged

to the nervous system. They report their findings in the February

issue of the Journal of Neurosurgery.

" We have created a three-dimensional neural network, a mini nervous

system in culture, which can be transplanted en masse, " explains

senior author H. , MD, Professor, Department of

Neurosurgery and Director of the Center for Brain Injury and Repair

at Penn.

Although neuron transplantation to repair the nervous system has

shown promise in animal models, there are few sources of viable

neurons for use in the clinic and insufficient approaches to bridge

extensive nerve damage in patients.

The Stretch Test In previous work, 's group showed that they

could induce tracts of nerve fibers called axons to grow in response

to mechanical tension. They placed 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, creating long tracts of living

axons.

These cultures were then embedded in a collagen matrix, rolled into a

form resembling a jelly roll, and then implanted into a rat model of

spinal cord injury. 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 extended through the

collagen barrier to connect with the host tissue as a sort of nervous

tissue bridge.

The Next Step

Now, the researchers have taken the next step and are applying this

technique to living human nerve cells. and his team obtained

human dorsal root ganglia neurons (due to their robustness in

culture) to engineer into transplantable nervous tissue.

The root ganglia neurons were harvested from 16 live patients

following elective ganglionectomies, and four thoracic neurons were

harvested from organ donors. The neurons were purified and placed in

a specially designed growth chamber. Using the stretch growth

technique, the axons were slowly pulled in opposite directions over a

series of days until they reached a desired length.

The neurons survived at least three months in culture while

maintaining the ability to generate action potentials, the electrical

signals transmitted along nerve fibers. The axons grew at about 1

millimeter per day to a length of 1 centimeter, creating the first

engineered living human nervous tissue constructs.

" This study demonstrates the promise of adult neurons as an

alternative transplant material due to their availability, viability,

and capacity to be engineered, " says . " We've also shown the

feasibility of obtaining neurons from living patients as a source of

neurons for autologous, or self, transplant as well as from organ

donors for allografts. "

Penn co-authors are H. Huang, L. Zager, Jun Zhang,

G. Groff IV, J. Pfister, M. Grady, and Eileen Maloney-

Wilensky. Akiva S. Cohen from The Children's' Hospital of

Philadelphia was also a co-author.

The authors thank the Gift of Life program and the family members of

the organ donors for their support and selfless sacrifice. This work

was funded by the National Institutes of Health.