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Clonal human neurons re-establish connection in rats with severe spinal cord injury, USF study finds


Human neurons grown as cells cloned from a tumor helped restore the function of severely injured spinal cords in rats, University of South Florida researchers say in a study released this week in the Journal of Neurosurgery: Spine.

"Transplants of these specially treated cells were used to patch a short circuit in the spinal cord of rats," said Samuel Saporta, PhD, associate director of the USF Center for Aging and Brain Repair, professor of anatomy and lead author of the study. "We demonstrated the cells are safe, survive and can electrically reconnect the undamaged parts of the spinal cord."

A couple of the spinal cord-injured (SCI) rats could bear weight on their hind legs following transplantation with the experimental cells, known commercially as hNT, or LBS, neurons. However, the researchers emphasize, more studies are needed to determine if rats with reconnected spinal cords can walk again.

"We are hopeful that our work with hNT neurons in an animal model for spinal cord injury will ultimately lead to the first transplant of human neural progenitor cells to treat spinal cord injury in humans," said neuroscientist Paul R. Sanberg, PhD, DSc, director of the USF Center for Aging and Brain Repair and a study co-author.

Dr. Saporta, Dr. Sanberg and colleagues at USF conducted preclinical research with hNT neurons that led to the first transplant to repair brain damage from stroke in 1998. That clinical trial, ongoing at the University of Pittsburgh Medical Center, has shown initial promise in improving the function of a small group of stroke patients.

HNT neurons originate from a rare human cancer characterized by the presence of immature or "progenitor" cells. These rapidly dividing tumor cells have the capacity to differentiate into neurons, each a clone of the original cells.

The cells can be treated with retinoic acid in the laboratory to prompt them into becoming fully committd, non-dividing neurons. Research in both animals and humans has shown that these hNT neurons do not revert to cancer cells.

The USF team studied three groups of rats with severe SCI. One group was administered hNT neurons immediately following injury, another received transplants two weeks after SCI injury, and the third, a control group, received no transplant.

The spinal cord, which runs from the brain to the end of the spine, is like an electrical circuit that sends messages to and from the brain to the rest of the body. If the spinal cord is damaged or severed, however, the electrical activity either stops from the point of injury downward or provides faulty messages.

All seven animals in the delayed transplant group recovered electrical activity in the spinal cord neurons that control muscle movement. Only two of nine animals in the immediate transplant group did. In addition this electrical activity — known as motor evoked potentials or MEPs — measured much stronger in the delayed transplant group than in rats receiving hNT neurons immediately after injury. The untreated SCI rats had no improvement in motor neuron transmission.

The researchers suspect that the better recovery results in the animals with delayed transplants, compared to those transplanted right after injury, may be due to a less hostile immune environment as time passes. Immediately following injury, Dr. Saporta said, inflammatory substances called cytokines recruit immune cells to clear all foreign material away from the area of injury — including, perhaps some of the transplanted hNT neurons.

Pathological examination showed that the transplanted hNT neurons, injected into the spinal cord at the site of injury, maintained the characteristics of neurons. The cells sprouted fibers, or axons, that grew into the undamaged, intact portions of the spinal cord above and below the injured area.

Although two transplanted animals were able to bear weight, none of the rats walked following treatment with the dose of hNT neurons administered in this study.

The transplanted cells appear to fill in the area of damage and re-establish a neural connection, Dr. Saporta said. "This suggests it may be possible to teach the spinal cord, through rehabilitation, how to send out appropriate signals to the muscles so the animal can walk again … That’s the next step."

Layton BioScience Inc. of Atherton, CA, holds the license for hNT neuron transplantation technology and is developing the cells for the treatment of several neurological disorders.

In addition to Dr. Saporta and Dr. Sanberg, other authors of the study were Shahram Makoui, MD; Alison Willing, PhD, and David Cahill, MD, all of the USF Center for Aging and Brain Repair; and Marcel Daadi, PhD; of Layton Bioscience, Inc.

Anne DeLotto Baier | EurekAlert!

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