NINDS Research Offers Hope for Transplantation and Regeneration

For release: Wednesday, November 10, 1993

Age-old dogma held that the central nervous system could not regrow or recover, dampening hopes for recovery from spinal cord injury and other neurological disorders. But recent results from scientists at the National Institute of Neurological Disorders and Stroke (NINDS) offer a glimpse of how basic research promises approaches for restoring and repairing damaged nerves. NINDS scientists will present their findings in three poster sessions at this year's meeting of the Society for Neuroscience, at the Washington D.C. Convention Center, November 7-12.

In one key study, NINDS scientists successfully regenerated myelin along a significant stretch of spinal cord by transplanting special, long-lived glial cells into myelin-deficient rats. Glial cells, found in many forms throughout the nervous system, play an important role in supporting and providing nutrients to the body's nerve cells. Myelin, a fatty substance that coats many of the body's nerves, acts as insulation to speed communication of commands between the brain and body. In multiple sclerosis, which affects about 250,000 Americans, destruction of myelin disrupts control of movement, often causing disability and paralysis.

"We are excited because this is the first demonstration that transplants from this glial cell line can yield remyelination along part of the spinal cord in this animal model," said Monique Dubois-Dalcq, Ph.D., chief of the NINDS Laboratory of Viral and Molecular Pathogenesis. The study,* to be presented by NINDS scientist Ulrike Tontsch, Ph.D., from the same laboratory, was performed in close collaboration with David Archer, Ph.D., and Ian Duncan, Ph.D., at the University of Wisconsin in Madison.

In the study, the special line of rat glial cells were divided through more than 30 life cycles, then cells from the line were transplanted into 12 myelin deficient rats. After 13 days, studies showed that the cells reproduced, changed to oligodendrocytes (myelin-producing cells), churned out patches of myelin, and migrated up to 7 millimeters along the animals' spinal cord. "On a cellular level, that is a lot of division and movement," said Dr. Dubois-Dalcq. "It demonstrates that these cells are surviving and reproducing, as well as making myelin to give fairly extensive repair." Scientists say their findings demonstrate that these cells are a key resource for today's transplantation research and suggest that similar human cell lines, if established, will have potential for future treatment of myelin-damaging disorders.

In another study offering hope for regrowing damaged nerves, a team of NINDS scientists identified several chemicals that help neurons adhere to glass surfaces, enable them to survive on these surfaces, and direct their growth along minute parallel lines. "While what we're doing is very basic, our hope is that these chemicals could eventually be used in combination with special implantable tubes to promote regeneration of motor neurons in people with spinal cord injury," said Dr. Anne Schaffner, of the NINDS Laboratory of Neurophysiology and presenter of the current study.** The study was conducted in collaboration with James J. Hickman, Ph.D., of Science Applications International Corporation in McLean, Virginia.

In their experiments, scientists grew rat fetal tissue taken from the brain and spinal cord on a variety of chemically treated glass surfaces for 2 weeks. Testing 15 different compounds containing amines (organic compounds containing nitrogen), they identified 7 that helped spinal cord neurons to grow, while 5 compounds spurred growth and survival of brain neurons taken from the hippocampus (part of the brain important for memory). And with some one of the chemicals, scientists were able to create simple striped patterns by depositing thin lines of the chemicals on glass surfaces -- a technique that may prove useful in achieving functional recovery from nerve trauma.

"Our research also offers new insights on the physiology of nerve growth. Eventually, we also hope to use these techniques to control the type of nerve growth that is produced," said Dr. Schaffner. "In people with spinal cord injury, scars that form in the remaining tissue block the nerves' axons from regrowing, even though they have the capacity. Using chemicals such as these in future implants may enable scientists to circumvent this problem."

In a third recent finding, NINDS scientists have shown that nude rats are useful for testing the survival of human nerve grafts. These rats will serve as recipients in future experiments that will attempt to cryopreserve (freeze without killing) human nerves for banking and subsequent transplantation. "Our goal is to cryopreserve human nerves for transplantation into patients who have traumatic nerve damage or neurological disease," said Andrew Zalewski, M.D., chief of the Neuronal Regeneration Section in the NINDS Laboratory of Neural Control. "If successful, cryopreservation would enable scientists to establish a bank of nerve tissue from donors for use in transplantation. Using preserved nerves from this bank would allow surgeons to choose the best match between donors and recipients, thus reducing the need for immunosuppressive drugs. In addition, physicians would also have time to expose the recipient to antigens. They could then possibly induce specific immune tolerance to prevent rejection of the foreign nerve graft." Antigens are small molecules found on the surface of cells that trigger rejection when foreign tissues are placed in a recipient.

In the study,*** scientists transplanted pieces of human nerve into nude rats, which lack most immune functions, and checked for evidence of graft survival over periods ranging from 14-82 days. "The human nerve grafts survived in nude rats whereas they were rejected in normal rats," said Nabil Azzam, Ph.D., the NINDS biologist who will present the recent findings. "Furthermore, in nude rats, the rat nerves grew into the foreign grafts, where they were ensheathed and frequently myelinated by cells from the human nerve tissue."

"Our results are a critical step forward in our work toward cryopreservation, because we now have a model that allows us to study the fate of cryopreserved nerves without the expected problem of rejection," Dr. Azzam added. These NINDS scientists have previously demonstrated that they can successfully cryopreserve rat nerves. "Now we are equipped to study the viability of human nerves after cryopreservation," said Dr. Azzam.

"Taken as a whole, this ongoing basic research points toward an exciting future for transplantation and regeneration in the damaged nervous system," said Patricia A. Grady, Ph.D., acting director, NINDS. "This research offers new hope that, one day, physicians will be equipped with treatments to foster recovery in the millions of Americans suffering from disabling damage to the nervous system."

The NINDS, one of the 17 National Institutes of Health in Bethesda, MD, is the nation's leading supporter of research on brain and nervous system disorders, funding a wide array of basic research exploring the potential of transplantation and regeneration for combatting neurological disease.

*Abstract #460.5: "Myelination by Cells from the DG-4 Glial Cell Line Following Transplantation into the Myelin Deficient Rat Spinal Cord." Presenter: Dr. Ulrike Tontsch, NINDS.

**Abstract #535.11: "Several Chemically Defined Surfaces are Conducive to the Adhesion, Survival, and Directed Growth of Embryonic Hippocampal and Spinal Cord Neurons In Vitro." Presenter: Dr. Anne Schaffner, NINDS.

***Abstract 716.3: "Survival of Human Nerve Grafts in Nude Rats." Presenter: Dr. Nabil Azzam, NINDS.

Date Last Modified: Tuesday, March 08, 2005

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