Stem Cells Stimulated By Natural Growth Factor Reverse Damage, Restore Some Function In Adult Brain

The study, conducted in rats, is the first to show that adult brain stem cells can develop into nerve cells in living adult animals, leading to the replacement of damaged brain tissue. If the results can be replicated in humans, they may eventually result in a wide range of new and natural stem-cell based treatments for stroke, nervous system and spinal cord injury and diseases like Parkinson's and Alzheimer's that are marked by degeneration of nerve cells. The study appears in the Dec. 19, 2000, issue of the Proceedings of the National Academy of Sciences.

James Fallon, professor of anatomy and neurobiology--along with his colleagues at UCI and researchers at Stem Cell Pharmaceuticals--found that injecting a human protein called transforming growth factor-alpha (TGF-a) into damaged areas of the brain stimulated stem cells to multiply, migrate and differentiate into a massive number of normal, fully developed nerves. These cells were then able to repair damage and restore the rats' movement ability. Injections of TGF-a into normal rat brain tissue did not stimulate repair; nor does brain damage alone lead to the development of new cells.

"This study is the first to show that stem cells can be induced naturally in large enough numbers and drawn to specific sites of damage, restoring function and replacing damaged cells in the brain," said Fallon. "The stem cells are already in the brain and other organs in small numbers. They can be stimulated in the brain to develop by a growth factor without the need for transplanting stem cells, embryonic tissue or altered cells from outside; instead, we've just stimulated cells that are already there."

Fallon's team includes researchers at Stem Cell Pharmaceuticals Inc., a Seattle-based firm. Fallon serves on the board of scientific advisors for Stem Cell, which provided research support and supplies of TGF-a for the most recent experiments in the study. In addition, Stem Cell has a technology transfer license with UCI to explore the roles of this and other growth factors and nerve-cell receptors in restoring function in neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's, as well as damage caused by stroke and spinal cord injury. Stem Cell Pharmaceuticals and Fallon currently are conducting more experiments in animals to measure the effectiveness of TGF-a (also called GFA-50). These experiments will support the initiation of clinical trials in humans.

The researchers found that when they injected TGF-a into the forebrains of rats, only those with damaged tissue showed signs of significant cell division, cell migration toward depleted and damaged areas, and specialization of cells into new cells in the brain. The new cells appeared to be drawn into damaged areas, replacing destroyed cells.

Scientists think that the process of stem-cell stimulation may occur naturally to replace damaged brain tissue. But when a large brain injury, stroke or degenerative disease like Alzheimer's strikes, the brain's natural repair mechanism may not be able to keep up with so much damage. Adding more natural growth factors like TGF-a to damaged areas may provide the necessary boost.

Stem cells exist in relatively large numbers in embryos but decrease dramatically just before birth and are rare in the adult brain. During development, stem cells divide, migrate to specific parts of the body and develop into all specialized cells of the body, such as the brain, liver, hair and skin. All fully functioning cells ultimately arise from stem cells, which researchers recently have been studying in order to harness the cells' ability to develop into any of a large number of cells. Until this finding, researchers had been unsuccessful at large-scale stimulation of brain stem cells in adults, focusing instead on transplanting cells from other adult and embryonic tissues.

"This finding shows that it is possible to stimulate and control the growth, movement and development of large numbers of stem cells to repair brain injury," Fallon said. "We know that there are receptors for TGF-a in nervous system stem cells. When damaged, enough growth factor can stimulate these cells to reproduce and draw them to damaged areas, resulting in new nerve tissue. While a simple administration of TGF-a worked significantly with rats, we still need to find out if other interacting factors like injury signals in the nervous system regulate the growth of stem cells and can be used to help restore function."

In addition to Stem Cell Pharmaceuticals, Inc., the research was supported by the American Parkinson's Disease Foundation, the American Foundation for Aging Research and UC Irvine's College of Medicine Research Associates.