WESTPORT, CT (Reuters Health) Jan 03 - Infusing transforming growth factor-alpha (TGF-alpha) into the forebrain of adult rats with brain lesions causes proliferation, migration, and differentiation of neural stem cells. The findings are published in the December 19th issue of the Proceedings of the National Academy of Sciences.
"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," Dr. James Fallon from the University of California, Irvine, said in a university statement. "[Stem cells] 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."
Dr. Fallon and colleagues treated adult rats with 6-hydroxydopamine to destroy dopaminergic neurons in the substantia nigra, then continuously infused TGF-alpha into the forebrain.
TGF-alpha treatment led to a marked increase in the expression of the epidermal growth factor receptor in the subventricular zone, which the authors note is rich in pluripotent stem cells. In addition, the subventricular zone thickened within a week of TGF-alpha infusion, with the ridge of proliferating neuronal and glial progenitors later migrating towards the TGF-alpha infusion site. Soon afterwards, the researchers observed an increase in differentiated neurons in the striatum.
To see if the repopulation of neural cells in the striatum led to functional recovery, they examined rotation behavior in response to apomorphine. Lesioned rats treated with TGF-alpha had a significant 31.5% improvement compared with control animals, they found.
"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," Dr. Fallon said. "We know that there are receptors for TGF-alpha 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."
However, he cautioned that "while a simple administration of TGF-alpha 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 the journal, Dr. Fallon and colleagues note that increased levels of TGF-alpha have been found in some patients with Parkinson's disease, and could represent an endogenous trophic factor in the nervous system. However, they suggest that these levels may be too low to make up for neural loss after injury, and administering TGF-alpha over a threshold value could lead to regeneration and reversal of clinical symptoms.
Proc Natl Acad Sci USA 2000;97:14686-14691.
2000 Reuters Ltd.