Institute
researchers have discovered a previously unidentified cell in the human brain
that is capable of generating mature brain cells. The discovery could lead
to new therapies for human brain diseases such as multiple sclerosis (MS).
Bruce D. Trapp, PhD, Chair of the Institute's Department of Neurosciences and a leading multiple sclerosis researcher, said beta 4 tubulin cells, or beta T4 cells, are scattered throughout a region of the brain called the subventricular zone. This zone is known to be the major source of stem and other primitive cells in the developing and adult brain.
“Strategies for cell replacement to treat neurodegenerative diseases are very attractive and offer therapeutic possibilities. One example is generating the cells needed to replace the myelin that surrounds, protects and nourishes the neurons in the central nervous system. It's the loss of this myelin that causes lesions in multiple sclerosis brains,” Dr. Trapp said.
Oligodendrocyte progenitor cells (OPCs) generate new oligodendrocytes, which are required to produce myelin. “Unfortunately, OPC growth is limited, so MS lesions often don't remyelinate. Stimulating other types of precursor cells shows great potential in promoting oligodendrocyte production and remyelination in MS patients,” Dr. Trapp said.
Dr. Trapp's research points to beta T4 cells as one of the precursor cells that can generate OPCs.
The presence of beta T4 cells in the subventricular zone peaks during the latter stages of fetal brain development, suggesting the cells' role in generating new glial cells during brain development. The beta T4 cells are also significantly increased in the subventricular zones that border MS lesions in the white matter of brains.
“In our research, we observed that the myelin generated by a relatively small number of transplanted beta T4 cells exceeded that of another known progenitor cell,” Dr. Trapp said. “It remains to be determined if beta T4 cells possess all properties of stem cells. There may be more than one type of stem cell in the brain. The potential of stem cell therapeutics to treat neurodegenerative disease requires additional studies of stem cells in human brains.
“But we propose that beta T4 cells represent a cellular source for the latter stages of myelination and possibly neural repair in the central nervous system” he said. “They could be a promising new direction for cell replacement therapies for multiple sclerosis patients.”
Dr. Trapp's collaborators include Chuanshen Wu, PhD, Ansi Chang, MD, Maria C. Smith, Roy Won, Xinghua Yin, MD, Susan M. Staugaitis, MD, PhD, and Grahame Kidd, PhD, of the Institute's Department of Neurosciences; Dimitri Agamanolis, MD, of the Department of Pathology at Akron Children's Hospital; and Robert H. Miller, PhD, of the Department of Neurosciences at Case Western Reserve University School of Medicine. The findings appeared in the Journal of Neuroscience ( www.jneurosci.org/ June 16, 2009; 29). The research was supported by grants from the National Institutes of Health's National Institute of Neurological Disorders and Stroke and the National Multiple Sclerosis Society.