A study led by a Johns Hopkins neurosurgeon has provided the first comprehensive map of a part of the adult human brain containing astrocytes, cells known to produce growth factors critical to the regeneration of damaged neural tissue and that potentially serve as brain stem cells. The mapping study -- using special microscopes and chemical analysis of 42 samples of brain tissue taken at autopsy from seven people, and 43 samples of tissue removed with permission from living patients as part of unrelated neurosurgical procedures -- also revealed evidence of the move of cells lining the ventricles, or ependymal cells, to the same area of the brain, a discovery expected to provide further insight into the critical relationship among ependymal cell, astrocytes and potential brain stem cells.
"Although we have not confirmed the existence of human brain stem cells in vivo or their ability to migrate to parts of the brain that need repair, what we have learned from this complete map of the lateral wall of the subventricle zone or SVZ, including the unexpected existence of ependymal cells there, suggests that additional research is warranted," says Alfredo Quinones-Hinojosa, M.D., lead author of the study and an assistant professor in the Department of Neurosurgery at the Johns Hopkins University School of Medicine. "If there is stem-cell-like activity in the SVZ, this discovery could help pave the way for a number of therapeutic treatments for treating brain cancer, neurodegenerative diseases and brain damage."
The subventricle zone refers to tissue and cells that lie next to the ventricles or tubes located in the center of the brain that act as conduits for the cerebral spinal fluid that bathes the entire brain. The ependymal layer is a layer of cells that make up the outer wall of these tubes. Behind that layer lies the SVZ.
Previous studies have shown that astrocytes located in rodent SVZs travel to the olfactory bulb, where they develop into new brain cells, according to Quinones. However, the human SVZ is structured differently. And even though astrocytes have been identified in the adult human SVZ, there is no evidence that they migrate to other parts of adult brains and behave like brain stem cells.
Because the potential existence of human brain stem cells could have an enormous impact in understanding and subsequently developing treatments for brain diseases and injury, Quinones says his team set out to learn more about how new cells are formed in this critical area in the adult human brain.
"To date, only a small portion of this region has been mapped. This new study give us a better understanding of the organization of this SVZ and the cell-to-cell interaction throughout the SVZ," says Quinones.
The study also revealed that there were displaced ependymal cells in the SVZ that should not be there, according to Quinones. And although no firm connection has been established between astrocytes and ependymal cells, the fact that they are both in this region warrants further study.
"We do not think that ependymal cells are stem cells," he says." However, they might mutate and become cancerous. They might be communicating or relating to astrocytes. At this point, we are only scratching the surface. But if we can achieve a better understanding of why these cells are there and how they function and/or migrate, this could help us treat brain tumors such as ependynomas or even gliomas as well as help us treat neurodegenerative diseases and brain trauma," he says.
Quinones says an important aspect of this study is the use of tissue removed during therapeutic surgery that would have otherwise been discarded.
"We used the operating room as an extension of the laboratory. Instead of throwing tissue away, we asked patients if is was Ok and then saved tissue to study it," he says.
Quinones says the next step is to better understand the various roles of astrocytes in the adult human brain and patterns of potential migration of these cells.
The study was conducted while Quinones was at the University of California at San Francisco and included researchers from the Department of Cellular Biology at the University of Valencia in Spain.
This study was supported by a grant from the National Institutes of Health.
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