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 between 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," said Alfredo
Quinones-Hinojosa, lead author of the study and an
assistant professor in the
Department of
Neurosurgery at the 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, Quinones said. 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 on 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 gives us a better understanding of
the organization of this SVZ and the cell-to-cell
interaction throughout the SVZ," he said.
The study also revealed that there were displaced
ependymal cells in the SVZ that should not be there. And
although no firm connection has been established between
astrocytes and ependymal cells, Quinones says, the fact
that they are both in this region warrants further study.
"We do not think that ependymal cells are stem cells,"
he said. "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 said.
Quinones says that 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 it was OK and then saved tissue to study it,"
he said.
Quinones says that 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, supported by a grant from the National
Institutes of Health, 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.