Bioengineers have created three-
dimensional brain-like tissue that
functions like and has structural features
similar to tissue in the rat brain and that
can be kept alive in the lab for more than
two months.
As a first demonstration of its potential,
researchers used the brain-like tissue to
study chemical and electrical changes that
occur immediately following traumatic
brain injury and, in a separate experiment,
changes that occur in response to a drug.
The tissue could provide a superior model
for studying normal brain function as well
as injury and disease, and could assist in
the development of new treatments for
brain dysfunction.
The brain-like tissue was developed at the
Tissue Engineering Resource Center at
Tufts University, Boston, which is funded
by the National Institute of Biomedical
Imaging and Bioengineering (NIBIB) to
establish innovative biomaterials and tissue
engineering models. David Kaplan, Ph.D.,
Stern Family Professor of Engineering at
Tufts University is director of the center
and led the research efforts to develop
the tissue.
Currently, scientists grow neurons in petri
dishes to study their behavior in a
controllable environment. Yet neurons
grown in two dimensions are unable to
replicate the complex structural
organization of brain tissue, which consists
of segregated regions of grey and white
matter. In the brain, grey matter is
comprised primarily of neuron cell bodies,
while white matter is made up of bundles
of axons, which are the projections
neurons send out to connect with one
another. Because brain injuries and
diseases often affect these areas
differently, models are needed that
exhibit grey and white matter
compartmentalization.
Recently, tissue engineers have attempted
to grow neurons in 3D gel environments,
where they can freely establish
connections in all directions. Yet these
gel-based tissue models don’t live long
and fail to yield robust, tissue-level
function. This is because the extracellular
environment is a complex matrix in which
local signals establish different
neighborhoods that encourage distinct cell
growth and/or development and function.
Simply providing the space for neurons to
grow in three dimensions is not sufficient.
Now, in the Aug. 11th early online edition
of the journal Proceedings of the National
Academy of Sciences, a group of
bioengineers report that they have
successfully created functional 3D brain-
like tissue that exhibits grey-white
matter compartmentalization and can
survive in the lab for more than two
months.
“This work is an exceptional feat,” said
Rosemarie Hunziker, Ph.D., program
director of Tissue Engineering at NIBIB.
“It combines a deep understand of brain
physiology with a large and growing suite
of bioengineering tools to create an
environment that is both necessary and
sufficient to mimic brain function.”
The key to generating the brain-like
tissue was the creation of a novel
composite structure that consisted of two
biomaterials with different physical
properties: a spongy scaffold made out of
silk protein and a softer, collagen-based
gel. The scaffold served as a structure
onto which neurons could anchor
themselves, and the gel encouraged axons
to grow through it.
To achieve grey-white matter
compartmentalization, the researchers cut
the spongy scaffold into a donut shape
and populated it with rat neurons. They
then filled the middle of the donut with
the collagen-based gel, which subsequently
permeated the scaffold. In just a few
days, the neurons formed functional
networks around the pores of the
scaffold, and sent longer axon projections
through the center gel to connect with
neurons on the opposite side of the donut.
The result was a distinct white matter
region (containing mostly cellular
projections, the axons) formed in the
center of the donut that was separate
from the surrounding grey matter (where
the cell bodies were concentrated).
Over a period of several weeks, the
researchers conducted experiments to
determine the health and function of the
neurons growing in their 3D brain-like
tissue and to compare them with neurons
grown in a collagen gel-only environment
or in a 2D dish.
The researchers found that the neurons in
the 3D brain-like tissues had higher
expression of genes involved in neuron
growth and function. In addition, the
neurons grown in the 3D brain-like tissue
maintained stable metabolic activity for
up to five weeks, while the health of
neurons grown in the gel-only environment
began to deteriorate within 24 hours. In
regard to function, neurons in the 3D
brain-like tissue exhibited electrical
activity and responsiveness that mimic
signals seen in the intact brain, including
a typical electrophysiological response
pattern to a neurotoxin.
Because the 3D brain-like tissue displays
physical properties similar to rodent brain
tissue, the researchers sought to
determine whether they could use it to
study traumatic brain injury. To simulate a
traumatic brain injury, a weight was
dropped onto the brain-like tissue from
varying heights. The researchers then
recorded changes in the neurons’
electrical and chemical activity, which
proved similar to what is ordinarily
observed in animal studies of traumatic
brain injury.
Kaplan says the ability to study traumatic
injury in a tissue model offers advantages
over animal studies, in which
measurements are delayed while the brain
is being dissected and prepared for
experiments.
“With the system we have, you can
essentially track the tissue response to
traumatic brain injury in real time,” said
Kaplan. “Most importantly, you can also
start to track repair and what happens
over longer periods of time.”
Kaplan emphasized the importance of the
brain-like tissue’s longevity for studying
other brain disorders. “The fact that we
can maintain this tissue for months in the
lab means we can start to look at
neurological diseases in ways that you
can’t otherwise because you need long
timeframes to study some of the key
brain diseases,” he said.
Hunziker added, “Good models enable solid
hypotheses that can be thoroughly tested.
The hope is that use of this model could
lead to an acceleration of therapies for
brain dysfunction as well as offer a
better way to study normal brain
physiology.”
Kaplan and his team are looking into how
they can make their tissue model more
brain-like. In this recent report, the
researchers demonstrated that they can
modify their donut scaffold so that it
consists of six concentric rings, each able
to be populated with different types of
neurons. Such an arrangement would mimic
the six layers of the human brain cortex,
in which different types of neurons exist.
As part of the funding agreement for the
Tissue Engineering Resource Center,
NIBIB requires that new technologies
generated at the center be shared with
the greater biomedical research
community.
“We look forward to building collaborations
with other labs that want to build on this
tissue model,” said Kaplan.
Source:
http://www.sciencedaily.com/releases/2014/08/140811151119.htm

Ok

If this thread doesn't make front page.,. I weep for nairaland