Neural stem cells, Redefining Therapy
March 10, 2009 | Tuesday | News
Neural
stem cells, Redefining Therapy
Neurodegenerative
disorders might get a permanent cure with the help of rapid progress in
the neuron replacement therapy.
In the early 1990s, researchers revealed that the embryonic nerve cells
injected into brain can migrate throughout the organ, grow into healthy
replacement cells, and help to reverse brain damage thus leading to
treatments for multiple sclerosis and other devastating diseases of the
central nervous system. In the embryo, brain cells are thought to
develop from unspecialized cells called neural stem cells(NSC).
Considering NSCs ability to differentiate into a wide range of cell
types, researchers are trying to use them to replace brain cells that
are damaged by injury or disease.
Research and development
Researchers from the Harvard Stem Cell Institute(HSCI) and Columbia
University took the development further by demonstrating that the
pluripotent stem cells derived from a patient with amyotrophic lateral
sclerosis(ALS) can be differentiated into motor neurons, the brain
cells that are destroyed by ALS, the fatal neurodegenerative disease,
also known as Lou Gehrig’s disease. The researchers believe
that if they can figure out how a person’s motor neurons die,
they can able to figure out the ways to save that person. Scientists
believe that stem cells are the valuable tools to understand the
disease process and create mini-representations of disease or assays
for the purpose of drug screening. This could further help to examine
cellular and molecular defects in motor neurons and glial cells derived
from patients with ALS.
Neural cells derived from human embryonic stem cells are found to
repair stroke-related damage in the brains of rats and led to
improvement in their physical abilities after a stroke. The research
team led by Gary Steinberg hints that the study is small and more work
is needed to determine whether a similar approach would work in humans,
the study also shows the potential of stem cell therapies in treating
strokes.
Human embryonic stem cells possess the ability to transform into any
cell type in the body. Pushing embryonic stem cells to form neural stem
cells and eliminating its possibility to form tumors when
transplanted remain as the main hurdles. Embryonic stem cells are still
immature and retain the ability to renew themselves and produce all
tissue types, they tend to grow uncontrollably to become
tumors consisting of a mass of different cells. Researchers overcame
this hurdle by growing the embryonic stem cells in a combination of
growth hormones that nudged the cells to mature into stable neural stem
cells. After six months in a lab dish, those neural stem cells
continued to form only the three families of neural cells, neurons,
astrocytes and oligodendrocytes.
After ensuring the safety of neural cells, Daadi and co-author
Anne-Lise Maag, a former research assistant, transplanted those cells
into the brains of 10 rats with an induced form of stroke. At the end
of two months, the cells had migrated to the damaged brain region and
incorporated into the surrounding tissue. None of those transplanted
cells formed tumors. Once in place, the transplanted cells helped to
repair damage from the induced stroke. The researchers mimicked a
stroke in a region of the brain that left one forelimb weak, this model
parallels the kind of difficulties people experience after a stroke.
Test conducted at fourth and eighth weeks after the stem cell
transplants showed that the animals were able to use their forelimbs
more effectively than rats with similarly damaged brain regions that
had not received the transplants. Before testing this neural cells in
humans, researchers are trying to ensure the effectiveness of this
approach in animal stroke models.
Future
The past few years have seen major development in the field of NSC
research with more emphasis towards its application in cell replacement
therapy for neurological disorders. However, the clinical application
of NSCs will remain largely unfeasible until a comprehensive
understanding of the cellular and molecular mechanisms of NSC fate
specification is achieved. This understanding will increase the
possibility to exploit the potential of stem cells in order to
manufacture transplantable NSCs that can able to provide a safe and
effective therapy for previously untreatable neurological disorders.
Since the pathology of each of these disorders is determined by the
loss or damage of a specific neural cell population, it is necessary to
generate a range of NSCs that can replace specific neurons or glia
rather than generating a generic NSC population.
In the future, scientists may be able to implant the stem cells
directly into patient’s brains to improve mental illness.
Contrary to past dogma, scientists have discovered that the brain is
continually creating new neurons (neurogenesis) in the hippocampus, an
area of the brain critical for long term memory. Depression has been
associated with reduced neurogenesis in the hippocampus and
antidepressant drugs have the ability to increase neurogenesis. Using
the new deep transcranial magnetic stimulation (TMS) may allow
researchers to selectively target the hippocampus with electrical
stimulation so as to increase the brain’s natural mechanism
of generating new neurons. With a more sophisticated understanding of
the brain, scientists may be able to achieve neurogenesis in brain
areas not normally associated with new neuron growth.
Researchers have already devised techniques to guide the position of
neurons in the brain. They have incorporated iron particles into single
neurons created from stem cells. Using targeted magnetic pulses to
precisely position these newly created neurons in specific brain areas
to improve several conditions. So science will most likely progress to
a better and more controlled creation of new neurons and the precise
placement of those neurons into the requisite brain areas. For extreme
life extension, replacing aging neurons may be necessary from time to
time. In the future, we may be able to use these techniques to
periodically replace dying neurons with new ones. Intelligence
enhancement is another area that stem cells may have some value in the
future. Scientists may be able to increase the amount of neurons in an
individual’s brain in areas that are associated with certain
performance tasks, such as memory, general intelligence and attention.
Overall, we can expect exciting developments in neuron replacement
therapy that could improve many currently devastating health conditions
and potentially enhance normal people’s functioning as well.
Shalini Gupta