The hippocampus is located in the medial temporal lobe of the brain. In this lateral view of the human brain, the frontal lobe is at left, the occipital lobe at right, and the temporal and parietal lobes have largely been removed to reveal the hippocampus underneath.
Hippocampus (lowest pink bulb) as part of the limbic system
Today I'll point out progress towards an as yet
unrealized category of stem cell treatments involving
the wholesale replacement of entire stem cell populations
and their niches,
to remove age-related damage and sustain tissue maintenance for the long term.
This will become an essential component for any future rejuvenation toolkit.
From a stem cell perspective, rejuvenation has two components: firstly revert
the root causes of signaling changes in blood and tissues that result in stem cell
populations becoming less active; secondly, replace the stem cells
themselves, scores of different types in different locations, to clear out
damaged cells. The root cause of signaling changes in old individuals is,
collectively, all of the forms of
damage listed in the SENS proposals for rejuvenation treatments
- a lot of work is yet to be accomplished there to reach even the initial goals
of prototype treatments across the board. Nonetheless, it is still the case
that replacement of aged stem cell populations with undamaged, pristine stem
cells created from the patient's own cells is an important target for future
development in the stem cell field.
Most stem cell therapies in use today are actually far
removed from this goal: the transplanted cells do not live long, and do not
integrate with recipient tissues. They achieve beneficial effects through a
temporary alteration of the signaling environment that spurs regeneration and
reduces inflammation. In effect the transplant temporarily overrules the
evolved reaction to being aged and damaged and puts sleeping cells back to work
- but without fixing that low level damage. So there can be some degree of
rebuilding of worn tissues and organs, but the causes of aging are still
present and continue to cause harm: cross-links, mitochondrial
mutations, and so forth.
There are exceptions to the outcome of benefits
through signaling mechanisms, however, and these exceptions include types of
therapy in which cells are transplanted into the brain. Some of the earliest
stem cell transplants trialed in humans aimed to treat Parkinson's
disease, for example, and at least some of the transplanted cells
survived and integrated into the brains of patients for the long term. This is
still a considerable distance removed from a controlled repopulation of stem
cell niches in all of the right places and with cells that will pick up tissue
maintenance activities in exactly the right ways, but it is a step in the right
direction. In the research materials linked below, scientists report on further
progress along these lines, and that they were able to create new stem cell
niches in brain tissue seems like an important advance:
Quote:
Although brains - even adult brains - are far more
malleable than we used to think, they are eventually subject to age-related
illnesses, like dementia, and loss of cognitive function. Someday, though, we
may actually be able to replace brain cells and restore memory. Recent work
hints at this possibility with a new technique of preparing donor neural
stem cells and grafting them into an aged brain. The team took
neural stem cells and implanted them into the hippocampus -
which plays an important role in making new memories and connecting them to
emotion - of an animal model, essentially enabling them to
regenerate tissue.
"We're very excited to see that the aged
hippocampus can accept grafted neural stem cells as superbly as the young
hippocampus does and this has implications for treating age-related neurodegenerative
disorders. It's interesting that even neural stem
cell nichescan be formed in the aged hippocampus." The team
found that the neural stem cells engrafted well onto the hippocampus in the
young animal models (which was expected) as well as the older ones that would
be, in human terms, about 70 years old. Not only did these implanted cells
survive, they divided several times to make new cells. "They had at least
three divisions after transplantation. So the total yield of graft-derived neurons and glia (a
type of brain cell that supports neurons) were much higher than the number of
implanted cells, and we found that in both the young and aged hippocampus,
without much difference between the two. What was really exciting is that in
both old and young brains, a small percentage of the grafted cells retained
their 'stemness' feature and continuously produced new neurons."
This is called creating a new 'niche' of neural stem
cells, and these niches seemed to be functioning well. "They are still
producing new neurons at least three months after implantation, and these
neurons are capable of migrating to different parts of the brain. Next, we want
to test what impact, if any, the implanted cells have on behavior and determine
if implanting neural stem cells can actually reverse age-related learning and
memory deficits. That's an area that we'd like to study in the future."
Quote:
As clinical application of neural stem cell (NSC)
grafting into the brain would also encompass aged people, critical evaluation
of engraftment of NSC graft-derived cells in the aged hippocampus has
significance. We examined the engraftment and differentiationof alkaline phosphatase-positive NSCs expanded
from the postnatal subventricular zone (SVZ), 3 months after
grafting into the intact young or aged rat hippocampus. Graft-derived cells
engrafted robustly into both young and aged hippocampi. Although most
graft-derived cells pervasively migrated into different hippocampal layers, the
graft cores endured and contained graft-derived neurons.
The results demonstrate that advanced age of the host
at the time of grafting has no major adverse effects on engraftment, migration,
and differentiation of grafted subventricular zone-neural stem cells (SVZ-NSCs)
in the intact hippocampus, as both young and aged hippocampi promoted excellent
engraftment, migration, and differentiation of SVZ-NSC graft-derived cells in
the present study. Furthermore, SVZ-NSC grafts showed ability for
establishing neurogenic niches in non-neurogenic
regions, generating new neurons for extended periods after grafting. This
phenomenon will be beneficial if these niches can continuously generate new
neurons and glia in the grafted hippocampus, as newly generated neurons and
glia are expected to improve, not only the microenvironment, but also the plasticity and function of the aged
hippocampus. Overall, these results have significance because the potential
application of NSC grafting for treatment of neurodegenerative disorders at
early stages of disease progression and age-related impairments would mostly involve
aged persons as recipients.
https://www.fightaging.org/archives/2016/06/replacing-neural-stem-cells-in-the-aging-hippocampus/
No comments:
Post a Comment