Neighborly Care Keeps Stem Cells Young
ScienceDaily (Oct. 11, 2007) — A stem cells' immediate neighborhood,
a specialized environment also known as the stem cell niche, provides
crucial support needed for stem cell maintenance. But nothing lasts
forever, found scientists at the Salk Institute for Biological
Studies. During the aging process, the level of support drops off,
diminishing the stem cells' ability to replenish themselves (self-
renew) indefinitely.
The notion that the stem cell microenvironment is aging will
certainly influence how we think about using stem cells in
regenerative medicine," says Leanne Jones, Ph.D., an assistant
professor in the Laboratory of Genetics who led the study. "You can
manipulate stem cells and propagate them in a dish, but many
recipients of stem cell replacement therapies will be older
individuals. If the stem cell niche has aged, it might not be capable
of supporting the transplanted stem cells."
In an article published in the Oct. 11, 2007 issue of Cell Stem Cell,
the researchers show that in older flies a steep decline in the
growth factor unpaired (upd), which is necessary to maintain stem
cells, results in fewer stem cells in the testis of the fruit fly
Drosophila. Identifying the reasons for reduced upd expression could
reveal how aging leads to changes in stem cell behavior, and
counteracting these changes may slow the loss of adult stem cells
during aging.
Adult stem cells serve as a reservoir of cells for repair of damaged
tissue throughout the life of an individual, but the maintenance and
regeneration of tissues, such as skin, liver, blood and muscle,
dramatically decrease with age. "Before we had embarked on our
studies, we knew that tissue regeneration was affected by aging, but
there really wasn't a good system where all the niche components were
known and you could ask, 'so what is changing?' " noted senior
research associate Monica Boyle, Ph.D., who co-authored the study
with Chihunt Wong, a graduate student in the lab.
In the Drosophila testis, however, the whole system has been laid
out, and stem cells can be readily identified -- a major hurdle for
most other types of stem cells. The stem cells sit at the tip of the
testis surrounding a cluster of somatic cells called the apical hub.
As a stem cell divides, one daughter cell, called a gonialblast,
moves out of the niche in an orderly fashion to generate mature sperm
cells. The daughter cell that stays put in the niche retains its stem
cell identity.
In an earlier study, Jones had shown that the hub cells secrete the
self-renewal factor upd, which signals neighboring stem cells to
maintain stem cell fate, making hub cells an essential component of
the stem cell niche. Artificially increasing the levels of
upd,results in tumor-like masses of stem cells.
The current study focused on the influence of aging on the behavior
of stem cells in the male germline. Boyle and Wong started by
comparing the number of stem cells in young (1-2 days old), middle-
aged (30 days old) and old (50 days old) flies. The average fruit fly
lives around 40 days. Over time, stem cell numbers fell from an
average of 8.3 in young flies to 5.1 in old flies, explaining the
observed decrease in spermatogenesis in aged males.
The number of hub cells on the other hand remained unchanged,
prompting the researchers to scrutinize the molecular signals that
govern the behavior of stem cells in fruit flies. When they measured
the levels of upd in the testes of aging males, they found a sharp
decline in the well-known self-renewal factor. In contrast, forced
expression of upd within niche cells delayed the loss of germline
stem cells in older males.
"Taken together, our results suggest that over time the niche is
changing to the point where you start losing self-renewing stem
cells," says Boyle. In fact, "compromised niche function may lead to
the selection of stem cells that no longer depend on self-renewal
factors produced by its environment. Such cells could be the
precursors to cancer stem cells that contribute to tumorigenesis in a
variety of tissues."
"This is really the first description of a molecular factor that's
secreted by the niche and decreases over time," says Wong. "This is
an important step in our understanding of environmental influences on
the aging process of stem cells."
Research Assistant Michael Rocha also contributed the study.
This work was funded by grants from the G. Harold and Leila Mathers
Charitable Foundation, the Ellison Medical Foundation, the American
Federation for Aging Research and the NIH.
The Salk Institute for Biological Studies in La Jolla, California, is
an independent nonprofit organization dedicated to fundamental
discoveries in the life sciences, the improvement of human health and
the training of future generations of researchers. Jonas Salk, M.D.,
whose polio vaccine all but eradicated the crippling disease
poliomyelitis in 1955, opened the Institute in 1965 with a gift of
land from the City of San Diego and the financial support of the
March of Dimes.
Adapted from materials provided by Salk Institute.
http://www.scienced
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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