Stem Cells May Be Building Blocks of Genitourinary Repairs
September 13, 2007
CLAYTON, Australia, Sept. 13 -- A small number of special cells that
resemble mesenchymal stem cells, bearing the possible application for
major anatomic repairs, have been found in human endometrium,
investigators have found. Action Points
Explain to interested patients that the endometrium, the mucosal
lining of the uterus, appears to contain a small population of stem
cells that could be used in tissue engineering to repair anatomic
defects such as pelvic floor prolapse.
Explain that the studies were performed only in laboratory
experiments, and that therapies based on the discovery, if any may be
a decade or more away.
"The most exciting property of mesenchymal stem cells is their in
vivo differentiation capacity, as they can repair or induce repair of
damaged muscles and ischemic heart muscle, and survive and
differentiate into astrocytes in the brain," they wrote. "Thus,
mesenchymal stem cells have immense therapeutic potential."
The most likely early therapeutic application of the discovery would
involve the use of autologous mesenchymal stem cells for anatomic
repair of conditions such as pelvic floor prolapse, Dr. Gargett
speculated.
"We believe that using a combination of biological scaffold and a
woman's own mesenchymal stem cells might provide a solution that
would ensure a longer lasting firm natural tissue that would be a
superior support for the prolapsed uterus," she said.
Observation of the impressive regenerative properties of endometrium -
- it grows 4 to 7 mm within four to 10 days of every menstrual cycle -
- led Dr. Gargett and Schwab, a Ph.D. candidate working in her lab,
to explore the possibility of isolating mesenchymal stems cells from
the tissue.
But to do so, they first had to figure out how to find them -- no
mean feat, because many of the surface receptors in mesenchymal stem
cells expanded in culture, such as CD29 or CD105, are not unique to
the cells, and can be found as markers on many other cell types, the
authors noted.
"We had previously detected that mesenchymal stem cells were present
in the human endometrium but we were unable to isolate the
mesenchymal stem cells, which was a big drawback in studying their
properties," said Dr. Gargett. "The major finding of this study was
the identification of two markers which enabled the prospective
isolation of mesenchymal stem cell-like cells from human endometrial
tissue."
They focused on two perivascular cell markers in endometrial tissue --
platelet-derived growth factor-receptor b (PDGF-b), which is
expressed that colony-forming endometrial stromal cells, and CD146, a
member of the immunoglobulin superfamily, which is also an
endothelial cell marker.
Using high-speed fluorescence activated cell sorting of endometrial
tissue, they found that only 1.5% of the cells expressed both markers
and were therefore likely candidates for being the elusive
endometrial mesenchymal stem cells.
To determine whether the isolated cells, found in endometrial stroma,
were capable of differentiation into multiple cell types, they tested
them for mesenchymal stem cell-like properties using functional
assays. They found that the sorted cells bearing both receptors had a
greater than 15-fold enrichment of colony-forming endometrial stromal
cells compared with cells that had neither receptor on their
surfaces.
In addition, when colonies of the cells were pooled, expanded in
culture, and exposed to induction factors for osteocytes, adipocytes,
myocytes and chondrocytes, they differentiated into the corresponding
cell types.
In the final step, the investigators attempted to nail down the
location of the cells with immunohistochemistr
samples, and found evidence that they are located perivascularly in
the endometrium.
"The fact that the cells expressing the two markers were located in
the perivascular region strengthens our case that we have isolated
mesenchymal stem cells, because mesenchymal stem cells from bone
marrow and fat are found around blood vessels too," Dr. Gargett
said. "It also gives us clues as to how they might function in
repairing and regenerating new endometrium each month."
Curettage or biopsy is likely to be the most efficient means of
mesenchymal stem cell-collection for use in autologous tissue repair.
Postmenopausal women could be given a short course of hormone
replacement therapy to expand the endometrium prior to harvesting,
Dr. Gargett said.
"We also believe that the identification of the mesenchymal stem
cells in human endometrium gives us the opportunity to investigate
their possible role in the development and pathogenesis of common
gynecological disorders associated with abnormal endometrial growth,
such as endometriosis and adenomyosis,
The authors noted that because their differentiation assays used
pooled clonally derived cells rather than clones expanded from a
single cell, they were not able to determine the true differentiation
potential of a single cell carrying both the CD146 and PDGF-b
receptors. They are not quite ready, therefore, to definitively
declare that the cells they had identified are true mesenchymal stem
cells.
The study was supported by the National Health and Medical Research
Council of Australia. Author conflicts of interest were not
reported.
Additional Stem Cell Research Coverage
Primary source: Human Reproduction
Source reference:
Gargett CE and Schwab KE. "Co-expression of two perivascular cell
markers isolates mesenchymal stem-like cells from human endometrium.
Hum Reprod doi:10.1093/
http://www.medpaget
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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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