Scientists discover how to isolate stem cells in womb tissue
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Embargoed: 00.01 hrs London time (BST), Thursday 13 September 2007
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Scientists in Australia have found a way of identifying probable stem
cells in the lining of women's wombs. The finding opens up the
possibility of using the stem cells for tissue engineering
applications such as building up natural tissue to repair prolapsed
pelvic floors. Pelvic floor prolapse is a common condition, affecting
over 50% of women after childbirth; around one in ten women have
surgery and a third of these women require repeated operations to
correct the problem.
In research published online today (Thursday 13 September) in the
journal Human Reproduction [1], Dr Caroline Gargett describes how she
and her PhD student, Ms Kjiana Schwab, identified two markers, CD146
and PDGF-Rß, which they were able to use to isolate mesenchymal stem-
like cells (MSC) from endometrial tissue using a high speed cell
sorting machine (fluorescence activated cell sorting – FACS). Only
1.5% of the endometrial cells sorted in this way expressed both
markers and, therefore could be MSC.
They then investigated the properties of the MSC to discover whether
they really were stem cells, capable of differentiating into a
variety of different cell types. They found the cells were able to
produce clones to form colonies of new cells at a rate that was 15
times greater than produced by the other endometrial cells.
Furthermore, the MSC were able to differentiate into fat, bone,
cartilage and smooth muscle cells in the culture dish. The MSC also
appeared to be located around blood vessels in the endometrium
(perivascular region).
Dr Gargett, a senior scientist at the Centre for Women's Health
Research, Monash Institute of Medical Research, Monash University,
Victoria, Australia, explained: "Colony-forming ability is a property
of adult stem cells, as is the ability to differentiate into
different cell types. 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. It also gives us clues as to how they might function in
repairing and regenerating new endometrium each month."
This is the first time that researchers have been able to use markers
to isolate MSC from the endometrium and also the first study to show
that the properties of these cells mean they are highly likely to be
stem cells.
Dr Gargett said: "We had previously detected that MSC were present in
the human endometrium but we were unable to isolate the MSC, which
was a big drawback in studying their properties. The major finding of
this study was the identification of two markers which enabled the
prospective isolation of MSC-like cells from human endometrial
tissue. This allows us to characterise endometrial MSC so we can
understand their molecular and cellular properties better, compare
them to MSC from other sources, such as bone marrow and fat, use them
for tissue engineering applications, such as making constructs with
biological scaffolds for pelvic floor prolapse surgery, and find
where they are located in endometrium (i.e. around blood vessels);
this gives us a clue as to how they might function in growing new
endometrium each menstrual cycle and how they may have a role in
gynaecological diseases such as endometriosis.
The human endometrium is the only adult tissue that contains a
substantial amount of the connective tissue framework (called stroma)
that regularly regenerates under normal conditions when a woman
menstruates. Because of its regenerative properties, Dr Gargett
believed that it might contain MSC that were responsible for the
monthly regeneration of the stroma and related blood vessels, and
which could be an easily available source of MSC for stem cell
therapy. However, until she identified CD146 and PDGF-Rß as MSC
markers, there were no known markers and therefore no way of
isolating the endometrial MSC.
Her research, using tissue obtained from women aged between 31-49 who
were having hysterectomies, indicates that the MSC are probably
located mainly in the basalis layer of the endometrium, which is the
layer that is not shed during a woman's period. "We think that is
where the MSC should be if they are responsible for producing the
functionalis layer, which grows each month," said Dr Gargett.
This means that, although it might be possible to collect MSC from
menstrual blood, the most likely method of collection would be
curettage or biopsy. "This would not be any more invasive than
collecting MSC from bone marrow or surgical removal (biopsy) of fat
tissue," said Dr Gargett. "MSC could also be collected from
postmenopausal women, whose endometrium is very thin. If these women
are given oestrogen replacement therapy for a very short time (a week
or two) their endometrium will grow to the thickness of a
reproductive age woman and the MSC could be collected without harm to
the woman."
Dr Gargett believes that initial applications for endometrial MSC
would be to use them on the women that they had been retrieved from
(rather than on other people) for gynaecological purposes such as
pelvic floor prolapse. "Pelvic floor prolapse is a common problem
that significantly impacts the lives of many women and they find it
embarrassing to talk about – it is a hidden disorder in need of an
innovative therapy," she explained.
"Clinicians have been using a synthetic mesh as a reinforcement
material to try and reduce the high rate of recurrence of this
condition. While these meshes are often successful, a significant
number of complications arise due to erosion or rejection of the
foreign material. Increasingly clinicians have been trying biological
scaffold material, but this often fails as it lacks cells and the
body breaks it down faster than the body's cells can infiltrate and
strengthen the material. We believe that using a combination of
biological scaffold and a woman's own MSC might provide a solution
that would ensure a longer lasting firm natural tissue that would be
a superior support for the prolapsed uterus.
"We also believe that the identification of the MSC in human
endometrium gives us the opportunity to investigate their possible
role in the development and pathogenesis of common gynaecological
disorders associated with abnormal endometrial growth, such as
endometriosis and adenomyosis.
However, it will probably be at least ten years before applications
from Dr Gargett's findings will be used in the clinic. The next
stages of the research include refining the technique by looking for
further markers and possibly a single marker that could do the same
job as two, and testing the possible tissue-engineering applications
in animal models before they are used in humans.
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[1] Co-expression of two perivascular cell markers isolates
mesenchymal stem-like cells from human endometrium. Human
Reproduction. doi:10.1093/
[2] A form of endometriosis characterised by the invasive, usually
benign, growth of tissue into smooth muscle layer of the uterus.
Notes:
A PDF of the research paper is available immediately from Emma Mason
or from 10am on Tuesday 11 September at:
http://www.oxfordjo
Human Reproduction is a monthly journal of the European Society of
Human Reproduction and Embryology (ESHRE). ESHRE's website is:
http://www.eshre.
Please acknowledge Human Reproduction as a source
Abstracts of other papers in ESHRE's three journals: Human
Reproduction, Molecular Human Reproduction & Human Reproduction
Update can be accessed post embargo from
http://www.oxfordjo
Papers available on request from Emma Mason.
Contact (media enquiries only):
Emma Mason
Tel: +44 (0)1376 563090 Mobile: +44 (0)7711 296 986
Email: wordmason@mac.
http://www.eshre.
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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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