15910.5.3 Differentiation
Several studies have reported the potency of EnSCs, right from the endometrium of
the fetus to the postmenopausal period, to differentiate to adipogenic, osteogenic
and chondrocyte lineages, another hallmark feature shown by MSC populations
[ 17 , 39 , 40 ]. These differentiated cells were identified by positive staining with Oil
Red O (for adipogenesis), alizarin red (for osteogenesis), von Kossa (for calcified
extracellular matrix), and Alcian blue (for sulfated proteoglycans) [ 23 ]. The differ-
entiation and proliferation potential of human endometrial cells was attributed to
the modulation of p38 and c-jun pathways [ 41 ].
10.6 EnSCs: Association with Disease Pathogenesis
Several gynaecological conditions are associated with abnormal endometrial prolif-
eration. It is possible that endometrial stem/progenitor cells may play a role in the
pathophysiology of such diseases such as endometriosis, endometrial hyperplasia,
endometrial cancer and adenomyosis [ 2 ]. Alteration in the number, function, regula-
tion and location of EnSCs could possibly be responsible for these endometrial
diseases. Recent studies highlight the possible role of endometrial stem/progenitor
cells in the origin of ectopic endometrial tissue in endometriosis, a major gyneco-
logic concern affecting women in reproductive age [ 9 ]. Leyendecker et al. [ 42 ]
showed that relatively more basalis layer of the endometrium was shed in the men-
strual flow of women with endometriosis compared with that of normal controls.
With the view that the endometrium basalis contains endometrial/stem progenitor
cells and that women with endometriosis have larger volumes of retrograde men-
strual flow, the data by Leyendecker et al. suggested that endometriotic implants
result from the retrograde menstruation of endometrial stem/progenitor cells.
Studies by Kao et al. provided further evidence for the concept that endometrio-
sis is the abnormal growth of endometrial cells sustained by stem cells with high
invasive ability [ 16 ]. Kao et al. identified two different endometrial MSC popula-
tions in women with endometriosis. (1) The eutopic or healthy endometrial MSCs
and (2) the ectopic or endometriotic MSCs [ 16 ]. Although both eutopic and ectopic
MSCs showed similar mesenchymal cell phenotypes, ectopic endometrial MSCs
showed distinctly greater ability of cell migration and invasion and when grown on
scaffold and transplanted in immune-deficient mice, formed many new blood ves-
sels and invaded surrounding tissues than eutopic MSCs.
In another study, Forte et al. reported the expression pattern of a panel of 13 stem-
ness related genes in human endometrial and endometriotic tissues [ 43 ]. The study
concluded that expression of UTF1, TCL1 and ZFP42 showed a trend for higher
frequency of expression in endometriosis than in endometrium, while GDF3 showed
a higher frequency of expression in endometrial samples. The study further sug-
gested a possible role of SALL4-positive cells in the pathogenesis of endometriosis
10 Uterine Stem Cells and Their Future Therapeutic Potential in Regenerative Medicine