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10.2 Origin of Endometrial Stem Cells (EnSCs)
Human endometrium is a dynamic organ, originated from the Mullerian ducts dur-
ing embryonic life while the myometrium with a non-Müllerian origin, is developed
during fetal life [ 4 ]. The endometrium is structurally and functionally divided into
two major compartments: [ 5 ] the functionalis, transient layer containing glands
extending from the surface epithelium and supportive stroma, and [ 6 ] the basalis,
comprising the basal region of the glands, stroma, supporting vasculature, and lym-
phoid aggregates. Endometrium undergoes rapid cycles of regeneration that includes
cellular proliferation, differentiation, and shedding of the functionalis layer during
each round of menstrual cycle [ 7 ]. Although the underlying mechanisms are poorly
understood, this cyclic renewal is likely to be contributed by a residing uterine stem
cell population [ 8 , 9 ]. It is believed that the stem cells residing in the basal endome-
trial layer [ 1 ] migrate to the functional layer and actively participate in the regenera-
tion and remodelling of the endometrium (Fig. 10.1).
Though there are evidences for the presence of regenerating endometrial stem
cell populations, their exact origin remains poorly understood [ 7 ]. The origin of
endometrial stem cells is attributed to a number of possibilities such as [ 5 ] they are
the fetal epithelial and mesenchymal stem cells (MSCs) which remain in the adult
endometrium and continues to replicate in adulthood [ 6 ], the circulating bone mar-
row stem cells that seeds the endometrium either periodically or in response to
injury, or [ 10 ] a combination of both [ 2 , 9 , 11 , 12 ]. Several research groups have
attempted at harvesting these regenerating, clonogenic stem cell populations from
endometrial tissues.
EnSCs can be distinctly classified as epithelial progenitor cells, MSCs, endothe-
lial progenitor cells and endometrial side population cells [ 1 ].
10.2.1 Epithelial Progenitor Cells
Epithelial progenitor cells reside in the basalis layer of the endometrium and are not
shed during the menstrual cycle [ 13 ]. Menstrual blood contains only stromal cell
types and lacks epithelial cells [ 13 ]. The findings corroborate with earlier reports
that clonogenic cells are present both in the active and inactive endometrium, as
inactive endometrium is predominantly basalis and lacks functionalis layer [ 14 ].
10.2.2 Mesenchymal Stem Cells
The presence of clonogenic MSC populations has been detected in the endometrium
of peri-menopausal women, post-menopausal women, and women on oral contra-
ceptives [ 14 ]. Techniques involved in isolation of MSCs from endometrial biopsy
K.G. Aghila Rani and T. Madan