15710.3 Identification of EnSCs in Murine Models
The presence of regenerating EnSC populations in murine models was detected
using label-retaining cell (LRC) approach, wherein animals were injected with the
thymidine analogue, bromodeoxyuridine (BrdU), which incorporates into genomic
DNA during the replication phase of mitosis. The tissue of interest was examined
for cells which retain this label after a prolonged chase period. Though there are
evidences supporting the existence of a small population of uterine stem cells in
mouse using the LRC approach, their exact location is unclear [ 7 ]. Chan and Garget
reported that around 3% of epithelial cells and 6% of stromal cells adjacent to the
luminal epithelium at the endometrial myometrial junction are LRCs [ 24 ]. Also,
these epithelial and stromal LRCs differentially express estrogen receptor-1 (Esr1
or ERα) [ 24 ]. Contrary to this report, Cervelló et al. reported that LRCs are present
only in the stromal compartment and not in the epithelial compartment [ 25 ]. Yet
another study reported lack of LRCs in the stromal cell compartment [ 26 ] but iden-
tified epithelial LRCs in the glandular epithelium. The discrepancies in existing data
warrant a detailed study on understanding the source of regenerative endometrium
in murine models.
10.4 Markers Identifying Human EnSCs
Human EnSCs show positivity for expression of bone marrow stem cell markers
like CD9, CD13, CD14, CD29, CD31, CD44, CD73, CD90, CD105, CD117,
CD133, CD146 [ 27 ], but negative for STRO-1, CD31 (endothelial) and CD34 (hae-
matopoietic stem cell and endothelial) markers [ 28 ]. Majority of the studies till date
follow the above panel for characterising the isolated EnSC populations. Separation
and purification of endometrial MSC-like cells (eMSCs) is reported to be efficient
on basis of their co-expression of two perivascular markers, cluster of differentia-
tion 140b (CD140b; platelet-derived growth factor receptor b (PDGFRb]) and
CD146 [ 29 ]. Other markers such as Musashi-1(neural stem cell marker), NAC1
(embryonic stem cell marker [ 30 ], MSI1 and NOTCH1, which maintain stem cells
in an undifferentiated state, are also reported to be expressed by EnSCs [ 1 ]. Tissue
non-specific alkaline phosphatase, leucine rich repeat containing G protein-coupled
receptor-5 (Lgr-5) [ 31 , 32 ] and W5C5 [ 33 ] are yet another set of markers that local-
ize to a perivascular location in human endometrium and may be useful for the
prospective isolation of EnSCs. Nevertheless, current research lacks evidence for a
single specific marker for identifying endometrial stem/progenitor cells that distin-
guish them from their mature progeny. Hence, studies exploring stem cell isolation
from endometrial tissues rely on using a cocktail of markers and functional proper-
ties of stem cells such as clonogenecity, proliferative potential and differentiation
into one or more lineages [ 7 ].
10 Uterine Stem Cells and Their Future Therapeutic Potential in Regenerative Medicine