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[ 43 ]. The hypothesis that stem/progenitor cells contribute to pathogenesis of endo-
metriosis, may account for all existing theories explaining the origin of endometri-
otic implants. The retrograde menstruation theory can be supported by the detection
of stem cells in the basalis layer of the endometrium that are shed through the fal-
lopian tube to establish endometriotic implants. The coelomic metaplasia theory can
be supported by the findings locating stem cells derived from the bone marrow in the
endometrium. Embryonic rest theory can be supported by the presence of stem/
progenitor cells that persist in the remnants of the mullerian system that form endo-
metriotic implants. Bone marrow derived stem/progenitor cells are likely to travel to
distant ectopic sites via the lymphovascular spaces supports the theory of lymphatic
spread.
Recently, we reported several immuno-phenotypic differences between healthy
endometrial (eutopic) and endometriotic (ectopic) MSCs [ 17 ]. The study addressed
differential gene expression for an array of pattern recognition receptors (PRRs) and
pro-inflammatory cytokines along with markers of migration and angiogenesis
among eutopic and ectopic MSCs. Our findings suggest that, though these two cell
types exhibit similar characteristic markers and differntiation potentials, ectopic
MSCs possess an increased level of TLRs, collectins, pro-inflammatory cytokines
and migration and angiogenesis markers. They exhibit a distinct immune-phenotype
compared to eutopic MSCs. This differential immunophenotype plausibly contrib-
ute to the reduced immunosuppressive property of ectopic MSCs and thereby patho-
genesis of endometriosis (Fig. 10.3). However, further in depth molecular studies
are warranted to identify the differentially expressed factors of eutopic and ectopic
MSCs to conclude the exact role of stem cells contributing the pathogenesis of
endometriosis.
10.7 Therapeutic Utility of Uterine Stem Cells
The ease in availability of uterine stem cells marks its potential to be used in regen-
erative medicine and autologous stem cell therapies. A number of studies report the
therapeutic utility of EnSCs in several in vitro and in vivo studies including a few
clinical trials that have opened a new window in the history of regenerative medi-
cine (Tables 10.1 and 10.2).
10.7.1 Eutopic MSCs for Targeted Delivery of Anti-angiogenic
Agents in Endometriosis
Recently, we explored the therapeutic utility of eutopic MSCs for devising a tar-
geted therapy for endometriosis (unpublished data). In the study, we demonstrated
that eutopic MSCs could be genetically manipulated for expressing an anti-
angiogenic factor, soluble FLT-1. Genetically manipulated eutopic MSCs expressed
and secreted sFlt-1, and their therapeutic anti-angiogenic ability was validated in a
K.G. Aghila Rani and T. Madan