Abstract
Adult stem cells (ASCs) were long suspected to exist in the endometrium. Indeed, several types of endometrial ASCs were identified in rodents and humans through diverse isolation and characterization techniques. Putative stromal and epithelial stem cell niches were identified in murine models using label-retention techniques. In humans, functional methods (clonogenicity, long-term culture, and multi-lineage differentiation assays) and stem cell markers (CD146, SUSD2/W5C5, LGR5, NTPDase2, SSEA-1, or N-cadherin) facilitated the identification of three main types of endogenous endometrial ASCs: stromal, epithelial progenitor, and endothelial stem cells. Further, exogenous populations of stem cells derived from bone marrow may act as key effectors of the endometrial ASC niche. These findings are promoting the development of stem cell therapies for endometrial pathologies, with an evolution towards paracrine approaches. At the same time, promising therapeutic alternatives based on bioengineering have been proposed.
Highlights
Stem cells are undifferentiated cells capable of simultaneously self-renewing and differentiating into multiple tissue-specific cell types under appropriate stimuli [1,2]
Even though endometrial Adult stem cells (ASCs) have been described in different mammals, such as cows [22], pigs [23], sheep [24], horses [25], and non-human primates [26], in this review we focus on the discovery of stem cells in mice and humans, pointing out how these ASCs were identified and describing the different techniques employed (Figure 1)
Different studies in animal models corroborate this paracrine hypothesis by elucidating low stem cell engraftment when applied to a damaged endometrium [105]
Summary
Stem cells are undifferentiated cells capable of simultaneously self-renewing and differentiating into multiple tissue-specific cell types under appropriate stimuli [1,2]. 8-10 litters during their reproductive life, so active repair and regeneration mechanisms in the endometrial mucosa are critically important [16] This pronounced remodeling ability and the later proliferative changes seen in adult mammals have driven the hypothesis that there is a niche of ASCs in the endometrium that is activated in every cycle [17,18]. Alterations in this endogenous niche could be responsible for endometrial pathology, causing fertility problems [19] Endometrial pathologies such as Asherman syndrome (AS), caused by the presence of intrauterine adhesions [20], or endometrial atrophy (EA), characterized by an atrophic and usually thin endometrium [21], could originate from insufficient production of endogenous cells and/or a non-functional ASC niche. We highlight the value of pre-clinical models of stem cell therapy to treat AS and EA
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