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Stem cells (SCs) play an important role in autologous and even allogenic applications. Menstrual blood discharge has been identified as a valuable source of SCs which are referred to as menstrual blood-derived stem cells (MenSCs). Compared to SCs from bone marrow and adipose tissues, MenSCs come from body discharge and obtaining them is non-invasive to the body, they are easy to collect, and there are no ethical concerns. There is, hence, a growing interest in the functions of MenSCs and their potential applications in regenerative medicine. This review presents recent progress in research into MenSCs and their potential application.

Clinical indications of using MenSCs for various regenerative medicine applications are emphasized, and future research is recommended to accelerate clinical applications of MenSCs. The endometrium undergoes more than 400 cycles of regeneration, differentiation, and shedding over the whole reproductive period of a woman. Human endometrial stem cells play an important role in this cyclic regeneration and repair. Endometrial stem cells (EndoSCs), including epithelial, stromal, and endothelial cells, may contribute to the periodic endometrial regeneration [ ], mainly reside in the perivascular region of both the basalis and functionalis of the endometrium [ ].

When exfoliated in the menstrual blood, these EndoSCs are hence referred to as the menstrual blood-derived stem cells (MenSCs) [ ]. The advantages of MenSCs include non-invasiveness of extraction, high proliferation ability, and short doubling time, and maintenance of chromosome karyotyping after up to 68 generations, which qualifies MenSCs as an ideal source of regenerative cells desperately needed for transplantation, neurological disorders, and cancer therapy, etc.

The endometrium, which consists of luminal epithelium, glandular epithelium, and an extensively vascularized stroma, structurally and functionally falls into two compartments, viz, functionalis and basalis [ ]. Endometrial glands are lined with pseudo-stratified columnar epithelium extending from the luminal epithelium to the endometrial/myometrial junction. The functionalis consists of the upper two thirds of the glands surrounded by loose vascularized stroma. Being a germinal supplier for new functionalis replacement in each cycle, the basalis is composed of the lower one thirds of glands, stroma, and large vessels [ ]. Gargett et al. Considered that human endometrial stem cells include epithelial progenitor cells, endometrial mesenchymal stem cells (eMSCs), and endothelial progenitor cells [ ], while Evans et al. Characterized endometrium-specific stem cells into epithelial progenitor cells, side population (SP) cells, and eMSCs [ ].

Vray crack for revit. Endometrial epithelial progenitor cells Within the first 48 h of menses, with stumps of the gland remaining in the basalis, a rapid repair and re-epithelization of the endometrium lining occurs to cover the exposed basal surface. Epithelial progenitor cell populations locate within the residual glands of the basalis [ ]. Evidence was provided by the presence of colony-forming units (CFUs) in suspension cells from hysterectomy specimens [ ]. These large single cell-derived epithelial CFUs have high proliferative potential and can differentiate into large glandular-like structures in 3D culture [ ]. Although pluripotent stem cells can be isolated from endometrial biopsies or menstrual blood, epithelial progenitor cells cannot be obtained from menstrual blood, either because they are not present in the menstrual blood or because they are simply eclipsed by the huge amount of stromal fibroblast populations [ ]. Previous study has implied that the niche of epithelial progenitor cells is more likely to be in the basal layer than in the functional layer [, ]. In fact, epithelial progenitor cells have also been identified in the endometrial basal layer of post-menopausal women, suggesting that they may serve as a source of post-menopausal endometrial stem cells [ ].

Stage-specific embryonic antigen (SSEA)-1 is the most abundant stem cell marker found in endometrial basal glandular epithelial cells from hysterectomy tissues of women [ ]. Compared with SSEA-1 − cells, SSEA-1 + epithelial cells have significantly greater telomerase activity and longer mean telomeres, as well as more pronounced quiescence and lower proliferation rates, which are the hallmarks of epithelial progenitor cell populations.

Human endometrial epithelial progenitor cells may be a subset of the SSEA-1 + population, located in the functionalis adjoining the basalis [ ]. Leucine-rich repeat-containing G-protein-coupled receptor (LGR5) has also been detected on the rare epithelial cells in the lower functionalis adjacent to the basalis [ ]. However, the small population of endometrial LGR5 + cells has a confined capacity to form an endometrium-like structure which appears to have characteristics of resident macrophages at the perivascular microenvironment [ ]. Since macrophages are also known to exhibit stem cell properties to regulate self-replication and tissue repair [ ], LGR5 could be a marker to identify macrophages during tissue repair but not to specify epithelial progenitor cells. N-cadherin can be used to identify and isolate clonogenic and self-renewing human endometrial epithelial progenitor cells [ ]. This type of cell possesses the proliferative potential to be differentiated into cytokeratin + gland-like structures and to locate these gland-associated cells in the basalis abutting the myometrium. This finding indicates this molecule could be a novel marker for recognizing the more primitive progenitor cells that differentiate from the basalis of the endometrium.