A highly proliferative mesenchymal stem/stromal cell (MSC) population was recently discovered in the dynamic, cyclically regenerating human endometrium as clonogenic stromal cells that fulfilled the International Society for Cellular Therapy (ISCT) criteria. Specific surface markers enriching for clonogenic endometrial MSC (eMSC), CD140b and CD146 co-expression, and the single marker SUSD2, showed their perivascular identity in the endometrium, including the layer which sheds during menstruation. Indeed, cells with MSC properties have been identified in menstrual fluid and commonly termed menstrual blood stem/stromal cells (MenSC). MenSC are generally retrieved from menstrual fluid as plastic adherent cells, similar to bone marrow MSC (bmMSC). While eMSC and MenSC share several biological features with bmMSC, they also show some differences in immunophenotype, proliferation and differentiation capacities. Here we review the phenotype and functions of eMSC and MenSC, with a focus on recent studies. Similar to other MSC, eMSC and MenSC exert immunomodulatory and anti-inflammatory impacts on key cells of the innate and adaptive immune system. These include macrophages, T cells and NK cells, both in vitro and in small and large animal models. These properties suggest eMSC and MenSC as additional sources of MSC for cell therapies in regenerative medicine as well as immune-mediated disorders and inflammatory diseases. Their easy acquisition via an office-based biopsy or collected from menstrual effluent makes eMSC and MenSC attractive sources of MSC for clinical applications. In preparation for clinical translation, a serum-free culture protocol was established for eMSC which includes a small molecule TGFβ receptor inhibitor that prevents spontaneous differentiation, apoptosis, senescence, maintains the clonogenic SUSD2⁺ population and enhances their potency, suggesting potential for cell-therapies and regenerative medicine. However, standardization of MenSC isolation protocols and culture conditions are major issues requiring further research to maximize their potential for clinical application. Future research will also address crucial safety aspects of eMSC and MenSC to ensure these protocols produce cell products free from tumorigenicity and toxicity. Although a wealth of data on the biological properties of eMSC and MenSC has recently been published, it will be important to address their mechanism of action in preclinical models of human disease.

最近在动态，周期性再生的人子宫内膜中发现了高度增殖的间充质干/基质细胞（MSC）群体，是满足国际细胞疗法学会（ISCT）标准的克隆性基质细胞。富集克隆性子宫内膜MSC（eMSC），CD140b和CD146共表达的特定表面标志物以及单个标志物SUSD2在子宫内膜包括月经期间脱落的层中显示出它们的血管周围身份。实际上，已经在月经液中鉴定出具有MSC特性的细胞，通常称为月经血干/基质细胞（MenSC）。MenSC通常是从月经液中以塑性粘附细胞的形式回收的，类似于骨髓MSC（bmMSC）。尽管eMSC和MenSC与bmMSC共享一些生物学特性，它们在免疫表型，增殖和分化能力上也显示出一些差异。在这里，我们回顾了eMSC和MenSC的表型和功能，重点是最近的研究。与其他MSC相似，eMSC和MenSC对先天性和适应性免疫系统的关键细胞产生免疫调节和抗炎作用。这些包括巨噬细胞，T细胞和NK细胞体外以及小型和大型动物模型。这些特性表明，eMSC和MenSC作为再生医学中细胞疗法以及免疫介导的疾病和炎性疾病的MSC的其他来源。通过基于办公室的活检或从月经液中收集它们，它们很容易获得，使eMSC和MenSC成为临床应用中有吸引力的MSC来源。在准备进行临床翻译时，为eMSC建立了无血清培养方案，其中包括小分子TGFβ受体抑制剂，该抑制剂可防止自发分化，凋亡，衰老并维持克隆性SUSD2 ⁺并增强其效能，暗示了细胞疗法和再生医学的潜力。但是，MenSC分离方案和培养条件的标准化是主要问题，需要进一步研究以最大程度地发挥其在临床中的潜力。未来的研究还将解决eMSC和MenSC的关键安全问题，以确保这些协议产生的细胞产物无致癌性和毒性。尽管最近已发布了有关eMSC和MenSC生物学特性的大量数据，但在人类疾病的临床前模型中研究它们的作用机制将非常重要。