Departament de Patologia i Terapèutica Experimental, Facultat de Medicina i Ciències de la Salut, Campus Bellvitge, Universitat de Barcelona, Barcelona, Spain.
Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Oncobell Program, CIBERONC, Barcelona, Spain.
Purinergic Signal. 2019 Jun;15(2):225-236. doi: 10.1007/s11302-019-09656-3. Epub 2019 May 23.
The human endometrium undergoes repetitive regeneration cycles in order to recover the functional layer, shed during menses. The basal layer, which remains in charge of endometrial regeneration in every cycle, contains adult stem or progenitor cells of epithelial and mesenchymal lineage. Some pathologies such as adenomyosis, in which endometrial tissue develops within the myometrium, originate from this layer. It is well known that the balance between adenosine triphosphate (ATP) and adenosine plays a crucial role in stem/progenitor cell physiology, influencing proliferation, differentiation, and migration. The extracellular levels of nucleotides and nucleosides are regulated by the ectonucleotidases, such as the nucleoside triphosphate diphosphohydrolase 2 (NTPDase2). NTPDase2 is a membrane-expressed enzyme found in cells of mesenchymal origin such as perivascular cells of different tissues and the stem cells of adult neurogenic regions. The aim of this study was to characterize the expression of NTPDase2 in human nonpathological cyclic and postmenopausic endometria and in adenomyosis. We examined proliferative, secretory, and atrophic endometria from women without endometrial pathology and also adenomyotic lesions. Importantly, we identified NTPDase2 as the first marker of basal endometrium since other stromal cell markers such as CD10 label the entire stroma. As expected, NTPDase2 was also found in adenomyotic stroma, thus becoming a convenient tracer of these lesions. We did not record any changes in the expression levels or the localization of NTPDase2 along the cycle, thus suggesting that the enzyme is not influenced by the female sex hormones like other previously studied ectoenzymes. Remarkably, NTPDase2 was expressed by the Sushi Domain containing 2 (SUSD2) endometrial mesenchymal stem cells (eMSCs) found perivascularly, rendering it useful as a cell marker to improve the isolation of eMSCs needed for regenerative medicine therapies.
为了恢复月经期间脱落的功能层，人体子宫内膜经历反复的再生循环。基底层负责每个周期的子宫内膜再生，其中包含上皮和间充质谱系的成年干细胞或祖细胞。一些病理学，如子宫内膜组织在子宫肌层内发展的腺肌病，起源于这个层。众所周知，三磷酸腺苷（ATP）和腺苷之间的平衡在干细胞/祖细胞生理学中起着至关重要的作用，影响增殖、分化和迁移。核苷酸和核苷的细胞外水平受细胞外核苷酸酶（如核苷三磷酸二磷酸水解酶 2（NTPDase2））的调节。NTPDase2 是一种膜表达的酶，存在于间质来源的细胞中，如不同组织的血管周细胞和成年神经发生区域的干细胞。本研究的目的是研究 NTPDase2 在人非病理性周期性和绝经后子宫内膜以及腺肌病中的表达。我们检查了来自无子宫内膜病理的女性的增殖、分泌和萎缩子宫内膜，以及腺肌病病变。重要的是，我们将 NTPDase2 鉴定为基底子宫内膜的第一个标志物，因为其他基质细胞标志物如 CD10 标记整个基质。正如预期的那样，NTPDase2 也存在于腺肌病基质中，因此成为这些病变的便利示踪剂。我们没有记录到 NTPDase2 在整个周期中表达水平或定位的任何变化，因此表明该酶不像其他先前研究的细胞外酶那样受女性性激素的影响。值得注意的是，Sushi Domain containing 2 (SUSD2) 子宫内膜间充质干细胞 (eMSC) 表达 NTPDase2，使其成为一种有用的细胞标志物，可用于改善再生医学治疗所需的 eMSC 分离。
