Endometrial Organoids: A New Model for the Research of Endometrial-Related Diseases†

Abstract

An ideal research model plays a vital role in studying the pathogenesis of a disease. At present, the most widely used endometrial disease models are cell lines and animal models. As a novel studying model, organoids have already been applied for the study of various diseases, such as disorders related to the liver, small intestine, colon, and pancreas, and have been extended to the endometrium. After a long period of exploration by predecessors, endometrial organoids (EOs) technology has gradually matured and maintained genetic and phenotypic stability after long-term expansion. Compared with cell lines and animal models, EOs have high stability and patient specificity. These not only effectively and veritably reflects the pathophysiology of a disease, but also can be used in preclinical drug screening, combined with patient derived xenografts (PDXs). Indeed, there are still many limitations for EOs. For example, the co-culture system of EOs with stromal cells, immune cell, or vascular cells are not mature, and endometrial cancer organoids have a lower success rate, which should be improved in the future. The investigators predict that EOs will play a significant role in the study of endometrium-related diseases.

Recent advances in chemically defined and tunable hydrogel platforms for organoid culture

“…Endometrium, the inner lining of the uterus, comprising epithelial and mesenchymal cells, is subjected to periodic alterations in growth, differentiation, and degradation under the influence of ovarian hormones [117]. Endometrial organoids have emerged as potential candidates for recapitulating these periodic changes and endometrium-associated pathobiological issues.…”

Capture and metabolomic analysis of the human endometrial epithelial organoid secretome

“…EEOs are heterogeneous and comprise both luminal and glandular epithelia (25,26) and more faithfully mimic in vivo phenotypes and genetics while retaining appropriate hormonal responsiveness over multiple passages (27). EEOs are, therefore, amenable to long-term expansion and can be cryopreserved (25,28,29). Interestingly, EEOs exhibit polarity, whereby apical cell membranes face the center of the organoid (inwards) while the basolateral side faces outwards (25,30,31), suggesting that EEOs could be a useful model for investigating UF formation and function in vitro.…”

The Roles of Extracellular Vesicles and Organoid Models in Female Reproductive Physiology

“…Organoids are grown from stem cells or organ progenitor cells, which are a more differentiated type of stem cell, that self-assemble and remain both genetically and phenotypically stable throughout long-term (months) culture [ 22 , 23 ] ( Figure 1 E). The generation of organoids occurs by providing cells with a specialized culture medium, containing various supplements that allow cells to multiply and self-assemble in vitro, and enables cells to proliferate in multiple layers and return to the structure and function observed in vivo [ 24 ].…”