Matrix scaffolds for endometrium-derived organoid models

Abstract

The uterus-lining endometrium is essential to mammalian reproduction, receiving and accommodating the embryo for proper development. Despite its key role, mechanisms underlying endometrial biology (menstrual cycling, embryo interaction) and disease are not well understood. Its hidden location in the womb, and thereby-associated lack of suitable research models, contribute to this knowledge gap. Recently, 3D organoid models have been developed from both healthy and diseased endometrium. These organoids closely recapitulate the tissue’s epithelium phenotype and (patho)biology, including in vitro reproduction of the menstrual cycle. Typically, organoids are grown in a scaffold made of surrogate tissue extracellular matrix (ECM), with mouse tumor basement membrane extracts being the most commonly used. However, important limitations apply including their lack of standardization and xeno-derivation which strongly hinder clinical translation. Therefore, researchers are actively seeking better alternatives including fully defined matrices for faithful and efficient growth of organoids. Here, we summarize the state-of-the-art regarding matrix scaffolds to grow endometrium-derived organoids as well as more advanced organoid-based 3D models. We discuss remaining shortcomings and challenges to advance endometrial organoids toward defined and standardized tools for applications in basic research and translational/clinical fields.

Bioengineering approaches for the endometrial research and application

“…In the 21st century, several laboratories have reported the generation of human endometrial organoids by enzymatically dissociating endometrial tissue, which subsequently matures and grows into hollow spherical structures in specific media [ 28 ]. Compared with endometrial organoids derived from animal models, specific nutrients added into the human endometrial organoid culture system are different, including growth factors, hormones, and key regulators involved in signaling pathways [ 29 ].…”

“…One of the challenges that must be resolved is the use of a standardized substrate in in vitro culture systems. As summarized previously, bio-scaffold systems, including hydrogels, decellularized scaffolds, and microfluidics, display potent tailorable properties that make them versatile and attractive substrates for organoid preparation [ 28 ]. Different types of scaffold systems have been designed to fit specific cell groups, which allow for customization based on individual culture requirements and eliminate the use of a universal ECM surrogate.…”