Improved Models of Human Endometrial Organoids Based on Hydrogels from Decellularized Endometrium.

Emilio Francés-Herrero,Hortensia Ferrero,Amparo Faus,Sara López-Martínez,Hannes Campo,Lucía De Miguel-Gómez,Antonio Pellicer,Irene Cervelló,Elena Juárez-Barber

doi:10.3390/jpm11060504

Abstract

Organoids are three-dimensional (3D) multicellular tissue models that mimic their corresponding in vivo tissue. Successful efforts have derived organoids from primary tissues such as intestine, liver, and pancreas. For human uterine endometrium, the recent generation of 3D structures from primary endometrial cells is inspiring new studies of this important tissue using precise preclinical models. To improve on these 3D models, we decellularized pig endometrium containing tissue-specific extracellular matrix and generated a hydrogel (EndoECM). Next, we derived three lines of human endometrial organoids and cultured them in optimal and suboptimal culture expansion media with or without EndoECM (0.01 mg/mL) as a soluble additive. We characterized the resultant organoids to verify their epithelial origin, long-term chromosomal stability, and stemness properties. Lastly, we determined their proliferation potential under different culture conditions using proliferation rates and immunohistochemical methods. Our results demonstrate the importance of a bioactive environment for the maintenance and proliferation of human endometrial organoids.

Highlights

The endometrium is the innermost layer of the uterus and is highly regenerative, playing a key role in supporting embryo implantation and pregnancy [1]
Human Endometrial Organoids Cultured with EndoECM Supplementation Recapitulate the In Vivo Phenotype of Endometrial Glands
While the main concern of the study was the biosuitability of porcine EndoECM for culturing human organoids, this evidence showed that organoids could develop efficiently in the presence of the matrix

Summary

Introduction

The endometrium is the innermost layer of the uterus and is highly regenerative, playing a key role in supporting embryo implantation and pregnancy [1]. Disorders affecting the endometrium typically result in infertility [2,3,4] Such disorders include endometriosis, which involves the growth of endometrial tissue outside the uterine cavity [5]; adenomyosis, the presence of endometrial glands and stroma within the myometrium [6]; Asherman’s syndrome, the presence of intrauterine and/or intracervical adhesions [7]; and endometrial atrophy, characterized by a nonproliferating endometrium [8]. These conditions are the most common infertility-causing endometrial pathologies, but their etiology is not fully understood, which hinders the development of reliable and optimized treatments. 3D culture systems are valuable emerging alternatives in the study of healthy and pathological tissues and organs

Results

Discussion

Conclusion