To Better Generate Organoids, What Can We Learn From Teratomas?

Abstract

The genomic profile of animal models is not completely matched with the genomic profile of humans, and 2D cultures do not represent the cellular heterogeneity and tissue architecture found in tissues of their origin. Derived from 3D culture systems, organoids establish a crucial bridge between 2D cell cultures and in vivo animal models. Organoids have wide and promising applications in developmental research, disease modeling, drug screening, precision therapy, and regenerative medicine. However, current organoids represent only single or partial components of a tissue, which lack blood vessels, native microenvironment, communication with near tissues, and a continuous dorsal-ventral axis within 3D culture systems. Although efforts have been made to solve these problems, unfortunately, there is no ideal method. Teratoma, which has been frequently studied in pathological conditions, was recently discovered as a new in vivo model for developmental studies. In contrast to organoids, teratomas have vascularized 3D structures and regions of complex tissue-like organization. Studies have demonstrated that teratomas can be used to mimic multilineage human development, enrich specific somatic progenitor/stem cells, and even generate brain organoids. These results provide unique opportunities to promote our understanding of the vascularization and maturation of organoids. In this review, we first summarize the basic characteristics, applications, and limitations of both organoids and teratomas and further discuss the possibility that in vivo teratoma systems can be used to promote the vascularization and maturation of organoids within an in vitro 3D culture system.

The potential of organoids in toxicologic pathology: role of toxicologic pathologists in <i>in vitro</i> chemical hepatotoxicity assessment

“…Li et al. 65 also suggested establishing guidelines for evaluating the quality and effectiveness of organoids to minimize the differences in organoids among laboratories. In humans, genetic and environmental diversity cannot be eliminated from donor-derived organoids.…”

“…3). Li et al 65 discussed several limitations in constructing human organoids, including the diversity in the nature and morphology of the organoids produced. Toxicologic pathologists are expected to actively participate in finding solutions to address the diversity of ex vivo-constructed organoids.…”

“…They are also expected to use their experience with morphological changes in a large number of normal tissues and tumors to extract organoids with morphologies appropriate for toxicity assessment and to exchange opinions with cell culture experts on how to produce organoids with specific properties more efficiently and reproducibly. Li et al 65 also suggested establishing guidelines for evaluating the quality and effectiveness of organoids to minimize the differences in organoids among laboratories. In humans, genetic and environmental diversity cannot be eliminated from donorderived organoids.…”

The Effects of Transforming Growth Factor-β1 on the Differentiation of Cell Organoids Composed of Gingiva-Derived Stem Cells

“…A previous report demonstrated that cartilaginous organoids made out of pluripotent stem cell-derived promoted the scaffold-free healing of long bone defects with critical size [ 35 ]. Furthermore, the development of blood vessels and communication with surrounding tissue can lead to greater development and more wide use of the organoids in bone regeneration [ 41 ]. The control of the coating material for the culturing dish and loading density of the cells may influence the characteristics of the organoids [ 42 ].…”

Stage Ia squamous cell carcinoma as the malignant transformation of giant and unusual mature teratoma of the ovary in an elderly patient

“…The first case of MCTO was reported by Johannes Scultetus in 1659 after the autopsy of a young woman who died of an ovarian tumor and was described as a “dermoid cyst of the ovary”, while Rudolf Virchow introduced the term “teratoma” derived from the Greek word “teras,” meaning monster, in 1863 [ 5 , 6 ]. The etiology, as well as the pathophysiology, of the MCTO, is not fully known; this is particularly true in consideration of their ability to differentiate into tissue cells and, in some cases, and they also develop into organ systems [ 7 ].…”