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.
Highlights
The progress of clinical medicine cannot be separated from research on disease pathogenesis and drug screening
The teratoma system, as an emerging in vivo model, provides a potentially encouraging opportunity to better generate human organoids: inducing the formation of embryoid-body-like aggregates that are difficult to produce in vitro; differentiating into specific progenitor cell lineages that might increase organoid-to-organoid reproducibility; promoting vascularization that would prolong the organoid lifespan to create mature functional 3D tissues; and shortening the culture period of organoids by teratoma formation and 3D culture binding methods
To induce the differentiation of pluripotent stem cells (PSCs) in vitro, appropriate differentiation protocols should be applied according to the characteristics of each cell line because each cell line has different intrinsic differentiation potential, especially in induced pluripotent stem cells (iPSCs) (Liang and Zhang, 2013)
Summary
The progress of clinical medicine cannot be separated from research on disease pathogenesis and drug screening. Several studies showed that single specific lineage cell types, such as skeletal muscle stem cells, neural stem cells, and hematopoietic stem cells, have already been enriched from mouse PSCs through teratoma formation (Chan et al, 2018; Philipp et al, 2018; Kim et al, 2019) These enriched cells could be cultured in vitro, and even specific vascularized tissues could be isolated to generate organoids (Lee et al, 2020). The variations of cell types in teratomas could be an advantage to generate complex tissues, which provides a possibility to investigate human development at a multi-organ level All these results indicated that an in vivo teratoma system could provide a powerful platform to improve the method and technology of 3D culture. Organoid systems are changing the way scientists model organ development and expanding basic biological research and medical research into a more physiologically meaningful human environment
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