Human organoids in basic research and clinical applications

Abstract

Organoids are three-dimensional (3D) miniature structures cultured in vitro produced from either human pluripotent stem cells (hPSCs) or adult stem cells (AdSCs) derived from healthy individuals or patients that recapitulate the cellular heterogeneity, structure, and functions of human organs. The advent of human 3D organoid systems is now possible to allow remarkably detailed observation of stem cell morphogens, maintenance and differentiation resemble primary tissues, enhancing the potential to study both human physiology and developmental stage. As they are similar to their original organs and carry human genetic information, organoids derived from patient hold great promise for biomedical research and preclinical drug testing and is currently used for personalized, regenerative medicine, gene repair and transplantation therapy. In recent decades, researchers have succeeded in generating various types of organoids mimicking in vivo organs. Herein, we provide an update on current in vitro differentiation technologies of brain, retinal, kidney, liver, lung, gastrointestinal, cardiac, vascularized and multi-lineage organoids, discuss the differences between PSC- and AdSC-derived organoids, summarize the potential applications of stem cell-derived organoids systems in the laboratory and clinic, and outline the current challenges for the application of organoids, which would deepen the understanding of mechanisms of human development and enhance further utility of organoids in basic research and clinical studies.

Somatic mosaicism in STAG2-associated cohesinopathies: Expansion of the genotypic and phenotypic spectrum

“…Morphogenesis of the brain is regulated by several Frontiers in Cell and Developmental Biology frontiersin.org complex biological pathways and the precise mechanism of abnormal forebrain development caused by loss-of-function variants in STAG2 is still unknown. Brain organoids have been introduced as promising tools to gain further insights into the impaired development of the human nervous system (Lancaster et al, 2013;Zafeiriou et al, 2020;Islam et al, 2021;Wrobel et al, 2021;Tang et al, 2022). In our recently established novel Bioengineered Neuronal Organoids (BENOs) key aspects of human brain development (Figure 5), such as neuronal network formation with demonstrated network activity (plasticity, long-and short term potentiation) could be demonstrated for the first time (Zafeiriou et al, 2020).…”

Stem cells for organoids

“…The shortcoming of ASC is that its restricted differentiation potential results in only a single epithelial cell type in all ASCderived organoids. 91 In summary, the culture techniques for generating organoids from PSCs or ASCs are still in their infancy and are highly driven by experience factors. Nowadays, efforts are being made to develop mature organoid systems.…”

Brain organoids: Establishment and application

“…Organoids often contain multiple types of organ-specific cells and can reproduce some organ functions in vitro . Compared with traditional cell models, organoid models have more stable genetic and phenotypic characteristics during in vitro culture and more abundant cell types ( Takahashi, 2019 ; Li et al, 2020 ; Tang et al, 2022 ).…”