Organoids: The current status and biomedical applications

Abstract

Organoids are three-dimensional (3D) miniaturized versions of organs or tissues that are derived from cells with stem potential and can self-organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts. Organoid culture is an emerging 3D culture technology, and organoids derived from various organs and tissues, such as the brain, lung, heart, liver, and kidney, have been generated. Compared with traditional bidimensional culture, organoid culture systems have the unique advantage of conserving parental gene expression and mutation characteristics, as well as long-term maintenance of the function and biological characteristics of the parental cells in vitro. All these features of organoids open up new opportunities for drug discovery, large-scale drug screening, and precision medicine. Another major application of organoids is disease modeling, and especially various hereditary diseases that are difficult to model in vitro have been modeled with organoids by combining genome editing technologies. Herein, we introduce the development and current advances in the organoid technology field. We focus on the applications of organoids in basic biology and clinical research, and also highlight their limitations and future perspectives. We hope that this review can provide a valuable reference for the developments and applications of organoids.

Keywords: 3D culture; drug screening; precision medicine; stem cells; tumoroid.

FIGURE 1

Strategies for formation of organoids in vitro. The cell sources for establishing organoids include embryonic stem cells (ESCs), adult stem cells (ASCs), induced pluripotent stem cells (iPSCs), and tumor cells. Resection and/or biopsy specimens from health/ patient individuals are dissociated into single cell to form organoids by incubating with various signal factors (Created with BioRender.com).

FIGURE 2

The maturation of different cell‐derived organoids. The iPSC‐derived organoids present low maturation, which are similar to the embryonic or early fetal tissues and can be used in studying organogenesis. The ESC‐derived organoids have higher maturation than iPSC‐derived organoids and are applied to model later organogenesis stage. The ASC‐derived organoids are more closely resembling adult tissue. Tumor cell‐derived organoids is a special case due to they represent adult tumor features (Created with BioRender.com).

FIGURE 3

Biomedical applications of organoids. Organoids can be used as disease models to understand the mechanisms and physiopathology of human hepatobiliary diseases. Organoids are ideal models for drug screening and toxicity assays. Patient‐derived organoids can be used to predict patient‐specific responses to drugs and personalized treatment. Additionally, cryopreservation of organoids makes the establishment of biobank possible. Other biomedical applications of organoids include biomarker discovery and regenerative medicine.

FIGURE 4

Recapitulation of tumor immune microenvironment with tumoroids. Tumor samples are obtained by resection or biopsy and dissociated into single cells to form tumoroids. Tumoroids are established from tumor cells and cocultured with autologous T cells by submerged method, which can induce the specific antitumor effects of T cells, leading to the injury and death of tumoroids. With the application of ALI method, the tumor tissues are used as the initial cell materials to generate tumoroids preserving cancer‐associated fibroblasts and immune cells, which can recapitulate the complex tumor microenvironment in vitro (Created with BioRender.com).