Organoids: development and applications in disease models, drug discovery, precision medicine, and regenerative medicine

Abstract

Organoids are miniature, highly accurate representations of organs that capture the structure and unique functions of specific organs. Although the field of organoids has experienced exponential growth, driven by advances in artificial intelligence, gene editing, and bioinstrumentation, a comprehensive and accurate overview of organoid applications remains necessary. This review offers a detailed exploration of the historical origins and characteristics of various organoid types, their applications-including disease modeling, drug toxicity and efficacy assessments, precision medicine, and regenerative medicine-as well as the current challenges and future directions of organoid research. Organoids have proven instrumental in elucidating genetic cell fate in hereditary diseases, infectious diseases, metabolic disorders, and malignancies, as well as in the study of processes such as embryonic development, molecular mechanisms, and host-microbe interactions. Furthermore, the integration of organoid technology with artificial intelligence and microfluidics has significantly advanced large-scale, rapid, and cost-effective drug toxicity and efficacy assessments, thereby propelling progress in precision medicine. Finally, with the advent of high-performance materials, three-dimensional printing technology, and gene editing, organoids are also gaining prominence in the field of regenerative medicine. Our insights and predictions aim to provide valuable guidance to current researchers and to support the continued advancement of this rapidly developing field.

Keywords: animal models; disease model; drug screening organoids; personalized medicine.

FIGURE 1

Organoid construction process. (A) Chronological history of organoid establishment for each organ. From left to right in chronological order. (B) Organisms include system hierarchies from the DNA level to the entire body. (C) Model scale from cell lines to large animals such as monkeys. (D) Strategies for forming organoids in vitro. Embryonic stem cells (ESC), induced pluripotent stem cells (iPSC), and adult stem cells (AdSC) generate liver, intestine, retinal, blood vessel, brain, skin, cholangiocyte, kidney, and other organoids.

FIGURE 2

The way of engineering organoid. Engineering approaches can be applied to organoids at multiple levels. (A) Engineering the cell includes CRPISPR–Cas9, air–liquid interface, microbial injection, viral infection, and so on. (B) Engineering the microenvironment includes hydrogel, biological scaffolds, adding exogenous substances, and so on. (C) Engineering the detection method includes microfluidics, imaging analysis, and so on. (D) Engineering the cell crosstalk includes 3D bioprinting, multicellular coculture, organoid vascularization, organ‐on‐a‐chip, and so on.

FIGURE 3

Four main applications of organoids. The main applications of organoids include the construction of disease models, drug screening and toxicity assessment, precision medicine, and regenerative medicine.