Organoids are organ-like clusters of cells growing in three-dimensional (3D) environment in vitro[1], [2], [3]. These cells are capable of self-renewal, self-organization, and differentiation into multiple cell types to recapitulate the structure and function of an organ in vivo[2], [3]. Organoids of retina, brain, kidney, intestine, lung, liver, pancreas, bile duct, heart, prostate, blood vessel, testis and stomach has been developed by researchers[4], [5]. Organoids offer more physiological and controllable models than traditional models, recapitulating the structure, spatial morphology, and function of organs and tissues in vivo. They act as a bridge connecting in vitro and in vivo environments.
Figure 1. Intestinal Organoids [6]
Organoids are derived from primary tissues, embryonic stem cell (ESCs), induced pluripotent stem cells (iPSCs), neonatal or adult stem cells (ASCs), or tumor tissues, cultured under defined conditions known as 3D culture system[1], [2], [3], [4], [5]. Most organoid models are developed in Matrigel and cultured in advanced media containing various growth factors[3]. ASC-derived organoids in culture typically require growth factors to mimic the signaling control of normal tissue homeostasis, such as epidermal growth factor, Noggin, and WNT3a for many of epithelial organoids[3], [5]. In contrast, ESC/iPSC-derived organoids are generated by guiding pluripotent cells through stepwise development and differentiation using various growth factors and inhibitors to recapitulate embryonic and organ-specific processes[3].
Organoids are a powerful tool for biological and clinical applications, such as development and disease modeling, precision medicine, toxicology studies, and regenerative medicine. ASCs-derived organoids closely mimic the structure and function of tissue in vivo, which is useful in modeling healthy tissue for studying homeostasis and evaluating drug safety. Using iPSCs/ESCs allows for the generation of organoids from all three germ layer[3], which is useful in developmental biology, such as studying embryogenesis and congenital diseases. Cancer organoids model tumor biology and are used in studying heterogeneity, clonal evolution, tumor–immune interactions, and drug responses.
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[1] X. Ma, Q. Wang, G. Li, H. Li, S. Xu, and D. Pang, “Cancer organoids: A platform in basic and translational research,” Genes Dis., vol. 11, no. 2, pp. 614–632, Mar. 2024, doi: 10.1016/j.gendis.2023.02.052.
[2] X.-Y. Tang et al., “Human organoids in basic research and clinical applications,” Signal Transduct. Target. Ther., vol. 7, no. 1, p. 168, May 2022, doi: 10.1038/s41392-022-01024-9.
[3] C. Corrò, L. Novellasdemunt, and V. S. W. Li, “A brief history of organoids,” Am. J. Physiol.-Cell Physiol., vol. 319, no. 1, pp. C151–C165, July 2020, doi: 10.1152/ajpcell.00120.2020.
[4] S. Yang et al., “Organoids: The current status and biomedical applications,” MedComm, vol. 4, no. 3, p. e274, June 2023, doi: 10.1002/mco2.274.
[5] Q. Yao et al., “Organoids: development and applications in disease models, drug discovery, precision medicine, and regenerative medicine,” MedComm, vol. 5, no. 10, p. e735, Oct. 2024, doi: 10.1002/mco2.735.
[6] St Johnston D (2015) The Renaissance of Developmental Biology. PLoS Biol 13(5): e1002149. https://doi.org/10.1371/journal.pbio.1002149
