Organoids and Colorectal Cancer

Abstract

Organoids were first established as a three-dimensional cell culture system from mouse small intestine. Subsequent development has made organoids a key system to study many human physiological and pathological processes that affect a variety of tissues and organs. In particular, organoids are becoming very useful tools to dissect colorectal cancer (CRC) by allowing the circumvention of classical problems and limitations, such as the impossibility of long-term culture of normal intestinal epithelial cells and the lack of good animal models for CRC. In this review, we describe the features and current knowledge of intestinal organoids and how they are largely contributing to our better understanding of intestinal cell biology and CRC genetics. Moreover, recent data show that organoids are appropriate systems for antitumoral drug testing and for the personalized treatment of CRC patients.

Keywords: cancer; colon; colorectal; organoids; patient-derived organoid/PDO; patient-derived tumor organoid/PDTO.

Figure 1

(a) Scheme of a colon crypt including some of the niche factors controlling cell fate. TA cells, transient-amplifying cells. Created with Biorender.com (accessed on 27 April 2021). (b) Morphology of human colon normal (PDO) and tumor (PDTO) organoids. Upper panels: light microscopy images. Middle panels: hematoxylin and eosin (H&E) staining. Lower panels: electron microscopy images showing the common undifferentiated phenotype of cells in both types of organoids (decondensed euchromatin, lack of villi, scarce cytoplasmic organella). ECM, extracellular matrix (Matrigel); L, lumen. Images shown are unpublished and correspond to studies by our group.

Figure 2

Schematic representation of the uses of normal and tumor organoids for CRC basic and clinical research. References of the original studies are shown in square brackets. Created with Biorender.com (accessed on 27 April 2021).