2D- and 3D-Based Intestinal Stem Cell Cultures for Personalized Medicine

Abstract

Colorectal cancer (CRC) is one of the most common cancers that have high occurrence and death in both males and females. As various factors have been found to contribute to CRC development, personalized therapies are critical for efficient treatment. To achieve this purpose, the establishment of patient-derived tumor models is critical for diagnosis and drug test. The establishment of three-dimensional (3D) organoid cultures and two-dimensional (2D) monolayer cultures of patient-derived epithelial tissues is a breakthrough for expanding living materials for later use. This review provides an overview of the different types of 2D- and 3D-based intestinal stem cell cultures, their potential benefits, and the drawbacks in personalized medicine in treatment of the intestinal disorders.

Keywords: cell culture; intestinal stem cells; monolayer; organoids; personalized medicine.

Figure 1

Applications of organoid technology for drug screening and therapy in personalized medicine. Gene mutations in patients’ tissues can be identified by genome or transcriptome sequencing. Meanwhile, the biopsy materials can be cultured in Matrigel to form organoids, which can be used to establish disease models via gene editing and co-culturing with niche cells and pathogens. The modified tumor organoids can be utilized for drug screening and testing. Gene mutations in organoids can be corrected by clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9)-mediated gene editing for transplantation.

Figure 2

Models for intestinal epithelium-niche cells and epithelium–microbes/pathogen interactions. Both the 3D organoid culture and the transwell-based 2D monolayer culture can be used for the investigation of intestinal epithelium–niche cell interactions. To study the epithelium–microbe/pathogen interactions, microbes and pathogens can be introduced directly into the culture medium of 2D monolayer systems, while for the 3D cultures, pathogens need to be injected into the lumen of organoids to allow them to come into contact with the apical side of the epithelium.