Portal de Periódicos da CAPES

Effects of a small molecule R-spondin-1 substitute RS-246204 on a mouse intestinal organoid culture

2017; Impact Journals LLC; Volume: 9; Issue: 5 Linguagem: Inglês

10.18632/oncotarget.23721

1949-2553

Myeong-Ok Nam, Soojung Hahn, Joo Hyun Jee, Tae-Sun Hwang, Ho Sung Yoon, Dong Hyeon Lee, Min‐Soo Kwon, Jongman Yoo,

Cancer Research and Treatments

// Myeong-Ok Nam 1, 2 , Soojung Hahn 1, 2 , Joo Hyun Jee 1, 2 , Tae-Sun Hwang 2, 3 , Ho Yoon 2, 3 , Dong Hyeon Lee 2, 4 , Min-Soo Kwon 2, 5 and Jongman Yoo 1, 2 1 Department of Microbiology and School of Medicine, CHA University, Seongnam-si, Gyeonggi-do 13488, South Korea 2 Institute of Basic Medical Sciences, School of Medicine, CHA University, Seongnam-si, Gyeonggi-do 13488, South Korea 3 Department of Anatomy, School of Medicine, CHA University, Seongnam-si, Gyeonggi-do 13488, South Korea 4 Department of Physiology, School of Medicine, CHA University, Seongnam-si, Gyeonggi-do 13488, South Korea 5 Department of Pharmacology, School of Medicine, CHA University, Seongnam-si, Gyeonggi-do 13488, South Korea Correspondence to: Jongman Yoo, email: jongmanyoo@cha.ac.kr Keywords: intestinal organoid; enteroid; R-spondin-1; RS-246204: Lgr5 Received: September 26, 2017 Accepted: December 05, 2017 Published: December 26, 2017 ABSTRACT Organoids, a multi-cellular and organ-like structure cultured in vitro , can be used in a variety of fields such as disease modeling, drug discovery, or cell therapy development. When organoids derived from Lgr5 stem cells are cultured ex vivo , recombinant R-spondin-1 protein should be added at a high concentration for the initiation and maintenance of the organoids. Because the addition of large amounts of R-spondin-1 greatly increases the cost of organoids, the organoids grown with R-spondin-1 are not practical for large-scale drug screening and for the development of therapeutic agents. In this study, we tried to find a R-spondin-1 substitute compound that is able initiate small intestinal organoids without the use of the R-spondin-1 protein; thus, using organoid media that each included one compound from among an 8,364 compound library instead of R-spondin-1, we observed whether organoids were established from the crypts of the small intestine. As a result, we found one compound that could promote the initial formation and growth of enteroids in the medium without R-spondin-1 and named it RS-246204. The enteroids grown with RS-246204 had a similar differentiation capacity as well as self-renewal capacity as the enteroids grown with R-spondin-1. Furthermore, the RS-246204-derived enteroids could successfully produce the forskolin induced swelling and the organoid based epithelial to mesenchymal transition model. This compound could be used for developing a cost-efficient culturing method for intestinal organoids as well as for exploring Lgr5 signaling, intestinal stem cell physiology and therapeutics for GI tract diseases.