Abstract

Digestive diseases have become an important source of morbidity and mortality. The considerable financial and health burdens caused by digestive diseases confirm the importance of extensive research to better understand and treat these diseases. The development of reliable preclinical models is essential for understanding the pathogenesis of digestive diseases and developing treatment and prevention methods. However, traditional established cell lines and animal models still have many limitations in the study of the digestive system. Conditional reprogramming (CR) cell culture is a newly developed primary technology that uses irradiated Swiss-3T3-J2 mouse fibroblast cells and the Rho-associated kinase (ROCK) inhibitor Y-27632 to rapidly and efficiently generate many cells from diseased and normal tissues. CR cells (CRCs) can be reprogrammed to maintain a highly proliferative state and recapitulate the histological and genomic features of the original tissue. Moreover, after removing these conditions, the phenotype was completely reversible. Therefore, CR technology may represent an ideal model to study digestive system diseases, to test drug sensitivity, to perform gene profile analysis, and to undertake xenograft research and regenerative medicine. Indeed, together with organoid cultures, CR technology has been recognized as one of the key new technologies by NIH precision oncology and also used for NCI human cancer model initiatives (HCMI) program with ATCC. In this article, we review studies that use CR technology to conduct research on diseases of the digestive system.

Highlights

  • The digestive system involves the gastrointestinal tract, including the oral cavity, pharynx, esophagus, stomach, small and large intestines, as well as auxiliary organs, namely, the liver, gallbladder, and pancreas

  • CR cells (CRCs) maintain the developmental potential of the original tissue and can restore the differentiation ability of the cells after these conditions are removed

  • Precision medicine and drug discovery Determine the important role of the MYC-ERCC3 interaction in pancreatic ductal adenocarcinoma (PDAC), found triptolide may be a potential target treatment for MYC-dependent PDAC Identify the role of the low immunogenicity anti-mesothelin immunotoxin RG7787 in pancreatic cancer Demonstrated AKT; the AKT1 pathway was activated in mucoepidermoid carcinoma (MEC), and the growth of MEC cells can be inhibited by MK2206 Identify synergistic effects of EGFR, MEK, and CDK4/6 inhibitors in the colorectal cancer Identified that ATP6V0C and IDF-11774 were synthetically lethal and this effect was associated with low B-cell CLL/lymphoma 2 (Bcl-2) expression and PIK3CA mutations For rapid screening of individualized chemotherapy for colorectal cancer patients Identified regorafenib as a potential therapeutic drug

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Summary

Introduction

The digestive system involves the gastrointestinal tract, including the oral cavity, pharynx, esophagus, stomach, small and large intestines, as well as auxiliary organs, namely, the liver, gallbladder, and pancreas. CR technology might be an ideal model to study digestive system diseases, to test drug sensitivity, to perform gene profile analysis, and in xenograft research and regenerative medicine.

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Conclusion
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