Conditional Cell Reprogramming in Modeling Digestive System Diseases

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.

Medicinal plants used for gastrointestinal disorders in Morocco

“…Digestive disorders vary depending on the organ affected. Indeed, mortality due to these diseases has increased considerably in recent years (Tangjitman et al 2015, Zhao et al 2021. Among many gastrointestinal disorders, ulcerative colitis, Crohn's disease, functional dyspepsia, diverticular disease, irritable bowel syndrome and acid reflux are the most common serious illnesses (Bajgai et al 2022).…”

G Protein-Coupled Receptor GPR35 Suppresses Lipid Accumulation in Hepatocytes

“… 23 This is routinely linked to the regulation of Rho-kinases and hence the actin cytoskeleton of cells. 22 Although there are no direct small-molecule inhibitors of Gα 13 , treatment with the Rho-kinase inhibitor Y27632 27 , 28 all but eliminated the response to lodoxamide ( Figure 2 B).…”

Conditional Reprogramming Modeling of Bladder Cancer for Clinical Translation

“…These characteristics qualified CR as an outstanding in vitro model compared to other models, such as organoids and patient-derived xenograft [ 44 ]. Applications of CR technology in clinical research have been studied in prostate [ 49 ], bladder [ 53 ], breast [ 54 ], lung [ 55 ], liver [ 56 ], and gastric [ 57 ] cancers. The CR system is applicable to many epithelial tissues including prostate, kidney, skin, and lung, among many others [ 45 ].…”