Organoids: Past Learning and Future Directions.

Abstract

Preclinical medical research has historically depended on either traditional two-dimensional in vitro cell culture or animal models for the purposes of disease modeling, including cancer pathophysiology, immunology studies, drug testing, and toxicity assays. However, both of these models have intrinsic flaws. Two-dimensional cell culture systems do not capture the heterogeneity of in vivo disease, being originally derived from a limited set of cell lines. They also differ from the physiology encountered in vivo, with the majority of pharmaceutical agents, including oncology drugs which are effective in vitro failing at clinical trials. Animal models have issues of cost, associated ethical concerns, and xenogeneity comparative to human systems. Organoids are three-dimensional (3D) cell culture models derived from human tissue, which have the potential to overcome the issues with the traditional models discussed above. They self-organize into 3D structures resembling their tissue of origin and recapitulate some of its functions. They have been shown to be excellent models for the purposes of disease modeling and high-throughput drug screening, among others. Despite these benefits, some challenges yet remain in organoid research. It is hoped that the combination of organoid culture with bioengineering approaches may successfully overcome these.