The Potential Role of Organoids in Pathology and Oncology Research

Excerpt

Organoids represent a 3-dimensional, simplistic representation of an in vivo organ that is replicated in in vitro conditions. An organoid simulates the microanatomy of the organ and even retains some of the functional abilities of the organ. Organoids are generated by inducing pluripotent stem cell populations to differentiate into multiple organ-specific cell types, which in turn are conditioned to form organized tissues that model in vivo organs [1]. Organoid culture systems have been developed to form tissue structures from all three primary cell lineages. Organoids are grown in the presence of 3D cell culture media that is made using the extracellular matrix hydrogel Matrigel, which is a laminin-rich extracellular matrix that contains specific growth factors that mimic in vivo signaling. Organoid cultures have been described for a variety of tissues, including kidney, liver, pancreas, prostate, lung, brain and optic cup [2]. Organoid-based studies allow the exploration of disease pathology in the context of an entire tissue rather than in a few individual cells, as is the case in typical in vitro cell culture studies. Organoids are an ideal tool for examining the etiopathogenesis of a disease entity and for formulating therapeutic strategies [3]. A major problem in current therapeutic research is the inability to successfully translate in vitro cell culture and in vivo animal model-based therapeutic success to the success of human trials. The reason for this failure stems from the limitations of in vitro cell culture, which is unable to closely model the disease microenvironment. Although animal models can replicate the disease microenvironment, the species-specific genetic profile presents a major hurdle to the translation of these data to human trials. Thus, the use of organoids obtained from human stem cells could overcome the limitations of both the animal models and in vitro cell culture. In addition, from an ethical standpoint, in vitro-based organoid systems have greater acceptance than animal models. In the development of cancer therapeutics, apart from assessing the efficacy, optimal dosage, potential cytotoxicity, and drug interactions, the molecular basis of therapeutic resistance can be examined by comparing the mutational profiles of treatment-sensitive and treatment-resistant organoids. Based on the resulting mutational profile differences, specific mutations can be targeted to alter sensitivity towards various treatment modalities. …