Organoid and Spheroid Tumor Models: Techniques and Applications.

Austin T.K. Hoke,Nyall R. London,Kenny P. Vu,Sreenivasulu Gunti

doi:10.3390/cancers13040874

Abstract

Simple SummaryCell cultures can be carried out in three dimensions (3D). Organoids and spheroids are different 3D cell culture models that can be cultured with different techniques. These 3D cell culture units established from a patient tumor have several similarities to the original tumor tissue and possess several advantages in conducting basic and clinical cancer research. Organoids prepared from a patient tissue can be preserved in a living biobank. Testing chemo-, radio- and immuno-therapies on these organoids has the potential to predict the patient responses and these models have incredible promise for personalized medicine. This review presents different organoid models, the techniques to prepare them and recent advances in their applications.Techniques to develop three-dimensional cell culture models are rapidly expanding to bridge the gap between conventional cell culture and animal models. Organoid and spheroid cultures have distinct and overlapping purposes and differ in cellular sources and protocol for establishment. Spheroids are of lower complexity structurally but are simple and popular models for drug screening. Organoids histologically and genetically resemble the original tumor from which they were derived. Ease of generation, ability for long-term culture and cryopreservation make organoids suitable for a wide range of applications. Organoids-on-chip models combine organoid methods with powerful designing and fabrication of micro-chip technology. Organoid-chip models can emulate the dynamic microenvironment of tumor pathophysiology as well as tissue–tissue interactions. In this review, we outline different tumor spheroid and organoid models and techniques to establish them. We also discuss the recent advances and applications of tumor organoids with an emphasis on tumor modeling, drug screening, personalized medicine and immunotherapy.

Highlights

Cancer represents the second most leading cause of death globally, accounting for one in six deaths according to the World Health Organization (WHO) [1]
We have summarized spheroid and organoid culture methods and their potential applications in cancer modeling, drug screening and personalized medicine
As demonstrated in recent publications, generation of organoids from different cancer types has proven to be an outstanding model for the interrogation of different phases of cancer biology and drug discovery [121]

Summary

Introduction

Cancer represents the second most leading cause of death globally, accounting for one in six deaths according to the World Health Organization (WHO) [1]. Three-dimensional (3D) cell culture models that resemble the complexity of human tumors. Oversimplified model of cancer Low success rate of establishment for some tumor types Lack of tumor heterogeneity and tumor microenvironment (TME). Spheroids are spherical cellular units that are generally cultured as freefloating aggregates and are arguably of low complexity in mirroring tumor organization. Spheroids and organoid culture models have distinct and overlapping purposes and they differ in terms of tumor cell sources, protocol for culture and the time required for establishment (Table 2). Organoids can be cultured from a very small amount of tissue and are amenable to genetic manipulations [8,9] These features allow their use for a wide range of applications in cancer research, including the study of carcinogenesis, drug development and personalized medicine. Different cell lineages that reflect the structure and function of the organ, at least in part

Spheroid Models and Methods

Organoid Methods and Models

Microfluidics and Organoid-On-A-Chip Models

Anti-Cancer Drug Screening and Gene–Drug Associations

Organoid Biobanks

Immunotherapy

Findings

Conclusions