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Review
. 2020 Jul 16;13(1):97.
doi: 10.1186/s13045-020-00931-0.

Modeling neoplastic disease with spheroids and organoids

Michele Zanoni  1 , Michela Cortesi  2 , Alice Zamagni  2 , Chiara Arienti  2 , Sara Pignatta  2 , Anna Tesei  3
Affiliations
Review

Modeling neoplastic disease with spheroids and organoids

Michele Zanoni et al. J Hematol Oncol. .

Abstract

Cancer is a complex disease in which both genetic defects and microenvironmental components contribute to the development, progression, and metastasization of disease, representing major hurdles in the identification of more effective and safer treatment regimens for patients. Three-dimensional (3D) models are changing the paradigm of preclinical cancer research as they more closely resemble the complex tissue environment and architecture found in clinical tumors than in bidimensional (2D) cell cultures. Among 3D models, spheroids and organoids represent the most versatile and promising models in that they are capable of recapitulating the heterogeneity and pathophysiology of human cancers and of filling the gap between conventional 2D in vitro testing and animal models. Such 3D systems represent a powerful tool for studying cancer biology, enabling us to model the dynamic evolution of neoplastic disease from the early stages to metastatic dissemination and the interactions with the microenvironment. Spheroids and organoids have recently been used in the field of drug discovery and personalized medicine. The combined use of 3D models could potentially improve the robustness and reliability of preclinical research data, reducing the need for animal testing and favoring their transition to clinical practice. In this review, we summarize the recent advances in the use of these 3D systems for cancer modeling, focusing on their innovative translational applications, looking at future challenges, and comparing them with most widely used animal models.

Keywords: 3D models; Cancer; Drug discovery; Organoid; Spheroid; Tumor microenvironment.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Sarcoma 3D models. Search for articles appearing in PUBMED over the past 10 years (2009–2019) using the mesh terms “tissue scaffolds” AND “sarcoma” (green); “organoids” AND “sarcoma” (red); “spheroids, cellular” OR “spheroid” AND “sarcoma” (blue)
Fig. 2
Fig. 2
Spheroid model. a Schematic representation of spheroid variation in shape and size over time. b Main characteristics of spheroid model. The spheroid is composed of several functionally differentiated areas and layers resulting from the impaired distribution of nutrients and oxygen. Tumor cells composing the spheroids interact with each other, developing a well-organized spatial architecture characterized by differences in phenotypic, functional, and metabolic status.
Fig. 3
Fig. 3
Organoid model. Organoids currently established from healthy and cancer tissues. (References are indicated in brackets)
Fig. 4
Fig. 4
Potential research and clinical applications of organoids. Organoids derived from patients’ tumors with different subtypes and/or grading can be expanded and cryopreserved to create a living organoid biobank. Patient-derived organoids generated from tumors and healthy tissues can be genetically characterized and compared. They can also be used for personalized drug discovery and drug toxicity studies. Gene editing technologies can be used to study the role of mutational processes in the tumorigenesis in specific organs. Organoids resemble the heterogeneous cytoarchitecture found in vivo and advanced microscopy techniques can be used to follow the dynamic processes of organoid development and maturation
Fig. 5
Fig. 5
Current preclinical cancer research. 3D systems combined with new technologies such as organ-on-a-chip and 3D bioprinting could fill the gap between traditional 2D cell culture and animal models, producing more reliable data while also reducing costs, time to results, and political/ethical issues before their transition to clinical practice
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