Cancer Spheroids and Organoids as Novel Tools for Research and Therapy: State of the Art and Challenges to Guide Precision Medicine

Abstract

Spheroids and organoids are important novel players in medical and life science research. They are gradually replacing two-dimensional (2D) cell cultures. Indeed, three-dimensional (3D) cultures are closer to the in vivo reality and open promising perspectives for academic research, drug screening, and personalized medicine. A large variety of cells and tissues, including tumor cells, can be the starting material for the generation of 3D cultures, including primary tissues, stem cells, or cell lines. A panoply of methods has been developed to generate 3D structures, including spontaneous or forced cell aggregation, air–liquid interface conditions, low cell attachment supports, magnetic levitation, and scaffold-based technologies. The choice of the most appropriate method depends on (i) the origin of the tissue, (ii) the presence or absence of a disease, and (iii) the intended application. This review summarizes methods and approaches for the generation of cancer spheroids and organoids, including their advantages and limitations. We also highlight some of the challenges and unresolved issues in the field of cancer spheroids and organoids, and discuss possible therapeutic applications.

Patient‐derived organoid culture in epithelial ovarian cancers—Techniques, applications, and future perspectives

“…137,138 It was postulated that the cell aggregates could be more homogeneous, and the rotating magnetic field may also mimic the mechanical forces of blood flow. 116 Rotary cell culture systems like spinner bioreactor, rotational bioreactor, and vibrating bioreactor have been used in various cancers. 139 This method can evaluate the effects of fluid flow on cell behaviors, such as the shear stress from the flow of ascites.…”

“…However, the spheroids are mostly derived from human cancer cell lines that lack other cell populations. [114][115][116] There is a concern on the compatibility of HLA typing between the immune cells and cancer cell lines. Besides, the use of FBS may potentially interfere with the immune response in the co-culture spheroid models.…”

“…Co‐culture spheroid models have been used to study immune‐oncology. However, the spheroids are mostly derived from human cancer cell lines that lack other cell populations 114–116 . There is a concern on the compatibility of HLA typing between the immune cells and cancer cell lines.…”

“…Dynamic cell culture like magnetic levitation is an alternative way to create organoids, where cells are suspended with magnetic beads and organoids are generated under magnetic field 137,138 . It was postulated that the cell aggregates could be more homogeneous, and the rotating magnetic field may also mimic the mechanical forces of blood flow 116 . Rotary cell culture systems like spinner bioreactor, rotational bioreactor, and vibrating bioreactor have been used in various cancers 139 .…”

Trends in Photopolymerizable Bioinks for 3D Bioprinting of Tumor Models

“…Three-dimensional (3D) in vitro models are being increasingly explored to provide a more clinically relevant tumor model than 2D culture . 3D platforms comprising spheroid cultures, scaffold-based models, and organ-on-a-chip , offer various advantages to overcome some of the limitations of 2D cultures. Nevertheless, these techniques continue to be limited by their inability to efficiently recreate the full complexity of the TME with respect to spatial localization, vasculature, and architectural and dynamic complexity …”