The evolution from 2D monolayer cultures towards 3D cell cultures has marked a crucial advance for modelling human development and diseases. Since the landmark study by Sato et al. in 2009, the development of 3D structures has evolved, giving rise to different types of organoids and spheroids. Sometimes, these terms get mixed up, leading to misunderstandings between researchers.
To facilitate effective scientific communication, there is a need for consistent terminology. A panel of experts has revisited the concept of an organoid and introduced an intuitive classification system and terminology for describing 3D structures.
Is it an organoid or a spheroid?
Although both are 3D structures, there are 3 main differences to distinguish them:
1. 3D organisation. Organoids are three-dimensional structures derived from stem cells, progenitors, or differentiated cells that self-organise to recapitulate aspects of the native tissue architecture and function, resembling mini-organs. They are usually composed of diverse cell types, including cells from diverse germ layers (multi-tissue organoids or multi-organ organoids).
Spheroids are compact, rounded spheres (although other shapes are possible), typically consisting of only one cell type. They show lower structural complexity compared to organoids.
2. Culture conditions. Organoids self-organise when placed in a matrix-rich 3D environment, such as Matrigel; they require cell-matrix interactions and specific growth factors. Nevertheless, spheroids form in the absence of a predefined culture substrate to adhere to. Standard generating techniques include hanging-drop and ultra-low attachment cultures, encouraging cell-cell interaction.
3. Culture timing. Regarding their culture, there are two main differences. Although spheroids are more straightforward to culture and form in 2-3 days, they are challenging to maintain over time. On the contrary, organoids are more complex to establish, up to 3 weeks, but their self-renewal capacity allows them to be cultured for several months.
Organoids vs spheroids: applications in biomedicine
Spheroids and organoids are both 3D cell culture models used in biomedical research, but they have distinct characteristics and applications due to their differences in complexity and functionality.
Spheroids are widely used in drug screening and toxicity testing; they are technically less challenging and cost-effective to generate many samples, allowing high-content screening to test new drugs in preclinical stages. Moreover, they can mimic the 3D structure of tumours, making them helpful in evaluating the efficacy and toxicity of anticancer drugs. This ability to replicate some aspects of solid tumours allows us to study tumour growth, invasion, and tumour microenvironment.
Organoids are more complex structures and better replicate the complexity of an organ, histologically and genetically. In addition, organoids can be cultured from a very small amount of tissue and are amenable to genetic manipulations. These features allow their use for disease modelling by deriving organoids from patients’ cells, allowing the study of disease mechanisms, genetic disorders, and the development of personalised medicine approaches. They provide a more accurate model for testing drug responses and tailoring treatments to individual patients.
The choice between spheroids and organoids depends on the specific research goals and the complexity of the studied biological systems.
BeCytes hepatic cells are 3D-qualified
At BeCytes, they specialise in cell isolation and its characterisation for research purposes. Their primary human hepatocytes have been isolated from healthy and pathological donor livers and retain important characteristics of liver cells found in the human body.
All their cell lots are properly characterised, including their ability to form spheroids. BeCytes lots tested positively for 3D culture are labeled as 3D/Spheroid Qualified.
References
Gunti S, Hoke ATK, Vu KP, London NR Jr. Organoid and Spheroid Tumor Models: Techniques and Applications. Cancers (Basel). 2021 Feb 19;13(4):874.
Hu Y, Hu X, Luo J, Huang J, Sun Y, Li H, Qiao Y, Wu H, Li J, Zhou L, Zheng S. Liver organoid culture methods. Cell Biosci. 2023 Nov 1;13(1):197.
Marsee A, Roos FJM, Verstegen MMA; HPB Organoid Consortium; Gehart H, de Koning E, Lemaigre F, Forbes SJ, Peng WC, Huch M, Takebe T, Vallier L, Clevers H, van der Laan LJW, Spee B. Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids. Cell Stem Cell. 2021 May 6;28(5):816-832.
Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009 May 14;459(7244):262-5.
Originally posted by BeCytes Biotechnologies on: https://becytes.com/organoids-vs-spheroids-3-important-differences/
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