What are Spheroids & Why do they Matter?

What are Spheroids and why do they matter?

Three-dimensional (3D) cell culture models are a potent cancer research and drug discovery tool. Although they haven’t entirely supplanted two-dimensional (2D) cell cultures in cancer studies, 3D cell cultures are advantageous for their ability to mimic in vivo cell-to-cell and cell-environment interactions. This is a direct result of their unique cellular structures. Various types of 3D cell cultures exist–including cellular scaffolds, engineered tissues, and organoids–but 3D spheroid cultures are of specific interest in cancer research. This blog post will outline the basics of spheroid formation and why they pose such promise for emerging cancer treatments.

What are Spheroids?

Spheroids are 3D clusters of cultured cells engineered to reflect both the function and structure of tumors found in vivo. Conventional 2D cell cultures are useful for numerous reasons, including their rapid proliferation and outstanding reproducibility. However, they cannot provide insight into the morphology of native structures or the cellular microenvironment. Multicellular tumor spheroids, meanwhile, accurately imitate tissue structures while preserving key molecular mechanisms. This means researchers can probe important cell-to-cell interactions and conduct critical assays–including cell invasion and cell migration.

How are Spheroids Formed?

It is important to note that spheroids are not exclusively used for cancer clinical trials and research. They can be formed from stem cells and various primary cell types–as well as cancer cells. Regardless of their composition or intended application, various 3D culturing methods can be used to generate spheroid cultures, including microfluidics in microwell plate seeding; liquid overlay; and ultra-low attachment plates. Each of these follows the general principle of self-aggregation, whereby cells agglomerate to form a 3D structure.

Why are Spheroids Important?

Significant breakthroughs in precision medicine and iterative improvements to existing cancer treatment paradigms, such as chemotherapy and immunotherapy, have highlighted the need for accurate tumor models. Anti-cancer drugs can only be effectively screened using in vitro models that accurately resemble in vivo tissues. As mentioned, the primary benefit of spheroids is their unmatched ability to mimic the tumor microenvironment–which may be composed of a single cell type or many (blood vessels, cancer cells, etc.). Research has demonstrated how tumor microenvironments are predominated by tumor-induced interactions, and that myriad different cell types can be co-opted into the site. Understanding these unique, site-specific interactions is pivotal in studying tumor progression and characterizing different cell types’ role in carcinogenesis.

Traditional cell cultures cannot reflect this complex microenvironment with any degree of reliability. 3D cell cultures, specifically spheroids, can. They can be treated with candidate drugs and observed for cell invasion, migration, viability, and so on–making them an essential part of the search for novel therapeutic technologies, including combinatorial treatments.

Is there a Downside to Spheroids?

The main problem with 3D cell culturing is its novelty. Currently, spheroid culturing is relatively complicated and occurs over a slower time period than 2D systems. Naturally, this translates into higher costs. These apparent downsides are not enough to dull the excitement surrounding 3D cell culture use in cancer studies, but it does call for pragmatism. Cell-based drug screening requires a non-destructive imaging paradigm to visualize spheroid structures over time, obtaining critical insights into cellular dynamics, apoptosis, proliferation, and so on. This allows researchers to test the viability of novel drug molecules and to identify potential drug delivery problems.

Interested in Spheroid Imaging?

At IDEA Bio-Medical, we offer various magnification options, fluorescence wavelengths, and image processing tools, such as Z-stack, de-convolution, and reconstruction, to support myriad experiments using spheroid models. We can track and record rare events within individual cells in large populations, which is extremely valuable in cancer research. 

Read More: How Spheroid Imaging Factors into Cancer Studies

Our ATHENA software enables automated spheroid analysis, rapidly identifying potential therapeutic targets through high-content screening. Contact us to learn how our imaging platforms and analysis tools can maximize the benefits of spheroid imaging for therapeutic development and cancer research.


  1. https://onlinelibrary.wiley.com/doi/10.1111/jcmm.12408
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689267/

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