Organoid vs. Spheroid: What's the Difference? | 3D Cell Culture | Corning

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The terms "spheroid" and "organoid" are kind of like jam or jelly.

Sure, they mean similar things, and they're often used interchangeably — most of the time, you'll get by just fine using either. But there are distinct differences between the two in how they're made and what they do.

If you're just looking to make a sandwich, either jam or jelly will do the job. But if you want to get started in complex 3D cell culture, you need to know the difference — and pick the right one.

Organoid vs. Spheroid: Learning the Basics of Cell Clusters

Spheroids and organoids are 3D structures composed of multiple cells. Each can be useful in 3D cell research — but in different ways because they're made differently.

  • Organoids are complex clusters of organ-specific cells, such as those from the stomach, liver, or bladder. They're made of stem cells or progenitor cells and self-assemble when given a scaffolding extracellular environment, such as Corning® Matrigel® matrix or collagen. When that happens, they grow into microscopic versions of parent organs viable for 3D study.
  • Spheroids are simple clusters of broad-ranging cells, such as from tumor tissue, embryoid bodies, hepatocytes, nervous tissue, or mammary glands. They don't require a scaffolding to form 3D cultures; they do so by simply sticking to each other. However, they can't self-assemble or regenerate, and thus aren't as advanced as organoids.

Organoid vs. Spheroid: Scientific Applications

Organoids and spheroids can each produce in vivo-like iterations from in vitro cultures, but they have unique applications, and different lab scenarios might call for different multicellular structures.

Organoid Applications

Organoid technology has been used to great success in personalized medicine — in disease modeling as well as optimizing drug discovery and regenerative medicine. The applications of organoids in CRISPR research could similarly help scientists better study organ development within the context of gene editing.

Specific to cancer research, 3D organoids can provide insight into the mutational signatures of selected cancers because they can mimic the pathophysiology of human tumors.

Organoids can also function as a self-assembling miniature manifestation of a parent organ, which can be of particular benefit to researchers. For example, neural organoids bring us closer to understanding diseases in the brain, while researchers have studied intestinal organoids to better understand cystic fibrosis.

Spheroid Applications

Perhaps most notably, tumor spheroids can help scientists understand the in vivo microenvironments of tumors, which can help researchers predict drug efficacy in cancer research. The earliest iterations of spheroids were developed in the 1970s to study the impact of radiotherapy on human tumor cells.

Spheroids can also be used in stem cell research to develop embryoid bodies from induced pluripotent stem cells, which can then be turned into high-purity neural stem cells useful in studying neural diseases and their related treatments.

Scientists have also used tumor spheroids to study the cytotoxic effects of CAR-T cells — such as with the KILR® Cytotoxicity assay developed by DiscoverX. When CAR-T cells are grown in KILR-transduced tumor spheroids, scientists can form, culture, and assay on the same spheroid microplate.

Making 3D Models Work for You

Whichever structure suits your needs, spheroids and organoids can unlock greater insights for cell research in ways 2D studies simply can't. As research continues, the field is primed for even greater success — which means more opportunities to tap into the growing power of 3D research.

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