What is the Difference Between Organoids and Spheroids?

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Organoids and spheroids are both 3D cell culture models, but they differ in complexity, structure, and applications. Here are the main differences between the two:

  1. Complexity: Spheroids are spherical cellular units that are generally cultured as free-floating aggregates and are considered to be of low complexity in mirroring tumor organization. Organoids, on the other hand, are more complex structures that partially resemble the organ in both structure and function.
  2. Structure: Organoids are cells grown in 3D to form structural units that resemble the original tissue both histologically and genetically. Spheroids, however, are formed primarily via cell-to-cell adhesion, resulting in cell aggregates.
  3. Culture Methods: Spheroids can be derived from immortalized cell lines, primary cells, or fragments of human tissue. Organoids are formed using stem cells that self-renew and differentiate in vitro, driven by their self-organizing properties.
  4. Applications: Organoids are used for a wide range of applications in cancer research, including the study of carcinogenesis, drug development, and personalized medicine. Spheroids are often used in radio- and immuno-therapies to predict patient responses.
  5. Limitations: Spheroids are generally more resilient and capable of growing in vitro, which can affect drug response and produce data that poorly translates to the clinic. Organoids are considered to be more faithful recapitulations of in vivo features due to their multicellular identity and the ability of stem cells to differentiate into multiple cell types.

Comparative Table: Organoids vs Spheroids

Here is a table comparing the differences between organoids and spheroids:

Feature Spheroids Organoids
Cellular source Various cell types, including immortalized cell lines, primary cells, and tissue fragments Stem cells, which self-renew and differentiate in vitro
3D organization Spherical cellular units Structural units that partially resemble the structure and function of an organ
Organ physiology Limited More complex, mimicking the structure and function of an organ
3D culture conditions Scaffold-free system Scaffold-based system
Mechanism driving the 3D structure Cell-to-cell adhesion (i.e., cell aggregates) Self-organizing properties of stem cells
Multicellular identity Often a monoculture, lacking the multicellular identity of an in vivo environment Faithfully recapitulates the complexity of the original tissue
Drug response Tumor spheroids may have a high proportion of poorly differentiated cells, which can affect drug response More accurate drug response due to better recapitulation of in vivo features
Long-term culturing Not as suitable for long-term culturing Amenable to long-term culturing, phenotypically and genetically stable even after many passages and cryopreservation

Organoids are more complex 3D cell cultures that can mimic the structure and function of an organ, while spheroids are a simpler model system ideal for certain applications.