Organoids and spheroids are two commonly used techniques for establishing 3D cell cultures and both of them are made of multiple cells. There are several distinct differences between them.
| Basis of comparison | Organoids | Spheroids |
| Definition | Complex clusters of organ-specific cells such as those from liver, stomach or bladder | Simple clusters of broad-ranging cells such as from nervous tissue, tumor tissue, mammary glands or hepatocytes |
| Origin | Derived from a single adult stem cell or embryonic stem cell capable of self-renewing and differentiating into multiple lineages in vitro | Derived from immortalized cell lines, primary cells, or fragments of human tissue |
| Features | Often display a very accurate microanatomy | Heterogeneous, containing layers of cells with some exposed to the surface and others buried within the sphere |
Driving force for development | Internal developmental processes | Cell-to-cell adhesion |
| Scaffolding requirement | Cells self-assemble when given a scaffolding extracellular environment | Scaffolding is not required – cells assemble by simply sticking to each other |
| Representation | Multiple cell lineages | Single/partial tissue components |
| Recapitulation/resemblance | Recapitulate organ physiological parameters | Transiently resemble cell organization |
| Viability | Long term culture capable of retaining genetic features of the original organ over several generations | Difficult to maintain long term due to inherent technical difficulties in extracting and maintaining viable cells |
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