Main differences between spheroid and organoid culture methods for ADME relevant tissues

Starting materialStem cellsFully differentiated cells
ScaffoldMostly yesMostly no
MediaComplex, often including serum, growth factors, and small moleculesOften basal and chemically defined
Time required for generation of culturesMultiple weeks3–7 days
Stability in culturesDays to few weeksWeeks to months
Main advantagesUseful to reconstruct complex architecture.
Possible to generate isogenic organoids for different tissues.
Possible to generate stem cell lines from patients with rare genotypes of interest.
Use of fully differentiated mature cells with high phenotypic relevance.
Spheroids are highly homogeneous, facilitating HTS applications.
Main disadvantagesHigh heterogeneity between organoids.
Protocols require complex differentiation regimens and culture medium compositions.
Primary mature cells are difficult to obtain.
Material is finite and cannot be expanded.
  • —, data not available; HTS, high-throughput screening.