Table 1.

Summary of the advantages and disadvantages of various drug screening models.

Features	Animal	Ex vivo/biopsy tissue	Submerged in vitro culture systems		Organoid systems
			Immortalized cell lines	Primary cells	2D (ALI)	3D (spherical)	Organ-on-a-chip
Cellular complexity	Complete immune system	Localized multi-cellular responses	Lack complex multicellular interactions	Lack complex multicellular interactions	Complex multicellular interaction	Complex multicellular interaction	Complex multicellular interaction
Consistency	Biological variability	Can only be used once	Do not precisely mimic primary cells; Passage can alter functiona	Can only be used once	Inconsistent when primary cells are used	Inconsistent when primary cells are used	Hard to achieve consistency
Human specific	No	Yes, human tissues	Yes	Yes, human cells	Yes, human cells	Yes, human cells	Yes, human cells
Patient specific	No	Yes, patient specific	No	Yes	Can be using primary cells	Can be using primary cells	Can be using primary cells
Ethical approval	Required	Required with donor consent	Not needed	Required with donor consent	Only for primary cells	Only for primary cells	Only for primary cells
Ease of acquisition	Easy to obtain from vendors	Limited supplyb	Easy to obtain; Unlimited supply	Limited supplyb	Primary cells limitedc	Primary cells limitedc	Primary cells limitedc
Variability	High	High	Low	High	Depends on cell origin	Depends on cell origin	Depends on cell origin
Technical issues	Very Labor intensived	Labor intensive	Easy to use and maintain	Easy to use but variable over time	Labor intensivee	Labor intensivee	Labor intensivee
Long term mainten-ance	Yes	No	Yes	No	Yes	Yes	Yes
Cost	Expensive	Cost effective	Cost effective	Cost effective	Less expensive	Expensive	Expensive
Genetics?	Can introduce mutations	No	Yes, can mutate	Difficult	Yes	Yes	Yes

^aGenetic manipulation is required to obtain immortality of cell lines may cause altered phenotypes functions, and responses to stimuli. Passaging of cell lines can induce genotypic and/or phenotypic variations over time.

^bDonors can vary over time which contributes to difficulties to obtain cells and experimental variability.

^cThese methods can use cell lines, iPSC and ESC cells which are relatively easily obtained. Primary cells have issues with availability and donor variation.

^dRequires complex techniques and specialized facilities.

^eTechnically demanding to maintain and in the case of 3D organoids and organ on chip technically difficult to develop systems.