Table 2 Advantages and Pitfalls of Experimental Approaches in Disease Modelling.

From: Modelling urea cycle disorders using iPSCs

Model

Pros

Cons

Primary cells121,122,123

• Conserved functional properties

• Incorporate all cell types in heterogeneous tissue

• Limited availability / limited proliferation in vitro (cell type-dependent)

• Different genotype depending on donor – lack of reproducibility

• Large variation in quality/viability

• Difficult to maintain cell functionality in vitro

• Limited genetic manipulation

Human cell lines122,123,124

• Expandable

• Similar transcriptional markers and functional properties to human primary cells

• Immortalised/proliferative

• Aneuploid

• Low clonal efficiency

• Genetic manipulation can be limited

• Batch-to-batch variations

• Reduced functional resolution

• No disease-enabling genetic background

Human adult stem cells and human foetal liver42,43,125

• Share similar properties to human primary cells

• Proliferative

• Difficult to extract

• Difficult to culture

Human induced pluripotent stem cells79,126,127

• Can differentiate into any cell type

• Easy to genetically manipulate

• Variable differentiation efficiency

• Functionally immature

• Polyhormonal cells

Organ-on-a-chip44,45,46,49

• More physiologically relevant pharmacological responses

• Models a more complex in vivo environment

• Expensive

• Cultures are challenging

Genetically modified models128,129

• In vivo

• Some anatomical and physiological similarities

• Allow proof of concept studies

• Some anatomical and physiological differences

• Can be expensive and labour intensive with larger animal models

Xenograft models15,130,131

• In vivo

• Interventions can be implemented at optimal time

• Multiple therapies can be tested on the same biopsy

• Xenograft may not be representative of the original human cells in their native state

• Results can be influenced by host’s physiology

• Suboptimal surrogate of human immune system