Cellular models for human cardiomyopathy: What is the best option?

Table 1 Comparison between animal and cell models

Properties	Animal	Cellular
Maintain genetic background	No	Yes
Cost of maintenance	Expensive	Less Expensive
Ease of maintenance	Simple	Difficult
Time required	+++	+
Drug effects	Potentially not translatable	Translatable
Study of paracrine effects	Yes	No
Study of circulatory effects	Yes	No

Table 2 Methods of delivery for reprogramming factors

Method	Advantages	Disadvantages
Retroviral transduction	Efficient, validated for multiple cell types, easy	Transgene integration
Lentiviral delivery	Very efficient	Transgene integration
Adenoviral transduction	Does not integrate	Low efficiency, only validated for fibroblasts
Plasmid DNA transfer (episomal)	Good efficiency, does not integrate, able to replicate autonomously, validated for multiple cell types	Low efficiency in fibroblast reprogramming
Lox p lentivirus delivery	High efficiency, excision of the integrated sequence, gene expression profile closer to hES cells	Genomic instability and genome rearrangements and loxP site remains integrated
Sendai virus	Efficient, does not integrate, validated for multiple cell types	Cost if purchased commercially or challenging if generated by a laboratory
PiggyBAC transposon	Efficient, precise and efficient self-excision, does not remain integrated	Published work only in fibroblasts, licensing patent issues, pBt gene may remain active post-transposition
Polyarginine tagged polypeptide	Does not integrate	Low efficiency, time-consuming, technically challenging and work only on fibroblasts
RNA modified synthetic mRNA	Very efficient, does not integrate, factor available commercially	Cost if purchased commercially or challenging if generated by a laboratory and work only on fibroblasts

Table 3 Advantages and disadvantages of different cell types for modeling disease in vitro

Properties	Fibroblasts	iPSCs
Proliferation capacity	+	++
Self-renewal	No	Yes
Longevity	Limited	Unlimited
Differentiation	No	Yes
Metabolism	Quiescent	Energetic
Acquisition	Easy	Difficult
Cost	+	+++
Ease of maintenance	Simple	Difficult
Necessary expertise	Low	High
Disease modeling	+	++
Structure	Single elongated cells	Round colonies/beating CM sheets
Maturation	Not applicable	Required for CM

iPSCs: Induced pluripotent stem cells; CM: Cardiomyopathy.