Technological Progress in Generation of Induced Pluripotent Stem Cells for Clinical Applications

Table 1

Methods of efficient and safe iPSCs generation for clinical applications.

Methods	Advantage	Disadvantage	Species	Efficiency (%)	Safety	References
Retroviral vectors	Dividing cell infection, moderate efficiency	Multiple integration, incomplete silencing, tumorigenicity possible	P, R, Rh, M, H	0.01~0.5	No good	[18–21]
Lentiviral vectors	Dividing or nondividing cell infection, moderate efficiency	Multiple integration, incomplete silencing, tumorigenicity possible	M, H	0.1~1	No good	[22, 23]
Induced lentiviral vectors	Tight transcriptional regulation, dividing or nondividing cell infection, moderate efficiency	Multiple integration, transactivator needed, tumorigenicity possible	P, M, H	0.1~1	No good	[24–26]
Adenoviral vectors	Nonintegration	Integrated vector-fragment possible, low efficiency	M, H	~0.001	Good	[27]
Sendaiviral vectors	Transgene decreased during cell division, nonintegration, easy to remove Sendaivirus	Integrated vector-fragment possible	H	0.001~1	Good	[28]
Plasmids	Simple transfection	Occasional integration, low efficiency	M, H	~0.001	Good	[29]
Plasmids + Nanoparticles	Rapid and simple transfection	Occasional integration, low efficiency	M	0.001~0.003	Good	[30]
oriP/EBNA-1 episomal vectors	Nonintegrating vector, long-term persistent transcription	Extremely low efficiency	H	~0.0003	Good	[31]
Cre/loxP recombination systems	Integration but excisable, dividing or nondividing cell infection	Inefficient loxP site excision, screening needed, tumorigenicity possible	H	0.1~1	No good	[32]
Piggyback transposon/transposase  system	Precise excision possible, moderate efficiency	Screening needed,	M, H	~0.1	Good	[33, 34]
Minicircle DNA episomal vectors	Improved efficiency, nonintegration	Low efficiency	H	~0.005	Good	[35]
Proteins	DNA-free	Extremely low efficiency, long-term treatment required, genetic abnormality possible	M, H	~0.001	Very good	[36, 37]
RNAs	DNA-free, High efficiency	Multiple transfection	H	~1	Very good	[38]
Factors + Small molecules	High efficiency	Long-term treatment required, abnormal signaling pathway possible, virus used	M, H	~2.05	No good	[39]

Pig (P); rat (R); rhesus monkey (Rh); mouse (M); human (H).