Impelling force and current challenges by chemicals in somatic cell reprogramming and expansion beyond hepatocytes

Table 3 Advantages and disadvantages of different strategies for functional cell induction

Strategy	Induction efficiency	Reproducibi-lity/stability	Target specificity	Cellular function	In vivo engraftment	Safety	Scaling up	Cost	Ref.
TF-mediated pluripotent reprogramming followed by differentia-tion	Moderate	Highly reproducible/ stable	High	Immature	Low	Genomic integration; tumorigenesis risk	Expandable before differentia-tion	Very high	[11,97-99]
TF-mediated direct lineage conversion	Fast and efficient	Reproducible/stable	High	Deficient	Low	Genomic integration	Expandable in progenitors	High	[100-103]
Chemical-mediated pluripotent reprogramming followed by differentia-tion	Controversial	Poorly reproducible/ unstable	Low	Not clear	Not clear	Integration-free	Not clear	Low	[24,25,29,31]
Chemical-mediated direct lineage conversion	Low	Reproducible/ unstable	Low	Deficient	Low	Integration-free	Expandable in progenitors	Very low	[18,77,104,105]
Chemical-mediated direct lineage expansion	Fast and efficient	Reproducible/ unstable	Low	Close to primary	High	Integration free	Expandable in rodents/ Limited in humans	Very low	[62,64,67,68]

TF: Transcriptional factor; XENs: Extraembryonic endoderm-like cells.