Table C.

Approaches to derive transplantable hepatocytes for the treatment of genetic diseases

Approach	Strengths	Limitations	Reference
Primary hepatocyte + ex vivo gene therapy	Lifelong immunosuppression not required	Isolation of cells is challenging. Expansion requires unsafe immortalization.	Fox et al. 1995 [88]
Somatic cell →iPSC + gene correction →iHep	Simple, non-invasive isolation of somatic cells. Lifelong immunosuppression not required. Easily expandable cell population.	Possible teratoma formation. Maturity profile currently uncertain.	Si-Tayeb et al, 2010 [58] Tomizawa et al. 2013 [41] Ma et al. 2013 [57] Takayama et al. 2012 [56]
Somatic cells + gene correction→ tHep	Low tumorigenic potential. Potential for rapid, efficient, scalable production.	Maturity profile currently uncertain. More work needed to confirm feasibility for hepatocyte application.	Sekiya et al. 2011 [69] Huang et al. 2011 [67] Du et al. 2014 [66] Huang et al. 2014 [68] Simeonov et al. 2014 [70]