induced hepatic stem cells (iHepSCs) are novel patient specific hepatic stem cells generated from somatic cells via direct conversion technology. SuPine Therapeutics discovered the technology for generating self-renewing and bipotent iHepSCs which show the therapeutic efficacy in liver fibrosis animal model.
Park et al., PLOS ONE (2019)
iHepSCs show cuboidal morphology and maintain the self-renewal capacity in long-term culture.
Immunostaining assay revealed that iHepSCs maintain the protein expression of hepatic stem cell markers; Epcam, Hnf4α, Afp and Ck19.
iHepSC derived hepatocytes(iHepSC-HEPs) possess the glycogen storage properties and uptake of DiI-ac-LDL into the intracellular region. Also, iHepSC-HEPs exhibit detoxification function and albumin secretion. Cholangiocyte-like cells derived from iHepSC (iHepSC-CLCs) formed branching, tubular and round cystic structures and these structures uniformly expressed cholangiocyte specific markers; CK19 and F-actin. Rhodamine123 has been used to measure the activity of Mdr1, a cholangiocyte surface glycoprotein. iHepSCs can differentiate into cholangiocyte-like cells that have typical apical-basal polarity and secretory function.
The percentage of fibrotic areas significantly decreased after iHepSC transplantation in mouse liver fibrosis model. Serum levels of alanine aminotransferase (ALT) of iHepSC-injected mice were similar to normal mice.