Next-Generation Stem Cell Therapy

induced hepatic stem cells (iHepSC)

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)

Characteristics and Functionality
Generation of self-renewing iHepSC

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.

Bipotential capacity of iHepSCs into hepatocytes and cholangiocytes

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.

Therapeutic effects of iHepSCs on liver fibrosis model

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.