Data from: Collagen vitrigel promotes hepatocytic differentiation of induced pluripotent stem cells into functional hepatocyte-like cells

Differentiation of stem cells to hepatocytes provides an unlimited supply
of human hepatocytes and therefore has been vigorously studied. However,
to date, the stem cell-derived hepatocytes were suggested to be of
immature features. To obtain matured hepatocytes from stem cells, we
tested the effect of culturing iPS cell-derived endoderm cells on collagen
vitrigel membrane and compared with our previous reported nanofiber
matrix. We cultured hiPS cell-derived endoderm cells on a collagen
vitrigel membrane and examined the expression profiles, and tested the
activity of metabolic enzymes. Gene expression profile analysis of
hepatocytic differentiation markers revealed that upon culture on collagen
vitrigel membrane, immature markers of AFP decreased, with a concomitant
increase in the expression of mature hepatocyte transcription factors and
mature hepatocyte markers such as ALB, ASGR1. Mature markers involved in
liver functions, such as transporters, cytochrome P450 enzymes, phase II
metabolic enzymes were also upregulated. We observed the upregulation of
the liver markers for at least 2 weeks. Gene array profiling analysis
revealed that hiPS cell-derived hepatocyte-like cells (hiPS-hep) resemble
that of the primary hepatocytes. Functions of the CYP enzyme activities
were tested in multi-institution and all revealed high CYP1A, CYP2C19,
CYP2D6, CYP3A activity, which could be maintained for at least 2 weeks in
culture. Taken together, the present approach identified that collagen
vitrigel membrane provides a suitable environment for the generation of
hepatocytes from hiPS cells that resemble many characteristics of primary
human hepatocytes.