Successful proliferation of hepatic progenitors derived from human iPS cells
Holds promise in realization of regenerative medicine and drug screening
A group of researchers led by MIZUGUCHI Hiroyuki (Professor, Graduate School of Pharmaceutical Sciences, Osaka University, and National Institute of Biomedical Innovation) succeeded in developing a technique for the maintenance and proliferation of hepatic progenitors derived from human iPS cells. Human hepatic cells are necessary for regenerative medical techniques and drug discovery research, but obtaining a stable supply is difficult. Therefore, the use of differentiation-induced hepatic cells from human pluripotent stem cells was successfully attempted by this group.
Hepatic progenitors, adult liver precursor cells, have high proliferating ability and can be differentiated into hepatic cells in a short period of time. Therefore, if a technique for the proliferation of self-renewing hepatoblast-like cells (HBCs) --hepatic progenitors-- could be developed, when used in combination with a hepatic differentiation-inducing technique, a large number of hepatic cells could be produced. Heretofore such a technique for maintaining and proliferating HBCs derived from human iPS cells while keeping their properties had not been developed. This group was successful in developing such a technique.
Their technique will enable researchers to produce a large number of differentiation-induced hepatic cells from hPSC-derived HBCs. This group hopes their achievement will be helpful in various medical applications such as hepatocellular transplantation, drug screening, and regeneration medicine.
Abstract
The establishment of self-renewing hepatoblast-like cells (HBCs) from human pluripotent stem cells (PSCs) would realize a stable supply of hepatocyte-like cells for medical applications. However, the functional characterization of human PSC-derived HBCs was not enough. To purify and expand human PSC-derived HBCs, human PSC-derived HBCs were cultured on dishes coated with various types of human recombinant laminins (LN). Human PSC-derived HBCs attached to human laminin-111 (LN111)-coated dish via integrin alpha 6 and beta 1 and were purified and expanded by culturing on the LN111-coated dish, but not by culturing on dishes coated with other laminin isoforms. By culturing on the LN111-coated dish, human PSC-derived HBCs were maintained for more than 3 months and had the ability to differentiate into both hepatocyte-like cells and cholangiocyte-like cells. These expandable human PSC-derived HBCs would be manageable tools for drug screening, experimental platforms to elucidate mechanisms of hepatoblasts, and cell sources for hepatic regenerative therapy.
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To learn more about this research, please read the full research report entitled " Long-term self-renewal of human ES/iPS-derived hepatoblast-like cells on human Laminin 111-coated dishes " at this page of the Stem Cell Reports website.
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