Lanford medium induces high quality hepatic lineage cell differentiation directly from mouse embryonic stem cell-derived mesendoderm

A Strategy Using Pluripotent Stem Cell-Derived Hepatocytes for Stem Cell-Based Therapies

“…Thus, the procedure for induction of hepatocyte differentiation from pluripotent stem cells consists of two steps: the first is definitive endoderm induction by activin, which acts in a similar way to Nodal, the second is hepatocyte induction by FGF and BMP-4. However, because the cells induced with this procedure are not fully maturated, we further induce maturation with serum-free Lanford medium, which is developed for maintaining human hepatocytes in vitro Yoshie et al, 2010).…”

“…Ishii et al, 2005), the hepatocytes induced using these conditions have inevitable risks, such as viral infection advising against use in possible future clinical applications. Therefore, we propose a simple two-step induction method under serum-free conditions as below (Yoshie et al, 2010). As a first step, the mesendoderm was induced by activin as shown in Fig.…”

“…The contents contain growth factors and hormone, including EGF, LCGF, prolactin insulin and glucagon (Lanford et al, 1989). It remains unknown which factors are more effective, but it is true that some of them, or all, progress maturation powerfully Yoshie et al, 2010). Drastic morphological changes had not been recognized during the periods from FGF stage to OMS, though gene expression showed signs of hepatocyte differentiation.…”

“…A lot of studies have reported the successful induction of hepatic differentiation from ESCs and iPSCs (reviewed in Andersson & Lendahl, 2009;Behbahan et al, 2011;Greenbaum, 2010;Kung & Forbes, 2009). However, undifferentiated pluripotent stem cells possess intrinsic property of teratoma formation in the host after transplantation (Fong et al, 2010;Blum & Benvenisty, 2009;Knoepfler, 2009) and their induction efficiency of hepatocellular differentiation was still not enough so that various types of cells, including undifferentiated pluripotent stem cells, remained at different stages of differentiation Shiraki et al, 2008;Teratani et al, 2005;Yoshie et al, 2010). Thus, improvement of the induction method for the hepatocellular differentiation to the efficiency of almost 100% and/or development of an efficient selection method for differentiated hepatocytes are needed.…”

Hepatic Differentiation of Human Embryonic and Induced Pluripotent Stem Cells for Regenerative Medicine

“…In this approach, using a high-density monolayer culture, pluripotent stem cells are cultured in a feeder cell-free system and mesendoderm differentiation is induced by a defined serum-free medium, supplemented with high-dose of Activin A (e.g. 100ng/ml) (Yoshie et al 2010). The signaling pathways regulating foregut formation can be recapitulated in cell culture by the addition of specific growth factors such as FGFs and BMPs.…”