BACKGROUND & AIMS: Induced pluripotent stem (iPS) cells exert phenotypic and functional characteristics of embryonic stem cells even though the gene expression pattern is not completely identical. Therefore, it is important to develop procedures which are specifically oriented to induce iPS cell differentiation. METHODS: In this study, we describe the differentiation of mouse iPS cells to hepatocyte-like cells, following a directed differentiation procedure that mimics embryonic and fetal liver development. The sequential differentiation was monitored by real-time PCR, immunostaining, and functional assays. RESULTS: By sequential stimulation with cytokines known to play a role in liver development, iPS cells were specified to primitive streak/mesendoderm/definitive endoderm. They were then differentiated into two types of cells: those with hepatoblast features and those with hepatocyte characteristics. Differentiated hepatocyte-like cells showed functional properties of hepatocytes, such as albumin secretion, glycogen storage, urea production, and inducible cytochrome activity. Aside from hepatocyte-like cells, mesodermal cells displaying some characteristics of liver sinusoidal endothelium and stellate cells were also detected. CONCLUSIONS: These data demonstrate that a protocol, modeled on embryonic liver development, can induce hepatic differentiation of mouse iPS cells, generating a population of cells with mature hepatic phenotype.
BACKGROUND & AIMS: Induced pluripotent stem (iPS) cells exert phenotypic and functional characteristics of embryonic stem cells even though the gene expression pattern is not completely identical. Therefore, it is important to develop procedures which are specifically oriented to induce iPS cell differentiation. METHODS: In this study, we describe the differentiation of mouse iPS cells to hepatocyte-like cells, following a directed differentiation procedure that mimics embryonic and fetal liver development. The sequential differentiation was monitored by real-time PCR, immunostaining, and functional assays. RESULTS: By sequential stimulation with cytokines known to play a role in liver development, iPS cells were specified to primitive streak/mesendoderm/definitive endoderm. They were then differentiated into two types of cells: those with hepatoblast features and those with hepatocyte characteristics. Differentiated hepatocyte-like cells showed functional properties of hepatocytes, such as albumin secretion, glycogen storage, urea production, and inducible cytochrome activity. Aside from hepatocyte-like cells, mesodermal cells displaying some characteristics of liver sinusoidal endothelium and stellate cells were also detected. CONCLUSIONS: These data demonstrate that a protocol, modeled on embryonic liver development, can induce hepatic differentiation of mouse iPS cells, generating a population of cells with mature hepatic phenotype.
Authors: Ravali Raju; David Chau; Tineke Notelaers; Chad L Myers; Catherine M Verfaillie; Wei-Shou Hu Journal: Stem Cells Dev Date: 2018-05-31 Impact factor: 3.272
Authors: Philip Roelandt; Karen Ann Pauwelyn; Pau Sancho-Bru; Kartik Subramanian; Bipasha Bose; Laura Ordovas; Kim Vanuytsel; Martine Geraerts; Meri Firpo; Rita De Vos; Johan Fevery; Frederik Nevens; Wei-Shou Hu; Catherine M Verfaillie Journal: PLoS One Date: 2010-08-11 Impact factor: 3.240
Authors: Yue Yu; Hongling Liu; Yasuhiro Ikeda; Bruce P Amiot; Piero Rinaldo; Stephen A Duncan; Scott L Nyberg Journal: Stem Cell Res Date: 2012-06-28 Impact factor: 2.020