Directed differentiation of murine-induced pluripotent stem cells to functional hepatocyte-like cells

Sancho‐Bru, Pau; Roelandt, Philip; Narain, Nidhi; Pauwelyn, Karen; Notelaers, Tineke; Shimizu, Takeshi; Ott, Michael; Verfaillie, Catherine M.

doi:10.1016/j.jhep.2010.06.014

Cited by 81 publications

(61 citation statements)

References 42 publications

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“…Fibroblasts were reprogrammed to generate iPS cells by transduction with four human reprogramming factors including Sox2, Klf4, Oct4 and c-Myc within a single lentiviral vector as previously described [11]. Post viral transduction, the cells were grown on gamma irradiation inactivated mouse embryonic fibroblasts (MEFs) feeder layer with porcine iPSCs medium (42.5% DMEM, 30% knock out DMEM [KO-DMEM], 17.5% ES FBS, 10% knock out serum replacement [KSR], 1 mM glutamine, 0.1 mM minimal non-essential amino acids, 50 U and 50 µg/ml penicillin–streptomycin, 50 µM 2-mercaptoethanol, 5 ng/ml basic fetal growth factor [bFGF], 500 U/ml mouse leukemia inhibitory factor [LIF]).…”

Section: Methodsmentioning

confidence: 99%

High Efficient Differentiation of Functional Hepatocytes from Porcine Induced Pluripotent Stem Cells

Mich-Basso

Lin

et al. 2014

PLoS ONE

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Hepatocyte transplantation is considered to be a promising therapy for patients with liver diseases. Induced pluripotent stem cells (iPSCs) provide an unlimited source for the generation of functional hepatocytes. In this study, we generated iPSCs from porcine ear fibroblasts (PEFs) by overexpressing Sox2, Klf4, Oct4, and c-Myc (SKOM), and developed a novel strategy for the efficient differentiation of hepatocyte-like cells from porcine iPSCs by following the processes of early liver development. The differentiated cells displayed the phenotypes of hepatocytes, exhibited classic hepatocyte-associated bio-functions, such as LDL uptake, glycogen storage and urea secretion, as well as possessed the metabolic activities of cytochrome P-450 (CYP) 3A and 2C. Furthermore, we compared the hepatocyte differentiation efficacy of our protocol with another published method, and the results demonstrated that our differentiation strategy could significantly improve the generation of morphological and functional hepatocyte-like cells from porcine iPSCs. In conclusion, this study establishes an efficient method for in vitro generation of functional hepatocytes from porcine iPSCs, which could represent a promising cell source for preclinical testing of cell-based therapeutics for liver failure and for pharmacological applications.

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Section: Methodsmentioning

confidence: 99%

High Efficient Differentiation of Functional Hepatocytes from Porcine Induced Pluripotent Stem Cells

Mich-Basso

Lin

et al. 2014

PLoS ONE

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“…To recapitulate the liver specification signaling based on developmental studies in the mouse and the Xenopus models (51–55), many groups including ours have used the combination of BMPs (BMP2, BMP4) and FGFs (FGF1, FGF2, FGF4, FGF8, FGF10) to specify endoderm cells generated in pluripotent stem cell cultures (17,25,27,28,35,36,40,50,56–59). Shh inhibition found in Xenopus to be required for hepatic and pancreas fate decision, has been shown to improve the generation of mESC-Hep with the use of cyclopamine (35).…”

Section: Hepatic Cell Generation From Pluripotent Stem Cells (Psc-hepmentioning

confidence: 99%

Generation of Functional Hepatic Cells from Pluripotent Stem Cells

Han

Bourdon

Hamou

et al. 2012

J Stem Cell Res Ther

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Liver diseases affect millions of people worldwide, especially in developing country. According to the American Liver Foundation, nearly 1 in every 10 Americans suffers from some form of liver disease. Even though, the liver has great ability to self-repair, in end-stage liver diseases including fibrosis, cirrhosis, and liver cancer induced by viral hepatitis and drugs, the liver regenerative capacity is exhausted. The only successful treatment for chronic liver failure is the whole liver transplantation. More recently, some clinical trials using hepatocyte transplantation have shown some clinical improvement for metabolic liver diseases and acute liver failure. However, the shortage of donor livers remains a life-threatening challenge in liver disease patients. To overcome the scarcity of donor livers, hepatocytes generated from embryonic stem cell or induced pluripotent stem cell differentiation cultures could provide an unlimited supply of such cells for transplantation. This review provides an updated summary of hepatic differentiation protocols published so far, with a characterization of the hepatic cells generated in vitro and their ability to regenerate damaged livers in vivo following transplantation in pre-clinical liver deficient mouse models.

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“…In theory, treatment with hepatic growth factors should also stimulate preferential differentiation of iPSCs of mesodermal origin to liver cells. However, attempts by Sancho-Bru et al [2011] to obtain hepatocytelike cells from murine iPSCs by directed differentiation resulted in the production of a mixture of hepatocytes and mesodermal cells displaying some characteristics of liver sinusoidal endothelium and stellate cells. Ethical limitations applied to human ESCs cannot be extended to human iPSCs since the production of human iPSCs does not involve the destruction of a human embryo [Denker, 2009].…”

Section: Developmental Potential Of Ipscsmentioning

confidence: 99%

Liver Regenerative Medicine: Advances and Challenges

Chistiakov

2012

Cells Tissues Organs

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Liver transplantation is the standard care for many end-stage liver diseases. However, donor organs are scarce and some people succumb to liver failure before a donor is found. Liver regenerative medicine is a special interdisciplinary field of medicine focused on the development of new therapies incorporating stem cells, gene therapy and engineered tissues in order to repair or replace the damaged organ. In this review we consider the emerging progress achieved in the hepatic regenerative medicine within the last decade. The review starts with the characterization of liver organogenesis, fetal and adult stem/progenitor cells. Then, applications of primary hepatocytes, embryonic and adult (mesenchymal, hematopoietic and induced pluripotent) stem cells in cell therapy of liver diseases are considered. Current advances and challenges in producing mature hepatocytes from stem/progenitor cells are discussed. A section about hepatic tissue engineering includes consideration of synthetic and natural biomaterials in engineering scaffolds, strategies and achievements in the development of 3D bioactive matrices and 3D hepatocyte cultures, liver microengineering, generating bioartificial liver and prospects for fabrication of the bioengineered liver.

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Directed differentiation of murine-induced pluripotent stem cells to functional hepatocyte-like cells

Cited by 81 publications

References 42 publications

High Efficient Differentiation of Functional Hepatocytes from Porcine Induced Pluripotent Stem Cells

High Efficient Differentiation of Functional Hepatocytes from Porcine Induced Pluripotent Stem Cells

Generation of Functional Hepatic Cells from Pluripotent Stem Cells

Liver Regenerative Medicine: Advances and Challenges

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