New Approaches in the Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells toward Hepatocytes

Behbahan, Iman Saramipoor; Duan, Yuyou; Lam, Alexander; Khoobyari, Shiva; Ma, Xiaocui; Ahuja, Tijess P.; Zern, Mark Α.

doi:10.1007/s12015-010-9216-4

Cited by 72 publications

(54 citation statements)

References 105 publications

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“…Therefore, hepatocyte transplantation has been considered as a putative alternative treatment and has attracted increasing attention, particularly in recent years with the development of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), as these cells could potentially provide an unlimited source for the generation of human hepatocytes. 1,2 In addition to hepatocyte transplantation, stem cell-derived functional human hepatocytes also have the potential to be a valuable cell source for the development of a bioartificial liver 3,4 as well as for providing an easily accessible in vitro model for determining the metabolic and toxicological properties of potential drugs in humans, a key need unmet in current pharmaceutical development. 5 Unlike transplantation, in which hepatic progenitor cells can be further differentiated in vivo, these later applications require more matured hepatocytes, which are proficient in the functions of adult liver cells, especially in their metabolic functions and toxicological responses to different drug treatments.…”

Section: Introductionmentioning

confidence: 99%

Application of Three-Dimensional Culture Conditions to Human Embryonic Stem Cell-Derived Definitive Endoderm Cells Enhances Hepatocyte Differentiation and Functionality

Ramasamy

Selden

et al. 2013

Tissue Engineering Part A

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Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) provide an unlimited source for the generation of human hepatocytes, owing to their indefinite self-renewal and pluripotent properties. Both hESC-/ iPSC-derived hepatocytes hold great promise in treating liver diseases as potential candidates for cell replacement therapies or as an in vitro platform to conduct new drug trials. It has been previously demonstrated that the initiation of hESC differentiation in monolayer cultures increases the generation of definitive endoderm (DE) and subsequently of hepatocyte differentiation. However, monolayer culture may hinder the maturation of hESC-derived hepatocytes, since such two-dimensional (2D) conditions do not accurately reflect the complex nature of threedimensional (3D) hepatocyte specification in vivo. Here, we report the sequential application of 2D and 3D culture systems to differentiate hESCs to hepatocytes. Human ESCs were initially differentiated in a monolayer culture to DE cells, which were then inoculated into Algimatrix scaffolds. Treatments of hESC-DE cells with a ROCK inhibitor before and after inoculation dramatically enhanced their survival and the formation of spheroids, which are distinct from HepG2 carcinoma cells. In comparison with monolayer culture alone, sequential 2D and 3D cultures significantly improved hepatocyte differentiation and function. Our results demonstrate that hESC-DE cells can be incorporated into Algimatrix 3D culture systems to enhance hepatocyte differentiation and function.

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Section: Introductionmentioning

confidence: 99%

Application of Three-Dimensional Culture Conditions to Human Embryonic Stem Cell-Derived Definitive Endoderm Cells Enhances Hepatocyte Differentiation and Functionality

Ramasamy

Selden

et al. 2013

Tissue Engineering Part A

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“…The cells tend to develop into a polygonal shape from spindle fibroblast morphology with the help of cytoplasm contraction (Behbahan et al 2011). The phenomena of phenotype modification are the first landmark on predicting the ability of PDLSCs to differentiate into hepatocyte-like cells.…”

Section: Discussionmentioning

confidence: 99%

Generation of functional hepatocyte-like cells from human deciduous periodontal ligament stem cells

Vasanthan

Jayaraman

Kunasekaran

et al. 2016

Sci Nat

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Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction. First phase was performed in the presence of hepatocyte growth factors to induce a definitive endoderm formation. In the subsequent phase, the cells were treated with oncostatin M and dexamethosone followed by insulin and transferrin to generate hepatocyte-like cells. Hepatic-related characters of the generated hepatocyte-like cells were determined at both mRNA and protein level followed by functional assays. Foremost changes observed in the generation of hepatocyte-like cells were the morphological features in which these cells were transformed from fibroblastic shape to polygonal shape. Temporal expression of hepatic markers ranging from early endodermal up to late markers were detected in the hepatocyte-like cells. Crucial hepatic markers such as glycogen storage, albumin, and urea secretion were also shown. These findings exhibited the ability of periodontal ligament stem cells of dental origin to be directed into hepatic lineage fate. These cells can be regarded as an alternative autologous source in the usage of stem cell-based treatment for liver diseases.

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“…Data related to the electrophysiological capacity and responsiveness of hiPSCs-derived cardiomyocytes in response to several cardiac and non-cardiac drugs have been reported [48,[63][64][65]. Thus, Cellular Dynamics International has recently commercialized hiPSCs-derived cardiomyocytes for pharmaceutical cardiotoxicity testing [66].The efficient generation of functional hepatocyte-like cells from hESCs/hiPSCs and their use for drug screening have also been reported [67]. More recently, the nervous system has started to become another area of intensive activity.…”

Section: Toxicity Screensmentioning

confidence: 99%

Human pluripotent stem cells for disease modelling and drug screening

et al. 2011

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Considerable hope surrounds the use of disease-specific pluripotent stem cells to generate models of human disease allowing exploration of pathological mechanisms and search for new treatments. Disease-specific human embryonic stem cells were the first to provide a useful source for studying certain disease states. The recent demonstration that human somatic cells, derived from readily accessible tissue such as skin or blood, can be converted to embryonic-like induced pluripotent stem cells (hiPSCs) has opened new perspectives for modelling and understanding a larger number of human pathologies. In this review, we examine the opportunities and challenges for the use of disease-specific pluripotent stem cells in disease modelling and drug screening. Progress in these areas will substantially accelerate effective application of disease-specific human pluripotent stem cells for drug screening.

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New Approaches in the Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells toward Hepatocytes

Cited by 72 publications

References 105 publications

Application of Three-Dimensional Culture Conditions to Human Embryonic Stem Cell-Derived Definitive Endoderm Cells Enhances Hepatocyte Differentiation and Functionality

Application of Three-Dimensional Culture Conditions to Human Embryonic Stem Cell-Derived Definitive Endoderm Cells Enhances Hepatocyte Differentiation and Functionality

Generation of functional hepatocyte-like cells from human deciduous periodontal ligament stem cells

Human pluripotent stem cells for disease modelling and drug screening

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