Production of hepatocyte-like cells from human pluripotent stem cells

Hannan, Nicholas R.F.; Segeritz, Charis-Patricia; Touboul, Thomas; Vallier, Ludovic

doi:10.1038/nprot.2012.153

Cited by 303 publications

(323 citation statements)

References 18 publications

(39 reference statements)

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“…developed (16). In many cases, these cells are very similar to primary hepatocytes, as judged by gene expression profiles, secreted proteins, and metabolism.…”

Section: Testing Ipscs In Animal Disease Modelsmentioning

confidence: 86%

Preclinical Studies for Induced Pluripotent Stem Cell-based Therapeutics

Harding

Mirochnitchenko

2014

Journal of Biological Chemistry

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Induced pluripotent stem cells (iPSCs) and their differentiated derivatives can potentially be applied to cell-based therapy for human diseases. The properties of iPSCs are being studied intensively both to understand the basic biology of pluripotency and cellular differentiation and to solve problems associated with therapeutic applications. Examples of specific preclinical applications summarized briefly in this minireview include the use of iPSCs to treat diseases of the liver, nervous system, eye, and heart and metabolic conditions such as diabetes. Early stage studies illustrate the potential of iPSC-derived cells and have identified several challenges that must be addressed before moving to clinical trials. These include rigorous quality control and efficient production of required cell populations, improvement of cell survival and engraftment, and development of technologies to monitor transplanted cell behavior for extended periods of time. Problems related to immune rejection, genetic instability, and tumorigenicity must be solved. Testing the efficacy of iPSC-based therapies requires further improvement of animal models precisely recapitulating human disease conditions. The breakthrough discovery that specific sets of transcription factors can reprogram cell fate and generate induced pluripotent stem cells (iPSCs) 2 from various cell types has opened many new possibilities for research on cell states, differentiation, pluripotency, and general cell identity but, most importantly, has catalyzed the development of a whole new field of regenerative medicine (1). The field is still in a relatively early stage regarding a clear understanding of underlying developmental processes, cell behavior, and biological effects after cellgrafting experiments. The use of iPSCs and their products for human applications poses many new challenges from the experimental and regulatory points of view due to the unique properties of the cells and novel mechanism of their action.

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“…developed (16). In many cases, these cells are very similar to primary hepatocytes, as judged by gene expression profiles, secreted proteins, and metabolism.…”

Section: Testing Ipscs In Animal Disease Modelsmentioning

confidence: 86%

Preclinical Studies for Induced Pluripotent Stem Cell-based Therapeutics

Harding

Mirochnitchenko

2014

Journal of Biological Chemistry

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“…Detailed information about the development of this protocol is provided in a supplemental note. In brief, iPSCs were first dissociated into single cells and induced to form endoderm spheres in response to growth factors and chemicals added to the culture according to a modified protocol (30). The endodermal spheres then formed posterior foregut-like structures when cultured in the presence of a low concentration (1%-2%) of a Matrigel scaffold that supports the formation of 3D structures from stem cells (31,32), and by addition of various concentrations of FGF10, which is known to promote the differentiation of foregut endoderm into hepatic and gallbladder cells during organogenesis (33).…”

Section: Generation Of Human Hepatic Organoids From Ipscsmentioning

confidence: 99%

Human hepatic organoids for the analysis of human genetic diseases

Guan¹,

Xu²,

Garfin³

et al. 2017

JCI Insight

176

196

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“…HLC derived from both embryonic and induced pluripotent stem cells [8][9][10] have been shown to rescue fulminant hepatic failure when transplanted into the liver of non-obese diabetic, severe combined immune-deficient (SCID) mice [9,10]. There are ethical concerns regarding the use of embryonic stem cells and there is the risk of tumorigenesis with both embryonic and induced pluripotent stem cells.…”

Section: Introductionmentioning

confidence: 99%

Hepatocyte-Like Cells Derived from Human Amniotic Epithelial Cells Can Be Encapsulated Without Loss of Viability or Function In Vitro

Vaghjiani

Vaithilingam

Saraswati

et al. 2014

Stem Cells and Development

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Placenta derived human amniotic epithelial cells (hAEC) are an attractive source of stem cells for the generation of hepatocyte-like cells (HLC) for therapeutic applications to treat liver diseases. During hAEC differentiation into HLC, they become increasingly immunogenic, which may result in immune cell-mediated rejection upon transplantation into allogeneic recipients. Placing cells within devices such as alginate microcapsules can prevent immune cell-mediated rejection. The aim of this study was to investigate the characteristics of HLC generated from hAEC and to examine the effects of encapsulation on HLC viability, gene expression, and function. hAEC were differentiated for 4 weeks and evaluated for hepatocyte-specific gene expression and function. Differentiated cells were encapsulated in barium alginate microcapsules and cultured for 7 days and the effect of encapsulation on cell viability, function, and hepatocyte related gene expression was determined. Differentiated cells performed key functions of hepatocytes including urea synthesis, drug-metabolizing cytochrome P450 (CYP)3A4 activity, indocyanine green (ICG) uptake, low-density lipoprotein (LDL) uptake, and exhibited glutathione antioxidant capacity. A number of hepatocyte-related genes involved in fat, cholesterol, bile acid synthesis, and xenobiotic metabolism were also expressed showing that the hAEC had differentiated into HLC. Upon encapsulation, the HLC remained viable for at least 7 days in culture, continued to express genes involved in fat, cholesterol, bile acid, and xenobiotic metabolism and had glutathione antioxidant capacity. CYP3A4 activity and urea synthesis by the encapsulated HLC were higher than that of monolayer HLC cultures. Functional HLC can be derived from hAEC, and HLC can be encapsulated within alginate microcapsules without losing viability or function in vitro.

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Production of hepatocyte-like cells from human pluripotent stem cells

Cited by 303 publications

References 18 publications

Preclinical Studies for Induced Pluripotent Stem Cell-based Therapeutics

Preclinical Studies for Induced Pluripotent Stem Cell-based Therapeutics

Human hepatic organoids for the analysis of human genetic diseases

Hepatocyte-Like Cells Derived from Human Amniotic Epithelial Cells Can Be Encapsulated Without Loss of Viability or Function In Vitro

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