Erratum: Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development

Touboul, Thomas; Hannan, Nicholas R.F.; Corbineau, Sébastien; Martinez, Amélie; Martinet, Clémence; Branchereau, Sophie; Mainot, Sylvie; Strick‐Marchand, Hélène; Pedersen, Roger A.; Santo, James P. Di; Weber, Anne; Vallier, Ludovic

doi:10.1002/hep.23752

Cited by 4 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hepatic Differentiation of hESCs : Hepatic induction media were chosen according to previous studies and optimized slightly. At the beginning of differentiation (day 0), surface membrane of the stencil was removed to leave behind monolayered hESCs arrays.…”

Section: Methodsmentioning

confidence: 99%

“…Various differentiation strategies have been explored, most of which aim to simulate in vivo liver development through three derivative stages, namely definitive endoderm differentiation, hepatocyte progenitor specification and hepatocyte maturation. Cytokines such as Activin A, Wnt3a, BMP2/4, FGF2/4, hepatocyte growth factor (HGF), oncostatin M (OSM) have been supplemented into the induction media of pluripotent colonies or attached cultures after EBs formation . Besides cytokines, genetic/epigenetic modification, co‐culture and modulation of ECM substrates have been proved to promote hESCs differentiation towards hepatic lineage …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hepatic Differentiation of Human Embryonic Stem Cells as Microscaled Multilayered Colonies Leading to Enhanced Homogeneity and Maturation

Yao

Wang

et al. 2014

Small

View full text Add to dashboard Cite

Directed differentiation of human embryonic stem cells (hESCs) towards hepatocyte-like cells on planar tissue culture plates has been extensively investigated with great promise to provide alternative cell sources for drug metabolism/toxicity testing. Recently, hepatic differentiation of hESCs in 3D configuration with better mimicry of embryonic liver development represents incremental efforts to improve the differentiation efficiency and cellular maturation. However, most of the present 3D differentiation configurations involved interruptive operations during the multi-staged differentiation process, which might impose unwanted influence on cellular differentiation. Most of the current researches resulted in generation of hepatocytes with high expression of AFP, which is minimally expressed in primary hepatocytes. Here, off-the-shelf micro-stencil arrays are developed to generate adherent multilayered colonies composed of hESCs-derived cells. Uninterrupted cellular differentiation and proliferation is achieved to recapitulate the continuous and multi-stage liver development. Compared with conventional 2D format, the micro-scaled multilayered colonies with uniform and defined sizes constrained within the microwells are composed of more homogenous and mature hepatocyte-like cells with significantly lowered AFP expression and elevated hepatic functions. The multilayered colonies as novel 3D configuration for hepatic differentiation of hESCs represent a significant step toward efficient generation of functional hepatocytes for regenerative medicine and drug discovery.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hepatic Differentiation of Human Embryonic Stem Cells as Microscaled Multilayered Colonies Leading to Enhanced Homogeneity and Maturation

Yao

Wang

et al. 2014

Small

View full text Add to dashboard Cite

show abstract

Cellules souches embryonnaires humaines et iPS

2010

Self Cite

View full text Add to dashboard Cite

Le foie est le siège de nombreux déficits métaboli-ques (maladies du cycle de l'urée, hypercholestéro-lémie familiale, syndrome de Crigler-Najjar type I, etc.), mais aussi la cible d'atteintes hépatiques chroniques ou aiguës. Actuellement la transplantation > La transplantation d'hépatocytes est considérée comme une alternative à la transplantation d'organes pour le traitement de maladies métaboliques notamment. Cependant, en raison des difficultés de disposer d'un grand nombre d'hépatocytes, de nouvelles sources de cellules ont été envisagées. Ces cellules peuvent être d'origine hépatique (cellules souches hépatiques) ou extra-hépatique, telles les cellules souches mésenchymateuses ou les cellules souches pluripotentes (cellules souches embryonnaires humaines [CSEh] ou iPS). Nous avons mis au point une méthode de diffé-renciation des CSEh en hépatocytes foetaux. Les conditions de différenciation qui reproduisent les étapes majeures du développement embryonnaire du foie sont établies en milieu défini, sans ajout de produit d'origine animale ou indéterminée. Les cellules obtenues expriment de nombreux marqueurs d'hépatocytes foetaux (cytochrome p450 3A7, albumine, alpha-1-antitrypsine, etc.). Elles sont capables d'assurer des fonctions spécifiques des hépatocytes (métaboliser l'ammonium, excré-ter le vert d'indocyanine), et enfin de se dévelop-per et d'exprimer des protéines hépatiques deux mois après transplantation dans le foie de souris nouveau-nés immunodéficientes (uPAxrag2gc -/-). Nous avons également démontré que ce protocole s'appliquait également aux iPS, et les études dans les modèles animaux nous permettront de comparer le potentiel in vivo de ces deux sources de cellules pluripotentes. Seules des approches précliniques effectuées chez le primate permettront de valider une éventuelle application à l'homme. < ortho topique est le seul traitement curatif des maladies métaboliques sévères engageant le pronostic vital mais elle est restreinte par la pénurie croissante de donneurs d'organe. La thérapie cellulaire apparaît depuis quelques années comme une alternative thérapeutique pour le traitement de ces maladies. En effet, elle permettrait de remplacer les seuls hépatocytes porteurs d'un défaut génétique, en laissant intact le foie. L'obstacle majeur de cette approche est que les hépatocytes ne peuvent pas être amplifiés en culture et résistent mal à la congélation. Il est donc nécessaire d'évaluer le potentiel d'autres sources de cellules, qui non seulement pourraient se différencier en hépatocytes mais aussi proliférer in vitro. Ces deux propriétés caractérisent les cellules souches pluripotentes, et en particulier les cellules souches embryonnaires et les iPS (induced pluripotent stem cells). Nous faisons le point dans cette revue sur les progrès réalisés dans l'obtention d'hépatocytes fonctionnels à partir de cellules souches pluripotentes en nous fondant sur l'expérience de notre équipe dans ce domaine.

show abstract

Stimulation of Cultured H9 Human Embryonic Stem Cells with Thyroid Stimulating Hormone Does Not Lead to Formation of Thyroid-Like Cells

Onyshchenko

Panyutin

et al. 2012

Stem Cells International

View full text Add to dashboard Cite

The sodium-iodine symporter (NIS) is expressed on the cell membrane of many thyroid cancer cells, and is responsible for the radioactive iodine accumulation. However, treatment of anaplastic thyroid cancer is ineffective due to the low expression of NIS on cell membranes of these tumor cells. Human embryonic stem cells (ESCs) provide a potential vehicle to study the mechanisms of NIS expression regulation during differentiation. Human ESCs were maintained on feeder-independent culture conditions. RT-qPCR and immunocytochemistry were used to study differentiation marker expression, 125I uptake to study NIS function. We designed a two-step protocol for human ESC differentiation into thyroid-like cells, as was previously done for mouse embryonic stem cells. First, we obtained definitive endoderm from human ESCs. Second, we directed differentiation of definitive endoderm cells into thyroid-like cells using various factors, with thyroid stimulating hormone (TSH) as the main differentiating factor. Expression of pluripotency, endoderm and thyroid markers and 125I uptake were monitored throughout the differentiation steps. These approaches did not result in efficient induction of thyroid-like cells. We conclude that differentiation of human ESCs into thyroid cells cannot be induced by TSH media supplementation alone and most likely involves complicated developmental patterns that are yet to be understood.

show abstract

Erratum: Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development

Cited by 4 publications

References 0 publications

Hepatic Differentiation of Human Embryonic Stem Cells as Microscaled Multilayered Colonies Leading to Enhanced Homogeneity and Maturation

Hepatic Differentiation of Human Embryonic Stem Cells as Microscaled Multilayered Colonies Leading to Enhanced Homogeneity and Maturation

Cellules souches embryonnaires humaines et iPS

Stimulation of Cultured H9 Human Embryonic Stem Cells with Thyroid Stimulating Hormone Does Not Lead to Formation of Thyroid-Like Cells

Contact Info

Product

Resources

About