Noggin, Retinoids, and Fibroblast Growth Factor Regulate Hepatic or Pancreatic Fate of Human Embryonic Stem Cells

Mfopou, Josué Kunjom; Chen, Bing; Mateizel, Ileana; Sermon, Karen; Bouwens, Luc

doi:10.1053/j.gastro.2010.02.056

Cited by 148 publications

(166 citation statements)

References 41 publications

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“…However, the generation of islet cells from pancreatic progenitor cells in vitro has become the bottleneck of ESC therapy for diabetes. Thus far, a reproducible and highly efficient beta cell differentiation protocol has not yet been reported [19], which can be explained in two ways. First, the considerable genetic variation and epigenetic differences among human ESC lines can affect their propensity to differentiate into certain lineages or cell types [18].…”

Section: Discussionmentioning

confidence: 99%

CD24: A Novel Surface Marker for PDX1-Positive Pancreatic Progenitors Derived from Human Embryonic Stem Cells

et al. 2011

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Human ESCs provide a promising cell resource for the treatment of type I diabetes mellitus. Although PDX1-positive pancreatic progenitors can be efficiently generated from human ESCs by stepwise induction, further in vitro differentiation into functional, mature beta cells is not efficient or reproducible. Purification of pancreatic progenitor cells could facilitate the identification of signals that regulate beta cell differentiation and maturation. Here, we report the identification of a novel surface marker for PDX1-positive pancreatic progenitors based on an in vitro human ESC differentiation system. By costaining PDX1 and a panel of cell surface antigens at the pancreatic progenitor stage of human ESC differentiation, we discovered a positive marker, CD24. CD24-positive cells coexpressed most of the key transcription factors of pancreatic progenitors, and the expression of important pancreatic genes was greatly enriched in CD24-positive cells compared with the CD24-negative cells. In addition, CD24-positive cells could differentiate into insulin-producing cells but CD24-negative cells could not. These results indicate that CD24 could be a surface marker for PDX1-positive pancreatic progenitors derived from human ESCs. Enrichment of pancreatic progenitors with this marker will facilitate the investigation of beta cell maturation during the human ESC differentiation.

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Section: Discussionmentioning

confidence: 99%

CD24: A Novel Surface Marker for PDX1-Positive Pancreatic Progenitors Derived from Human Embryonic Stem Cells

et al. 2011

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“…Previous studies showed a high percentage (60%-80%) of hESC-differentiated cells express a panel of specific DE endodermal markers such as SOX17, FOXA2, CXCR4, and GSC, but not the visceral endodermal marker, SOX7 [15,16,25,[35][36][37] . The initiation of DE differentiation is properly induced in hESCs and hiPSCs by NODAL and WNT signals [15,18,35,38] .…”

Section: Differentiation Of Pluripotent Stem Cells Into Definitive Enmentioning

confidence: 98%

“…It is well known that DE eventually generates both pancreatic and hepatic tissues. To direct DE cells towards pancreatic differentiation in vitro, the alternative hepatic lineage differentiation is inhibited by treating the cells with different types of growth factors inhibitors, such as SU5402 (FGF receptor antagonist) and Noggin (BMP antagonist) [36] . It has been shown that BMP signaling exerts two opposite effects during pancreatic differentiation [45] .…”

Section: Differentiation Of Pluripotent Stem Cells Into Definitive Enmentioning

confidence: 99%

“…Several treatments, forskolin (an adenylate cyclase activator) and dexamethasone (a synthetic adrenocortical steroid) [28] , hepatocyte growth factor, insulin growth factor 1 and glucagon-like peptide 1 [9] , have been used to enhance pancreatic β cell maturation in vitro. Several studies have previously reported the successful production of insulin-secreting cells in vitro from either hESCs or hiPSCs [15,16,18,19,24,25,29,30,36,[58][59][60] . However these differentiated β cells showed little ability to respond to glucose, which is considered one of the well-known and important parameters that recognize functional and mature β cells.…”

Section: Differentiation Into Pancreatic β Cellsmentioning

confidence: 99%

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Advances and challenges in the differentiation of pluripotent stem cells into pancreatic β cells

Abdelalim

Emara

2015

WJSC

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Pluripotent stem cells (PSCs) are able to differentiate into several cell types, including pancreatic β cells. Differentiation of pancreatic β cells depends on certain transcription factors, which function in a coordinated way during pancreas development. The existing protocols for in vitro differentiation produce pancreatic β cells, which are not highly responsive to glucose stimulation except after their transplantation into immune-compromised mice and allowing several weeks for further differentiation to ensure the maturation of these cells in vivo . Thus, although the substantial improvement that has been made for the differentiation of induced PSCs and embryonic stem cells toward pancreatic β cells, several challenges still hindering their full generation. Here, we summarize recent advances in the differentiation of PSCs into pancreatic β cells and discuss the challenges facing their differentiation as well as the different applications of these potential PSC-derived β cells.

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“…Certaines études évaluent actuellement la possibilité d'améliorer l'oxygénation des îlots au niveau du site de transplantation. L'équipe de Shapiro a ainsi développé un système implantable en sous-cutané SYNTHÈSE REVUES Malgré les succès actuels obtenus avec les CSE, leur utilisation reste grevée de difficultés encore inextricables, comme les barrières éthiques à la généralisation de l'utilisation d'embryons humains, le manque de reproductibilité des protocoles de différenciation de lignées cellulaires de CSE [23], ou l'obtention de phénotypes divergents -en l'occurrence hépatocytaires -lors de la différenciation [24]. Les CSP induites (ou iPS) ont éga-lement leurs tares, surtout au niveau coût/efficacité et modifications épigénétiques/génétiques induites par les protocoles de reprogrammation (utilisant des facteurs de transcription oncogéniques tels que c-Myc ou Klf4 [Kruppel-like factor 4]) [25].…”

Section: Cellules Souches Pluripotentesunclassified

La thérapie cellulaire du diabète

Lysy

2016

Med Sci (Paris)

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> La poss ibilité de remplacer des cellules β déficientes par de nouvelles cellules insulinosécrétantes chez le patient diabétique est démontrée par le succès de la transplantation d'îlots pancréatiques. Le manque de donneurs cadavériques a stimulé la recherche de sources alternatives de cellules β dont le palmarès est dominé par les cellules souches pluripotentes humaines pouvant acquérir des caractéristiques quasiment identiques à celles des cellules β et rétablir l'équilibre glycémique de souris diabétiques. Néanmoins, elles comportent un risque carcinogénique actuellement inévitable. Le pancréas adulte héberge des compartiments cellulaires aux capacités de transdifférenciation établies pouvant être exploitées pharmacologiquement in situ ou via des phases d'expansion en culture. Cette revue s'intéresse aux nouveaux développements concernant la thérapie cellulaire du diabète. < vie permettent de prévenir 60 % des DT2, il n'y a, à ce jour, aucune straté-gie de prévention du DT1 et les traitements actuels ne permettent pas d'atteindre les objectifs thérapeutiques tels que révélés par le dosage de l'hémoglobine glyquée (ou glycatée) (HbA1 C ) 2 [1]. Le DT1 est donc la cible des stratégies développées pour le remplacement des cellules β qui ont vu le jour en 1966 à Minneapolis avec la première greffe de pancréas humain combinée à une greffe de rein [2]. Après plus de 47 000 greffes d'organe (pancréas associé au rein ou pancréas seul), la technique a été nettement raffinée. Elle permet actuellement une survie des greffons d'environ 85 % à 1 an post-chirurgie [3], ce qui en fait une option thérapeutique pour des patients diabétiques en insuffisance rénale [4]. Cette technique n'est malgré tout pas généralisable étant donnés les degrés de morbidité et de mortalité associés au geste chirurgical (75 % de survie à 10 ans), la nécessité d'une immunosuppression à vie, et le manque de donneurs d'organe. Ces difficultés ont stimulé la recherche pour une thérapie cellulaire du diabète fondée sur des sources cellulaires variées comme les îlots pancréatiques 3 , les cellules souches pluripotentes ou les cellules somatiques adultes du pancréas. Transplantation des îlots pancréatiquesLa transplantation des îlots de Langerhans du pancréas humain s'est développée dans les années 1970, comme une alternative moins invasive à la greffe de pancréas entier. Cette technique a bénéficié de la 2 L'hémoglobine glyquée est une forme d'hémoglobine ayant subi une glycation, c'est-à-dire une addition non enzymatique de sucre sur la protéine. C'est un marqueur de la glycémie. 3 Les îlots pancréatiques, ou îlots de Langerhans sont formés de cellules endocrines capables de synthéti-ser l'insuline, le glucagon, la somatostatine et le polypeptide pancréatique.

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Noggin, Retinoids, and Fibroblast Growth Factor Regulate Hepatic or Pancreatic Fate of Human Embryonic Stem Cells

Cited by 148 publications

References 41 publications

CD24: A Novel Surface Marker for PDX1-Positive Pancreatic Progenitors Derived from Human Embryonic Stem Cells

CD24: A Novel Surface Marker for PDX1-Positive Pancreatic Progenitors Derived from Human Embryonic Stem Cells

Advances and challenges in the differentiation of pluripotent stem cells into pancreatic β cells

La thérapie cellulaire du diabète

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