Liver‐Stage Development of<i>Plasmodium falciparum,</i>in a Humanized Mouse Model

Morosan, Serban; Hez-Deroubaix, Stéphanie; Lunel, F.; Rénia, Laurent; Giannini, Carlo; Rooijen, Nico van; Battaglia, Sérena; Blanc, Catherine; Eling, W.M.C.; Sauerwein, Robert W.; Hannoun, L.; Belghiti, Jacques; Bréchot, Christian; Kremsdorf, Dina; Druilhe, Pierre

doi:10.1086/500840

Cited by 102 publications

(82 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…19 To control nonadaptive defense, mice were treated as described. 20 The uPA/SCID mice were killed 6 weeks after transplantation. Blood samples were collected, and livers were removed.…”

Section: Methodsmentioning

confidence: 99%

Transdifferentiation of hepatocyte‐like cells from the human hepatoma HepaRG cell line through bipotent progenitor†

et al. 2007

Self Cite

View full text Add to dashboard Cite

Hepatic tumors, exhibiting mature hepatocytes and undifferentiated cells merging with cholangiocyte and hepatocyte phenotypes, are frequently described. The mechanisms by which they occur remain unclear. We report differentiation and transdifferentiation behaviors of human HepaRG cells isolated from a differentiated tumor developed consecutively to chronic HCV infection. We demonstrate that, in vitro, proliferating HepaRG cells differentiate toward hepatocyte-like and biliary-like cells at confluence. If hepatocyte-like cells are selectively isolated and cultured at high cell density, they proliferate and preserve their differentiation status. However, when plated at low density, they transdifferentiate into hepatocytic and biliary lineages through a bipotent progenitor. In accordance, transplantation of either undifferentiated or differentiated HepaRG cells in uPA/SCID mouse damaged liver gives rise mainly to functional human hepatocytes infiltrating mouse parenchyma. Analysis of the differentiation/transdifferentiation process reveals that: (1) H epatic tumors with combined hepatocellular cholangiocarcinoma have been frequently described for instance, hepatoblastoma with cholangioblastic features in young patients 1 and HCCs with dual expression of hepatocyte and bile duct markers in adult patients suffering from diseases related to HCV and/or HBV infection. 2 Such tumors usually contain mature hepatocytes and so-called transitional areas that consist of undifferentiated cells that have morphological and immunological features of both hepatocytes and cholangiocytes. 3 Co-expression of hepatocytic and biliary markers suggests involvement of hepatic progenitor cells in development of these human tumors and supports the concept of genetic events to explain their abnormal growth during tumor formation. 4 However, mechanisms of occurrence of these progenitors and abnormal control of their expansion and differentiation are still unclear.Hepatic progenitor cells, also referred to as oval cells in rodents, have been defined as immature epithelial cells able to differentiate toward both biliary and hepatocytic lineages. The smallest ramification of the biliary tree in adult liver, the canal of Hering, may constitute the niche for these hepatic progenitor cells. 5 They are few in number, and because bile ductular and hepatocytic cells have a tremendous capacity to proliferate and differentiate, heAbbreviations: BrdU, bromodeoxyuridine; HNF, hepatocyte nuclear factor; RT, reverse transcription.

show abstract

“…19 To control nonadaptive defense, mice were treated as described. 20 The uPA/SCID mice were killed 6 weeks after transplantation. Blood samples were collected, and livers were removed.…”

Section: Methodsmentioning

confidence: 99%

Transdifferentiation of hepatocyte‐like cells from the human hepatoma HepaRG cell line through bipotent progenitor†

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Ces souris, constituées à la fois d'hépatocytes humains et de cellules immunitaires humaines, illustrent le potentiel de ce modèle pour étudier l'immunopathogenèse induite par l'infection par les virus hépatotropes. Ce modèle sera également utile pour l'étude de l'étape intrahépatique obligatoire du développement de Plasmodium falciparum, le parasite responsable de la malaria [35].…”

Section: Virus De La Dengueunclassified

Les souris ne sont pas des hommes et pourtant…

et al. 2012

View full text Add to dashboard Cite

“…Subsequently, human hepatocytes expressing murine CD47 transplanted in BALB-DRAG/gc-uPA mice showed a better engraftment compared to nontransduced hepatocytes [32]. These results possibly explain the better engraftment of human hepatocytes in murine models when innate immune cells such as macrophages are depleted using clodronate [33]. This is also the case for the human immune system, as demonstrated by a more stable and long-term engraftment (6e7 months) of human hepatocytes in a murine model comprising stably co-engrafted human hemato-lymphoid system [34].…”

Section: Phagocytic Cells and Ligand Recognitionmentioning

confidence: 93%

Current status of hepatocyte xenotransplantation

Meier

Navarro-Alvarez

Morel

et al. 2015

International Journal of Surgery

View full text Add to dashboard Cite

The treatment of acute liver failure, a condition with high mortality, comprises optimal clinical care, and in severe cases liver transplantation. However, there are limitations in availability of organ donors. Hepatocyte transplantation is a promising alternative that could fill the medical need, in particular as the bridge to liver transplantation. Encapsulated porcine hepatocytes represent an unlimited source that could function as a bioreactor requiring minimal immunosuppression. Besides patients with acute liver failure, patients with alcoholic hepatitis who are unresponsive to a short course of corticosteroids are a target for hepatocyte transplantation. In this review we present an overview of the innate immune barriers in hepatocyte xenotransplantation, including the role of complement and natural antibodies; the role of phagocytic cells and ligands like CD47 in the regulation of phagocytic cells; and the role of Natural Killer cells. We present also some illustrations of physiological species incompatibilities in hepatocyte xenotransplantation, such as incompatibilities in the coagulation system. An overview of the methodology for cell microencapsulation is presented, followed by proof-of-concept studies in rodent and nonhuman primate models of fulminant liver failure: these studies document the efficacy of microencapsulated porcine hepatocytes which warrants progress towards clinical application. Lastly, we present an outline of a provisional clinical trial, that upon completion of preclinical work could start within the upcoming 2-3 years

show abstract

Liver‐Stage Development ofPlasmodium falciparum,in a Humanized Mouse Model

Cited by 102 publications

References 62 publications

Transdifferentiation of hepatocyte‐like cells from the human hepatoma HepaRG cell line through bipotent progenitor†

Transdifferentiation of hepatocyte‐like cells from the human hepatoma HepaRG cell line through bipotent progenitor†

Les souris ne sont pas des hommes et pourtant…

Current status of hepatocyte xenotransplantation

Contact Info

Product

Resources

About