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“细胞活动生命活力”——中国细胞生物学学会全体会员代...

作者： kirk wangensteen Department of Genetics Cell Biology and Development

BACKGROUND & AIMS:Hepatocyte-like cells can be derived from pluripotent stem cells such as embryonic stem(ES) cells,but ES cell-derived hepatic cells with extensive capacity to repopulate liver have not been identified. We aimed to identify and purify ES cell-derived hepatoblast-like progenitor cells and to explore their capacity for liver repopulation in mice after in vitro ***:Unmanipulated mouse ES cells were cultured under defined conditions and allowed to undergo stepwise hepatic *** derived hepatic cells were examined by morphologic,fluorescence-activated cell sorting,gene expression,and clonal expansion *** capacities of ES cell-derived hepatic progenitor cells to repopulate liver were investigated in mice that were deficient in fumarylacetoacetate hydrolase(Fah)(a model of liver injury).RESULTS:Mouse ES cells were induced to differentiate into a population that contained hepatic progenitor cells;this population included cells that expressed epithelial cell adhesion molecule(EpCAM) but did not express *** hepatic progenitors that arose from single c-KitEpCAM cells could undergo long-term expansion and maintain hepatoblast-like *** c-KitEpCAM cells and clonally expanded hepatic progenitor cells repopulated the livers of Fah-deficient mice without inducing ***:ES cell-derived c-KitEpCAM cells contain a population of hepatoblast-like progenitor cells that can repopulate livers of mice.

关键词： Hepatic Differentiation Bipotency Cell Transplantation Liver Injury

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Liver Xeno-Repopulation with Human Hepatocytes in Fah-/-Rag2-/- Mice after Pharmacological Immunosuppression

Liver Xeno-Repopulation with Human Hepatocytes in Fah-/-Rag2...

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“细胞活动生命活力”——中国细胞生物学学会全体会员代...

作者： kirk J.wangensteen Stephen C.Ekker Meri Firpo Department of Genetics Cell Biology and Development Stem Cell Institute University of Minnesota55455MinnesotaUSA

Functional human hepatocytes xeno-engrafted in mouse liver can be used as a model system to study hepatitis virus infection and vaccine *** liver xeno-repopulation has been reported in two kinds of genetically modified mice that have both immune deficiency and liver injury-induced donor hepatocyte selection:the uPA/SCID mice and Fah Rag2Il2rg *** lack of hardy breeding and the overly elaborated technique in these two models may hinder the potential future application of these models to hepatitis virus infection and vaccination *** the transplantation protocol for liver xeno-repopulation from human hepatocytes will increase the model efficiency and *** this study,we successfully apply immunosuppressive drug treatments of anti-asialo GM1 and FK506 in FahRag2’ mice,resulting in significant liver xeno-repopulation from human hepatocytes and human fetal liver *** methodology decreases the risk of animal mortality during breeding and *** infected with hepatitis B virus(HBV) sera,FahRag2 mice with liver xeno-repopulation from human hepatocytes accumulate significant levels of HBV DNA and HBV *** new protocol for humanized liver could be applied in the study of human hepatitis virus infection in vivo,as well as the pharmacokinetics and efficacy of potential vaccines.

关键词： Fah-/-Rag2-/- mice humanized liver pharmacological immunosuppression human hepatocyte transplantation human fetal liver cells

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Uptake and outcomes of small intestinal and urinary tract cancer surveillance in Lynch syndrome

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World Journal of Clinical Oncology 2021年第11期12卷 1023-1036页

作者： Jeshua DeJesse Ravy K Vajravelu Christina Dudzik Gillain Constantino Jessica M Long kirk J wangensteen Kathleen D Valverde Bryson W Katona Department of Genetics University of PennsylvaniaPhiladelphiaPA 19104United States Division of Gastroenterology and Hepatology University of Pennsylvania Perelman School of MedicinePhiladelphiaPA 19104United States Division of Hematology and Oncology University of PennsylvaniaPhiladelphiaPA 19104United States

BACKGROUND Lynch syndrome(LS)is a hereditary cancer predisposition syndrome associated with increased risk of multiple *** colorectal cancer surveillance decreases mortality in LS and is recommended by guidelines,there is lack of evidence for the efficacy of surveillance for extra-colonic cancers associated with LS,including small intestinal cancer(SIC)and urinary tract cancer(UTC).Given the limited evidence,guidelines do not consistently recommend surveillance for SIC and UTC,and it remains unclear how often individuals will choose to undergo and follow through with extra-colonic surveillance *** To study factors associated with SIC and UTC surveillance uptake and outcomes in *** This is an IRB-approved retrospective analysis of individuals with LS seen at a tertiary care referral *** individuals had a pathogenic or likely pathogenic variant in MLH1,MSH2,MSH6,PMS2,or EPCAM,or were a confirmed obligate carrier,and had at least one documented visit to our *** regarding SIC and UTC surveillance was captured for each individual,and detailed personal and family history was obtained for individuals who had an initial LS management visit in our center’s dedicated high-risk LS clinic between January 1,2017 and October 29,*** these initial management visits,all patients had in-depth discussions of SIC and UTC surveillance with 1 of 3 providers experienced in LS management to promote informed decision-making about whether to pursue SIC and/or UTC *** analysis using Pearson’s chi-squared test and Wilcoxon rank-sum test was completed to understand the factors associated with pursuit and completion of SIC and UTC surveillance,and a P value below 0.05 was deemed statistically *** Of 317 individuals with LS,86(27%)underwent a total of 105 SIC surveillance examinations,with 5 leading to additional work-up and no SICs ***,99(31%)patients underwent a total of 3

关键词： Lynch syndrome Urinary tract cancer Intestinal neoplasms Early diagnosis of cancer Patient preference Gastrointestinal surgical procedure

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