机构：[1]Department of Internal Medicine, University of California Davis Medical Center , Sacramento, California.[2]Institute for Regenerative Cures, University of California Davis Medical Center , Sacramento, California.[3]Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences , Korea Cancer Center Hospital, Seoul, Korea.[4]College of Animal Science and Technology, Sichuan Agricultural University , Ya'an, China .[5]Department of Internal Medicine, Yeungnam University College of Medicine , Daegu, Korea.[6]School of Biotechnology, Southern Medical University , Guangzhou, China .[7]Department of Pathology and Laboratory Medicine, University of California Davis Medical Center , Sacramento, California.[8]Department of Dermatology, University of California Davis Medical Center , Sacramento, California.[9]Department of Pathology and of Medicine, Beth Israel Medical Center , Albert Einstein College of Medicine, New York, New York.[10]Department of Animal Science, University of California at Davis , Davis, California.
A large number of cancer stem cells (CSCs) have been isolated and identified; however, none has been cultured in an unlimited manner in vitro without losing tumorigenicity and multipotency. In this study, we successfully clonogenically cultured a newly identified CD34+ liver CSC (LCSC) on feeder cells up to 22 passages (to date) without losing CSC property. Cloned CD34+ LCSC formed a round packed morphology and it could also be cryopreserved and recultured. Stem cell markers, CD34, CD117, and SOX2; normal liver stem cell markers, alpha fetoprotein, CK19, CK18, and OV6; putative CSC markers, CD44, CD133, EpCAM, and CD90; as well as CD31 were expressed in cloned CD34+ LCSC. SOX2 was the major factor in maintaining this LCSC before colonization, and interestingly, OCT4, SOX2, NAONG, Klf4, c-Myc, and Lin28 were upregulated in association with symmetric self-renewal for colony growth of CD34+ LCSC on feeder cells. Gene expression patterns of in vitro differentiation were consistent with our in vivo finding; furthermore, the tumorigenicity of cloned CD34+ LCSC was not different from uncloned CD34+ LCSC sorted from parental PLC. These results show that our cloned CD34+ LCSC maintained CSC property, including self-renewal, bipotency, and tumorigenicity after long-term culture, demonstrating that this LCSC can be cultured in an unlimited manner in vitro. Thus, establishing pure population of CSCs isolated from the patients will provide an opportunity to explore the mechanisms of tumorigenesis and cancer development, and to identify unique biomarkers presenting potential indicators of drug efficacy against CSCs for establishment of a novel strategy for cancer therapy.
基金：
This work was supported by the NIH grant DK075415 (to
M.A.Z.) and the GlaxoSmithKline Research Fund of the
Korean Association for the Study of the Liver (to S.C.P.,
and J.R.E.).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2015]版：
大类|2 区医学
小类|2 区医学：研究与实验2 区移植3 区细胞与组织工程3 区血液学
最新[2023]版：
大类|3 区医学
小类|3 区移植4 区细胞与组织工程4 区血液学4 区医学：研究与实验
第一作者：
第一作者机构：[1]Department of Internal Medicine, University of California Davis Medical Center , Sacramento, California.[2]Institute for Regenerative Cures, University of California Davis Medical Center , Sacramento, California.[3]Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences , Korea Cancer Center Hospital, Seoul, Korea.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Internal Medicine, University of California Davis Medical Center , Sacramento, California.[2]Institute for Regenerative Cures, University of California Davis Medical Center , Sacramento, California.[8]Department of Dermatology, University of California Davis Medical Center , Sacramento, California.[10]Department of Animal Science, University of California at Davis , Davis, California.[*1]Department of Internal Medicine University of California Davis Medical Center Sacramento, CA 95817[*2]Department of Animal Science University of California at Davis Davis, CA 95616
推荐引用方式(GB/T 7714)：
Park Su Cheol,Zeng Changjun,Tschudy-Seney Benjamin,et al.Clonogenically Culturing and Expanding CD34+ Liver Cancer Stem Cells in Vitro.[J].Stem cells and development.2015,24(13):1506-14.doi:10.1089/scd.2015.0022.
APA：
Park Su Cheol,Zeng Changjun,Tschudy-Seney Benjamin,Nguyen Ngoc Tue,Eun Jong Ryeol...&Duan Yuyou.(2015).Clonogenically Culturing and Expanding CD34+ Liver Cancer Stem Cells in Vitro..Stem cells and development,24,(13)
MLA：
Park Su Cheol,et al."Clonogenically Culturing and Expanding CD34+ Liver Cancer Stem Cells in Vitro.".Stem cells and development 24..13(2015):1506-14
