中文版 | English
题名

Generation of Human Liver Chimeric Mice with Hepatocytes from Familial Hypercholesterolemia Induced Pluripotent Stem Cells

作者
通讯作者Esteban, Miguel A.; Tse, Hung-Fat
发表日期
2017-03-14
DOI
发表期刊
ISSN
2213-6711
卷号8期号:3页码:605-618
摘要

Familial hypercholesterolemia (FH) causes elevation of low-density lipoprotein cholesterol (LDL-C) in blood and carries an increased risk of early-onset cardiovascular disease. A caveat for exploration of new therapies for FH is the lack of adequate experimental models. We have created a comprehensive FH stem cell model with differentiated hepatocytes (iHeps) from human induced pluripotent stem cells (iPSCs), including genetically engineered iPSCs, for testing therapies for FH. We used FH iHeps to assess the effect of simvastatin and proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies on LDL-C uptake and cholesterol lowering in vitro. In addition, we engrafted FH iHeps into the liver of Ldlr(-/-) /Rag2(-/-) /Il2rg(-/-) mice, and assessed the effect of these same medications on LDL-C clearance and endothelium-dependent vasodilation in vivo. Our iHep models recapitulate clinical observations of higher potency of PCSK9 antibodies compared with statins for reversing the consequences of FH, demonstrating the utility for preclinical testing of new therapies for FH patients.

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语种
英语
学校署名
其他
资助项目
Youth Innovation Promotion Association of the Chinese Academy of Sciences[2015294]
WOS研究方向
Cell Biology
WOS类目
Cell & Tissue Engineering ; Cell Biology
WOS记录号
WOS:000397103900011
出版者
来源库
Web of Science
引用统计
被引频次[WOS]:25
成果类型期刊论文
条目标识符http://sustech.caswiz.com/handle/2SGJ60CL/29067
专题生命科学学院_生物系
作者单位
1.Univ Hong Kong, Li Ka Shing Fac Med, Dept Med, Div Cardiol, Hong Kong, Hong Kong, Peoples R China
2.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Joint Sch Life Sci, CAS Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China
3.Guangzhou Med Univ, Guangzhou 511436, Guangdong, Peoples R China
4.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, CAS Key Lab Regenerat Biol, Lab RNA Chromatin & Human Dis, Guangzhou 510530, Guangdong, Peoples R China
5.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Stem Cells & Regenerat Med, Guangzhou 510530, Guangdong, Peoples R China
6.Chinese Univ Hong Kong, Inst Vasc Med, Li Ka Shing Inst Hlth Sci, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China
7.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, CAS Key Lab Regenerat Biol, Lab Metab & Cell Fate, Guangzhou 510530, Guangdong, Peoples R China
8.Southern Univ Sci & Technol China, Dept Biol, Shenzhen 518055, Peoples R China
9.Univ Hong Kong, Li Ka Shing Fac Med, Res Ctr Heart Brain Hormone & Hlth Ageing, Hong Kong, Hong Kong, Peoples R China
10.Univ Hong Kong, Hong Kong Guangdong Stem Cell & Regenerat Med Res, Hong Kong, Hong Kong, Peoples R China
11.Guangzhou Inst Biomed & Hlth, Hong Kong, Hong Kong, Peoples R China
12.Univ Hong Kong, Dept Med, Shenzhen Hosp, Shenzhen 518053, Peoples R China
推荐引用方式
GB/T 7714
Yang, Jiayin,Wang, Yu,Zhou, Ting,et al. Generation of Human Liver Chimeric Mice with Hepatocytes from Familial Hypercholesterolemia Induced Pluripotent Stem Cells[J]. Stem Cell Reports,2017,8(3):605-618.
APA
Yang, Jiayin.,Wang, Yu.,Zhou, Ting.,Wong, Lai-Yung.,Tian, Xiao-Yu.,...&Tse, Hung-Fat.(2017).Generation of Human Liver Chimeric Mice with Hepatocytes from Familial Hypercholesterolemia Induced Pluripotent Stem Cells.Stem Cell Reports,8(3),605-618.
MLA
Yang, Jiayin,et al."Generation of Human Liver Chimeric Mice with Hepatocytes from Familial Hypercholesterolemia Induced Pluripotent Stem Cells".Stem Cell Reports 8.3(2017):605-618.
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