北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 基础医学院  > 心血管所  > 期刊论文
学科主题: 基础医学
题名:
Microfluidic Single-Cell Analysis Shows That Porcine Induced Pluripotent Stem Cell-Derived Endothelial Cells Improve Myocardial Function by Paracrine Activation
作者: Gu, Mingxia1,3; Nguyen, Patricia K.1; Lee, Andrew S.1,2; Xu, Dan1,2; Hu, Shijun1,2; Plews, Jordan R.1,2; Han, Leng1,2; Huber, Bruno C.1,2; Lee, Won Hee1,2; Gong, Yongquan1,2,4; de Almeida, Patricia E.1,2; Lyons, Jennifer1; Ikeno, Fumi1; Pacharinsak, Cholawat5; Connolly, Andrew J.6; Gambhir, Sanjiv S.2; Robbins, Robert C.4; Longaker, Michael T.7; Wu, Joseph C.1,2,8
关键词: induced pluripotent stem cells ; large-animal models ; paracrine activation ; myocardial infarction ; molecular imaging ; ischemic heart disease ; vascular biology
刊名: CIRCULATION RESEARCH
发表日期: 2012-09-14
DOI: 10.1161/CIRCRESAHA.112.269001
卷: 111, 期:7, 页:882-893
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease
研究领域[WOS]: Cardiovascular System & Cardiology ; Hematology
关键词[WOS]: CARDIAC-FUNCTION ; GENE-EXPRESSION ; SOMATIC-CELLS ; CLINICAL TRANSLATION ; INFARCTION MODEL ; ISCHEMIC-HEART ; GENERATION ; THERAPY ; DIFFERENTIATION ; DERIVATION
英文摘要:

Rationale: Induced pluripotent stem cells (iPSCs) hold great promise for the development of patient-specific therapies for cardiovascular disease. However, clinical translation will require preclinical optimization and validation of large-animal iPSC models.

Objective: To successfully derive endothelial cells from porcine iPSCs and demonstrate their potential utility for the treatment of myocardial ischemia.

Methods and Results: Porcine adipose stromal cells were reprogrammed to generate porcine iPSCs (piPSCs). Immunohistochemistry, quantitative PCR, microarray hybridization, and angiogenic assays confirmed that piPSC-derived endothelial cells (piPSC-ECs) shared similar morphological and functional properties as endothelial cells isolated from the autologous pig aorta. To demonstrate their therapeutic potential, piPSC-ECs were transplanted into mice with myocardial infarction. Compared with control, animals transplanted with piPSC-ECs showed significant functional improvement measured by echocardiography (fractional shortening at week 4: 27.2 +/- 1.3% versus 22.3 +/- 1.1%; P<0.001) and MRI (ejection fraction at week 4: 45.8 +/- 1.3% versus 42.3 +/- 0.9%; P<0.05). Quantitative protein assays and microfluidic single-cell PCR profiling showed that piPSC-ECs released proangiogenic and antiapoptotic factors in the ischemic microenvironment, which promoted neovascularization and cardiomyocyte survival, respectively. Release of paracrine factors varied significantly among subpopulations of transplanted cells, suggesting that transplantation of specific cell populations may result in greater functional recovery.

Conclusions: In summary, this is the first study to successfully differentiate piPSCs-ECs from piPSCs and demonstrate that transplantation of piPSC-ECs improved cardiac function after myocardial infarction via paracrine activation. Further development of these large animal iPSC models will yield significant insights into their therapeutic potential and accelerate the clinical translation of autologous iPSC-based therapy. (Circ Res. 2012;111:882-893.)

语种: 英语
所属项目编号: DP2 OD004437 ; NIH RC1 HL099117 ; NIH R01 EB009689 ; NIH R33 HL0890267 ; NIH RC1 HL100490 ; U01 HL099776
项目资助者: National Institutes of Health ; Fondation Leducq ; American College of Cardiology Foundation GE Healthcare Career Development Award
WOS记录号: WOS:000308868800015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58664
Appears in Collections:基础医学院_心血管所_期刊论文

Files in This Item:
File Name/ File Size Content Type Version Access License
882.full.pdf(30953KB)期刊论文作者接受稿限制开放 联系获取全文

作者单位: 1.Stanford Univ, Dept Med, Div Cardiol, Sch Med, Stanford, CA 94305 USA
2.Stanford Univ, Mol Imaging Program, Dept Radiol, Stanford, CA 94305 USA
3.Peking Univ, Dept Physiol & Pathophysiol, Key Lab Mol Cardiovasc Sci, Educ Minist,Hlth Sci Ctr, Beijing 100871, Peoples R China
4.Stanford Univ, Dept Cardiothorac Surg, Stanford, CA 94305 USA
5.Stanford Univ, Dept Comparat Med, Stanford, CA 94305 USA
6.Stanford Univ, Dept Pathol, Stanford, CA 94305 USA
7.Stanford Univ, Dept Plast Surg, Stanford, CA 94305 USA
8.Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

Recommended Citation:
Gu, Mingxia,Nguyen, Patricia K.,Lee, Andrew S.,et al. Microfluidic Single-Cell Analysis Shows That Porcine Induced Pluripotent Stem Cell-Derived Endothelial Cells Improve Myocardial Function by Paracrine Activation[J]. CIRCULATION RESEARCH,2012,111(7):882-893.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Gu, Mingxia]'s Articles
[Nguyen, Patricia K.]'s Articles
[Lee, Andrew S.]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Gu, Mingxia]‘s Articles
[Nguyen, Patricia K.]‘s Articles
[Lee, Andrew S.]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace