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学科主题基础医学
Microfluidic Single-Cell Analysis Shows That Porcine Induced Pluripotent Stem Cell-Derived Endothelial Cells Improve Myocardial Function by Paracrine Activation
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
2012-09-14
DOI10.1161/CIRCRESAHA.112.269001
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
WOS记录号WOS:000308868800015
项目编号DP2 OD004437 ; NIH RC1 HL099117 ; NIH R01 EB009689 ; NIH R33 HL0890267 ; NIH RC1 HL100490 ; U01 HL099776
资助机构National Institutes of Health ; Fondation Leducq ; American College of Cardiology Foundation GE Healthcare Career Development Award
引用统计
被引频次:49[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58664
专题北京大学基础医学院_心血管所
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
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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.
APA Gu, Mingxia.,Nguyen, Patricia K..,Lee, Andrew S..,Xu, Dan.,Hu, Shijun.,...&Wu, Joseph C..(2012).Microfluidic Single-Cell Analysis Shows That Porcine Induced Pluripotent Stem Cell-Derived Endothelial Cells Improve Myocardial Function by Paracrine Activation.CIRCULATION RESEARCH,111(7),882-893.
MLA Gu, Mingxia,et al."Microfluidic Single-Cell Analysis Shows That Porcine Induced Pluripotent Stem Cell-Derived Endothelial Cells Improve Myocardial Function by Paracrine Activation".CIRCULATION RESEARCH 111.7(2012):882-893.
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