Functional and Transcriptional Characterization of Human Embryonic Stem Cell-Derived Endothelial Cells for Treatment of Myocardial Infarction

被引：103

作者：

Li, Zongjin ^{[1
,2
,8
]}

Wilson, Kitchener D. ^{[1
,2
,3
]}

Smith, Bryan ^{[1
,2
]}

Kraft, Daniel L. ^{[4
]}

Jia, Fangjun ^{[1
,2
]}

Huang, Mei ^{[1
,2
]}

Xie, Xiaoyan ^{[1
,2
]}

Robbins, Robert C. ^{[5
]}

Gambhir, Sanjiv S. ^{[1
,2
]}

Weissman, Irving L. ^{[4
,6
]}

Wu, Joseph C. ^{[1
,2
,6
,7
]}

机构：

[1] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, MIPS, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Dept Bioengn, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA

[5] Stanford Univ, Sch Med, Dept Cardiothorac Surg, Stanford, CA 94305 USA

[6] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[7] Stanford Univ, Sch Med, Div Cardiol, Dept Med, Stanford, CA 94305 USA

[8] Nankai Univ, Sch Med, Tianjin 300071, Peoples R China

来源：

PLOS ONE | 2009年 / 4卷 / 12期

关键词：

PROGENITOR CELLS; EXTRACELLULAR-MATRIX; PERIPHERAL-BLOOD; CORD BLOOD; CARDIOMYOCYTES; MORPHOGENESIS; NEOVASCULARIZATION; TRANSPLANTATION; ISCHEMIA; SURVIVAL;

D O I：

10.1371/journal.pone.0008443

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: Differentiation of human embryonic stem cells into endothelial cells (hESC-ECs) has the potential to provide an unlimited source of cells for novel transplantation therapies of ischemic diseases by supporting angiogenesis and vasculogenesis. However, the endothelial differentiation efficiency of the conventional embryoid body (EB) method is low while the 2-dimensional method of co-culturing with mouse embryonic fibroblasts (MEFs) require animal product, both of which can limit the future clinical application of hESC-ECs. Moreover, to fully understand the beneficial effects of stem cell therapy, investigators must be able to track the functional biology and physiology of transplanted cells in living subjects over time. Methodology: In this study, we developed an extracellular matrix (ECM) culture system for increasing endothelial differentiation and free from contaminating animal cells. We investigated the transcriptional changes that occur during endothelial differentiation of hESCs using whole genome microarray, and compared to human umbilical vein endothelial cells (HUVECs). We also showed functional vascular formation by hESC-ECs in a mouse dorsal window model. Moreover, our study is the first so far to transplant hESC-ECs in a myocardial infarction model and monitor cell fate using molecular imaging methods. Conclusion: Taken together, we report a more efficient method for derivation of hESC-ECs that express appropriate patterns of endothelial genes, form functional vessels in vivo, and improve cardiac function. These studies suggest that hESC-ECs may provide a novel therapy for ischemic heart disease in the future.

引用

页数：13

共 42 条

[1] Biomechanical forces promote embryonic haematopoiesis [J].