Induced pluripotent stem cell (iPSC)-derived Flk-1 progenitor cells engraft, differentiate, and improve heart function in a mouse model of acute myocardial infarction

被引：116

作者：

Mauritz, Christina ^{[1
]}

Martens, Andreas ^{[1
]}

Rojas, Sebastian V. ^{[1
]}

Schnick, Tilman ^{[1
]}

Rathert, Christian ^{[1
]}

Schecker, Natalie ^{[1
]}

Menke, Sandra ^{[1
]}

Glage, Silke ^{[2
]}

Zweigerdt, Robert ^{[1
]}

Haverich, Axel ^{[1
]}

Martin, Ulrich ^{[1
]}

Kutschka, Ingo ^{[1
]}

机构：

[1] Hannover Med Sch, Dept Cardiothorac Transplantat & Vasc Surg, REBIRTH Cluster Excellence, Leibniz Res Labs Biotechnol & Artificial Organs L, D-30625 Hannover, Germany

[2] Hannover Med Sch, Inst Lab Anim Sci, D-30625 Hannover, Germany

来源：

EUROPEAN HEART JOURNAL | 2011年 / 32卷 / 21期

关键词：

Cardiovascular progenitor cells; Induced pluripotent stem cells; Myocardial infarction; Myocardial regeneration; CARDIAC PROGENITORS; SMOOTH-MUSCLE; MULTIPOTENT; FIBROBLASTS; GENERATION; IDENTIFICATION; CARDIOMYOCYTE; EXPRESSION; INDUCTION; LINEAGES;

D O I：

10.1093/eurheartj/ehr166

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims Induced pluripotent stem cell (iPSC)-derived cardiovascular progenitor cells represent a suitable autologous cell source for myocardial regeneration as they have the capability to form myocardial cells and to contribute to revascularization. As a first proof of concept we evaluated the potential of a murine iPSC-derived cardiovascular progenitor population, which expresses the surface marker foetal liver kinase-1 (Flk-1), to restore myocardial tissue and improve cardiac function after acute myocardial infarction (MI) in mice. Methods and results iPSC-derived Flk-1(pos) vs. Flk-1(neg) cells were selected by fluorescence activated cell sorting (FACS) and injected into the ischaemic myocardium of left anterior descending coronary artery (LAD)-ligated mice. Addressing safety aspects we used an octamer binding factor 4 (Oct4)-enhanced green fluorescent protein (eGFP) expressing iPSC clone from the transgenic Oct4-eGFP reporter mouse strain OG2 to enable FACS-based depletion of undifferentiated cells prior to transplantation. Infarcted animals were treated with placebo (phosphate-buffered saline, n = 13), Flk-1(neg) cells (n = 14), or Flk-1(pos) cells (n = 11; 5 x 10(5) cells each). Heart function was evaluated by magnetic resonance imaging and conductance catheter analysis 2 weeks postoperatively. Cardiovascular in vitro and in vivo differentiations were investigated by immunofluorescence staining. Treatment with Flk-1(pos) and Flk-1(neg) cells resulted in a favourable myocardial remodelling and improved left ventricular function. Engraftment and functional benefits were superior after transplantation of Flk-1pos compared with Flk-1(neg) cells. Furthermore, Flk-1(pos) grafts contained considerably more vascular structures in relation to Flk-1(neg) grafts. Conclusion iPSC-derived Flk-1(pos) progenitor cells differentiate into cardiovascular lineages in vitro and in vivo and improve cardiac function after acute MI.

引用

页码：2634 / 2641

页数：8

共 23 条

[1] Flk1+cardiac stem/progenitor cells derived from embryonic stem cells improve cardiac function in a dilated cardiomyopathy mouse model [J].