Treatment with hESC-Derived Myocardial Precursors Improves Cardiac Function after a Myocardial Infarction

• Published in: PloS one 2015-07, Vol.10 (7), p.e0131123
• Main Authors: Ye, Jianqin, Gaur, Meenakshi, Zhang, Yan, Sievers, Richard E, Woods, Brandon J, Aurigui, Julian, Bernstein, Harold S, Yeghiazarians, Yerem
• Format: Article
• Language: English
• Subjects: Amino acids; Angiogenesis; Animals; Apoptosis; Apoptosis - physiology; Bone marrow; Cardiomyocytes; Cell fate; Cell size; Cell- and Tissue-Based Therapy - methods; Cells, Cultured; Cytokines; Echocardiography; Embryo cells; Embryonic Stem Cells - transplantation; Embryos; Female; Fetuses; Fibroblasts; Fluorescence; Green fluorescent protein; Green Fluorescent Proteins - genetics; Heart; Heart - physiopathology; Heart attacks; Heart diseases; Heart failure; Heart Function Tests; Human behavior; Humans; Hypotheses; Immunodeficiency; Medical research; Medicine; Mice; Mice, SCID; Multipotent Stem Cells - transplantation; Myocardial infarction; Myocardial Infarction - therapy; Myocardium; Myocytes, Cardiac - cytology; Myosin; Neovascularization, Physiologic; Paracrine signalling; Precursors; Rodents; Skin; Stem cell transplantation; Stem cells; Teratoma; Ultrasound
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0131123

We previously reported the generation of a reporter line of human embryonic stem cells (hESCs) with enhanced green fluorescent protein (eGFP) expression driven by the α-myosin heavy chain (αMHC) promoter. The GFP+/αMHC+ cells derived from this cell line behave as multipotent, human myocardial precursors (hMPs) in vitro. In this study, we evaluated the therapeutic effects of GFP+/αMHC+ cells isolated from the reporter line in a mouse model of myocardial infarction (MI). MI was generated in immunodeficient mice. hMPs were injected into murine infarcted hearts under ultrasound guidance at 3 days post-MI. Human fetal skin fibroblasts (hFFs) were injected as control. Cardiac function was evaluated by echocardiography. Infarct size, angiogenesis, apoptosis, cell fate, and teratoma formation were analyzed by immunohistochemical staining. Compared with control, hMPs resulted in improvement of cardiac function post-MI with smaller infarct size, induced endogenous angiogenesis, and reduced apoptosis of host cardiomyocytes at the peri-infarct zone at 28 days post-MI. Intramyocardial injection of hMPs improved cardiac function post-MI. The engraftment rate of these cells in the myocardium post-MI was low, suggesting that the majority of effect occurs via paracrine mechanisms.