Bioengineered Myocardium Derived from Induced Pluripotent Stem Cells Improves Cardiac Function and Attenuates Cardiac Remodeling Following Chronic Myocardial Infarction in Rats

Abstract

Cell-based therapies are promising strategies for myocardial repair following myocardial infarction. Induced pluripotent stem (iPS) cells have the potential to generate many cardiomyocytes, and they hold significant promise for the application of regenerative medicine to heart failure. Here, we developed cardiac tissue sheets, termed bioengineered myocardium (BM), from mouse iPS cells and measured cardiac performance following BM implantation in a rat chronic myocardial infarction model. Immunostaining analyses revealed that the ␣-actinin ؉ cell population was isolated with more than 99% purity under specific culture conditions. To evaluate the contribution of BM to the improvements in cardiac performance, we induced myocardial infarction in 30 F344/NJcl-rnu/rnu rats by left anterior descending coronary ligation. The rats were randomly divided into two groups, 2 weeks after ligation: a BM implantation group (n ‫؍‬ 15) and a sham group (n ‫؍‬ 15). Echocardiography and catheter examination showed that the BM implantation significantly improved cardiac function and attenuated cardiac remodeling compared with the sham group. Histological analyses demonstrated that the implanted BM survived at the epicardial implantation site 4 weeks after implantation. The implanted BM survived and attenuated left ventricular remodeling in the rat chronic myocardial infarction model. Thus, BM derived from iPS cells might be a promising new treatment for heart failure. STEM CELLS TRANSLATIONAL MEDICINE 2012;1:430 -437

In vitro and in vivo delivery of genes and proteins using the bacteriophage T4 DNA packaging machine

“…T4 heads delivering recombinase and targeting molecules displayed outside, and genomic DNA and siRNA genes packaged inside, could be used in cancer therapy, either to kill cancer cells by induction of apoptosis or to reverse the cancer phenotype by turning off certain oncogenes (30). T4 delivery might allow safe and efficient reprograming of pluripotent stem cells by delivering transcription factor genes and proteins such as c-Myc, kruppel-like factor 4 (Klf4), sex determining region Y box 2 (Sox2), and octamer-binding transcription factor (Oct3/4), as well as replacing the defective gene with a functional gene by in vivo delivery of a long stretch of genomic DNA (31).…”

Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured Myocardium

“…hESCs and iPSCs differentiate robustly into a highly purified population of functional cardiac myocytes in vitro 12, 13 . Functional improvement of the injured myocardium has been observed in murine, rodent, and porcine models that received either hESCs-derived cardiac myocytes (hCMs) 12, 14-20 or iPSCs-derived cardiac myocytes (iCMs) 21, 22 . Additionally, pluripotent stem cell-derived cardiac myocytes have been shown to engraft and improve heart function more effectively than non-cardiac derivatives 12, 17-19 .…”

Current status of stem cell therapy: opportunities and limitations

“…In cardiac repair, some promising results were related to the use of collagen scaffolds, reported to enhance the survival of cardiomyoblasts and improve survival of ischemic rats (Miki et al, 2012). Injection of biomimetic scaffolds at the site of myocardial infarction (eventually supplemented with bioactive molecules) is reported to decrease the amount of fibrosis and ventricular dilation and to promote angiogenesis and recruitment of native stem cells (Kutschka et al, 2006;Zamora et al, 2013).…”