Abstract
Since both myocardium and vasculature in the heart are excessively damaged following myocardial infarction (MI), therapeutic strategies for treating MI hearts should concurrently target both so as to achieve true cardiac repair. Here we demonstrate a concomitant method that exploits the advantages of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and human mesenchymal stem cell-loaded patch (hMSC-PA) to amplify cardiac repair in a rat MI model. Epicardially implanted hMSC-PA provide a complimentary microenvironment which enhances vascular regeneration through prolonged secretion of paracrine factors, but more importantly it significantly improves the retention and engraftment of intramyocardially injected hiPSC-CMs which ultimately restore the cardiac function. Notably, the majority of injected hiPSC-CMs display adult CMs like morphology suggesting that the secretomic milieu of hMSC-PA constitutes pleiotropic effects in vivo. We provide compelling evidence that this dual approach can be a promising means to enhance cardiac repair on MI hearts.
Highlights
Since both myocardium and vasculature in the heart are excessively damaged following myocardial infarction (MI), therapeutic strategies for treating MI hearts should concurrently target both so as to achieve true cardiac repair
Human mesenchymal stem cells have long been considered a promising candidate for cell-based therapy owed to their beneficial paracrine factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and hepatocyte growth factor (HGF) that promote angiogenesis, neovascularization, and cell survival3. human mesenchymal stem cells (hMSCs) are known to secrete potent anti-fibrotic factors including matrix metalloproteinases 2, 9, and 14, which inhibit the proliferation of cardiac fibroblasts thereby attenuating fibrosis[4]
To select the best candidate of hMSCs in terms of secretion of paracrine factors, we examined distinct types of hMSCs isolated from different sources such as human turbinate, human adipose tissue, and human bone marrow and compared the concentration of VEGF secreted to their conditioned medium
Summary
Since both myocardium and vasculature in the heart are excessively damaged following myocardial infarction (MI), therapeutic strategies for treating MI hearts should concurrently target both so as to achieve true cardiac repair. Do the implanted hMSC-PA significantly increase the retention of intramyocardially injected hiPSC-CMs and preserve injured host CMs via paracrine release of cytokines and growth factors, resulting in functional improvement.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
