Author:
Shin Hye Sook,Thakore Akshara,Tada Yuko,Pedroza Albert J.,Ikeda Gentaro,Chen Ian Y.,Chan Doreen,Jaatinen Kevin J.,Yajima Shin,Pfrender Eric M.,Kawamura Masashi,Yang Phillip C.,Wu Joseph C.,Appel Eric A.,Fischbein Michael P.,Woo YJoseph,Shudo Yasuhiro
Abstract
AbstractMany cell-based therapies are challenged by the poor localization of introduced cells and the use of biomaterial scaffolds with questionable biocompatibility or bio-functionality. Endothelial progenitor cells (EPCs), a popular cell type used in cell-based therapies due to their robust angiogenic potential, are limited in their therapeutic capacity to develop into mature vasculature. Here, we demonstrate a joint delivery of human-derived endothelial progenitor cells (EPC) and smooth muscle cells (SMC) as a scaffold-free, bi-level cell sheet platform to improve ventricular remodeling and function in an athymic rat model of myocardial infarction. The transplanted bi-level cell sheet on the ischemic heart provides a biomimetic microenvironment and improved cell–cell communication, enhancing cell engraftment and angiogenesis, thereby improving ventricular remodeling. Notably, the increased density of vessel-like structures and upregulation of biological adhesion and vasculature developmental genes, such as Cxcl12 and Notch3, particularly in the ischemic border zone myocardium, were observed following cell sheet transplantation. We provide compelling evidence that this SMC-EPC bi-level cell sheet construct can be a promising therapy to repair ischemic cardiomyopathy.
Funder
National Institutes of Health, United States
Stanford Cardiovascular Institute (CVI) and Gootter Foundation Seed Grant Awards
Publisher
Springer Science and Business Media LLC
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