Angiogenic stem cell delivery platform to augment post-infarction neovasculature and reverse ventricular remodeling

• Published in: Scientific reports Vol. 12; no. 1; pp. 17605 - 21
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.10.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308; 692/308/575; Angiogenesis; Animals; Biocompatibility; Biocompatible Materials; Biodegradable materials; Biomaterials; Biomimetics; Bone marrow; Cardiac function; Cardiomyopathy; Cell interactions; Cells, Cultured; CXCL12 protein; Heart attacks; Humanities and Social Sciences; Humans; Ischemia; Localization; Materials science; Medicine; Microenvironments; Morphology; multidisciplinary; Myocardial infarction; Myocardial Infarction - metabolism; Myocardium; Neovascularization, Physiologic; Progenitor cells; Rats; Scanning electron microscopy; Science; Science (multidisciplinary); Smooth muscle; Stem Cell Transplantation; Stem cells; Stem Cells - metabolism; Ventricle; Ventricular Remodeling
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-21510-y

Many 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.