Abstract

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.

Details

Title
Angiogenic stem cell delivery platform to augment post-infarction neovasculature and reverse ventricular remodeling
Author
Shin, Hye Sook 1 ; Thakore, Akshara 1 ; Tada, Yuko 2 ; Pedroza, Albert J. 1 ; Ikeda, Gentaro 2 ; Chen, Ian Y. 2 ; Chan, Doreen 3 ; Jaatinen, Kevin J. 4 ; Yajima, Shin 1 ; Pfrender, Eric M. 1 ; Kawamura, Masashi 4 ; Yang, Phillip C. 2 ; Wu, Joseph C. 2 ; Appel, Eric A. 5 ; Fischbein, Michael P. 1 ; Woo, YJoseph 1 ; Shudo, Yasuhiro 1 

 Stanford University School of Medicine, Department of Cardiothoracic Surgery, Falk Cardiovascular Research Center, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956); Stanford University School of Medicine, Stanford Cardiovascular Institute, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
 Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956); Stanford University School of Medicine, Stanford Cardiovascular Institute, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
 Stanford University, Stanford University, Department of Chemistry, Department of Materials Science & Engineering, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
 Stanford University School of Medicine, Department of Cardiothoracic Surgery, Falk Cardiovascular Research Center, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
 Stanford University, Department of Materials Science & Engineering, Department of Bioengineering, Department of Pediatric (Endocrinology), Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2726711728
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.