Angiogenic Stem Cell Delivery Platform to Augment Post-infarction Neovasculature and Reverse Ventricular Remodeling

Overview

Journal Sci Rep

Specialty Science

Date 2022 Oct 20

PMID 36266453

Authors

Hye Sook Shin

Akshara Thakore

Yuko Tada

Albert J Pedroza

Gentaro Ikeda

Ian Y Chen

Doreen Chan

Kevin J Jaatinen

Shin Yajima

Eric M Pfrender

Masashi Kawamura

Phillip C Yang

Joseph C Wu

Eric A Appel

Michael P Fischbein

YJoseph Woo

Yasuhiro Shudo

Affiliations

Soon will be listed here.

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.

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