Enhancing myocardial repair with CardioClusters

Megan M. Monsanto, Bingyan J. Wang, Zach R. Ehrenberg, Oscar Echeagaray, Kevin S. White, Roberto Alvarez, Kristina Fisher, Sharon Sengphanith, Alvin Muliono, Natalie A. Gude and Mark A. Sussman ()
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Megan M. Monsanto: San Diego State University
Bingyan J. Wang: San Diego State University
Zach R. Ehrenberg: San Diego State University
Oscar Echeagaray: San Diego State University
Kevin S. White: San Diego State University
Roberto Alvarez: San Diego State University
Kristina Fisher: San Diego State University
Sharon Sengphanith: San Diego State University
Alvin Muliono: San Diego State University
Natalie A. Gude: San Diego State University
Mark A. Sussman: San Diego State University

Nature Communications, 2020, vol. 11, issue 1, 1-20

Abstract: Abstract Cellular therapy to treat heart failure is an ongoing focus of intense research, but progress toward structural and functional recovery remains modest. Engineered augmentation of established cellular effectors overcomes impediments to enhance reparative activity. Such ‘next generation’ implementation includes delivery of combinatorial cell populations exerting synergistic effects. Concurrent isolation and expansion of three distinct cardiac-derived interstitial cell types from human heart tissue, previously reported by our group, prompted design of a 3D structure that maximizes cellular interaction, allows for defined cell ratios, controls size, enables injectability, and minimizes cell loss. Herein, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and c-Kit+ cardiac interstitial cells (cCICs) when cultured together spontaneously form scaffold-free 3D microenvironments termed CardioClusters. scRNA-Seq profiling reveals CardioCluster expression of stem cell-relevant factors, adhesion/extracellular-matrix molecules, and cytokines, while maintaining a more native transcriptome similar to endogenous cardiac cells. CardioCluster intramyocardial delivery improves cell retention and capillary density with preservation of cardiomyocyte size and long-term cardiac function in a murine infarction model followed 20 weeks. CardioCluster utilization in this preclinical setting establish fundamental insights, laying the framework for optimization in cell-based therapeutics intended to mitigate cardiomyopathic damage.

Date: 2020
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DOI: 10.1038/s41467-020-17742-z

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