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J Am Heart Assoc. 2020 Jan 7;9(1):e013452. doi: 10.1161/JAHA.119.013452. Epub 2020 Jan 4.

Human CardioChimeras: Creation of a Novel "Next-Generation" Cardiac Cell.

Author information

1
Department of Biology and Integrated Regenerative Research Institute San Diego State University San Diego CA.
2
Department of Mathematics & Statistics San Diego State University San Diego CA.

Abstract

Background CardioChimeras produced by fusion of murine c-kit+ cardiac interstitial cells with mesenchymal stem cells promote superior structural and functional recovery in a mouse model of myocardial infarction compared with either precursor cell alone or in combination. Creation of human CardioChimeras (hCCs) represents the next step in translational development of this novel cell type, but new challenges arise when working with c-kit+ cardiac interstitial cells isolated and expanded from human heart tissue samples. The objective of the study was to establish a reliable cell fusion protocol for consistent optimized creation of hCCs and characterize fundamental hCC properties. Methods and Results Cell fusion was induced by incubating human c-kit+ cardiac interstitial cells and mesenchymal stem cells at a 2:1 ratio with inactivated Sendai virus. Hybrid cells were sorted into 96-well microplates for clonal expansion to derive unique cloned hCCs, which were then characterized for various cellular and molecular properties. hCCs exhibited enhanced survival relative to the parent cells and promoted cardiomyocyte survival in response to serum deprivation in vitro. Conclusions The generation of hCC is demonstrated and validated in this study, representing the next step toward implementation of a novel cell product for therapeutic development. Feasibility of creating human hybrid cells prompts consideration of multiple possibilities to create novel chimeric cells derived from cells with desirable traits to promote healing in pathologically damaged myocardium.

KEYWORDS:

cardiac; cardiac interstitial cells; cell fusion; human; mesenchymal stromal cells

PMID:
31902324
DOI:
10.1161/JAHA.119.013452
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