Human CardioChimeras: Creation of a Novel ‘Next Generation’ Cardiac Cell

Abstract

AbstractBackgroundCardioChimeras (CCs) produced by fusion of murine c-kit+ cardiac interstitial cells (cCIC) with mesenchymal stem cells (MSCs) promote superior structural and functional recovery in a mouse model of myocardial infarction (MI) compared to either precursor cell alone or in combination. Creation of human CardioChimeras (hCC) represents the next step in translational development of this novel cell type, but new challenges arise when working with cCICs 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 ResultsCell fusion was induced by incubating human cCICs and MSCs 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.ConclusionsThe 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.Clinical Perspective“Next generation” cell therapeutics will build upon initial findings that demonstrate enhanced reparative action of combining distinct cell types for treatment of cardiomyopathic injury.Differential biological properties of various cell types are challenging for optimization of delivery, engraftment, persistence, and synergistic action when used in combination.Creation of a novel hybrid cell called a CardioChimera overcomes limitations inherent to use of multiple cell types.CardioChimeras exhibit unique properties relative to either parental cell anticipated to be advantageous in cellular therapeutic applications.CardioChimeras have now been created and characterized using cells derived from human heart tissue, advancing initial proof of concept previously demonstrated with mice.CardioChimeras represent an engineered solution that can be implemented as a path forward for improving the outcome of myocardial cell therapy.