Cardiac Stem Cell Hybrids Enhance Myocardial Repair

Abstract

Rationale Dual cell transplantation of cardiac progenitor cells (CPCs) and mesenchymal stem cells (MSCs) after infarction improves myocardial repair and performance in large animal models relative to delivery of either cell population. Objective To demonstrate that CardioChimeras (CCs) formed by fusion between CPCs and MSCs have enhanced reparative potential in a mouse model of myocardial infarction relative to individual stem cells or combined cell delivery. Methods and Results Two distinct and clonally derived CCs, CC1 and CC2 were utilized for this study. CCs improved left ventricular anterior wall thickness (AWT) at 4 weeks post injury, but only CC1 treatment preserved AWT at 18 weeks. Ejection fraction was enhanced at 6 weeks in CCs, and functional improvements were maintained in CCs and CPC + MSC groups at 18 weeks. Infarct size was decreased in CCs, whereas CPC + MSC and CPC parent groups remained unchanged at 12 weeks. CCs exhibited increased persistence, engraftment, and expression of early commitment markers within the border zone relative to combinatorial and individual cell population-injected groups. CCs increased capillary density and preserved cardiomyocyte size in the infarcted regions suggesting CCs role in protective paracrine secretion. Conclusions CCs merge the application of distinct cells into a single entity for cellular therapeutic intervention in the progression of heart failure. CCs are a novel cell therapy that improves upon combinatorial cell approaches to support myocardial regeneration.

Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

“…In spite of the inherent disadvantages of genomic instability, cell senescence and the virus-mediated cell fusion, which hamper ready clinical translation, it was found that chimera therapy better improved cell engraftment, reduced scar size and increased angiogenesis. Besides, it surpassed single and dual cell therapies in terms of LV function amelioration [10]. Therefore, this finding encourages further investigation in the field of cell chimeras, mainly with regard to therapy safety, which is now the main concern before getting into pre-clinical trials.…”

“…In this regard, stem cell-based therapies have been a hot topic of research lately. The ultimate goal of stem cell therapy is to replace nonviable myocardium by functional building blocks both at the cellular and tissue levels [4,9,10] and/or to encourage endogenous cardiac repair mechanisms [10,11]. It is our goal to review current investigations on cell therapy for heart diseases as well as to address their limitations and potentials.…”

Cardiac Regenerative Medicine: The Potential of a New Generation of Stem Cells

“…CCs were formed by ex vivo viral cell fusion between MSCs and CPCs and were allowed to undergo clonal expansion [51]. Two different clones with enhanced proliferation and survival properties (CC1 and CC2) were chosen for further comparison with individual cell and combinatorial therapies in a mouse MI model.…”

Circulation Research “In This Issue” Anthology

“…The authors suggest future clinical trials are needed to build upon these preliminary results. CardioChimeras Enhance Myocardial Repair (p 695) 50 Quijada et al create two-in-one hybrid cells for repairing heart injuries.…”