De novo Biological Coronary Artery Bypass in a Rat Model: Case Report and the Concept of Hybrid Cardiovascular Regeneration

Abstract

Background: Peripheral blood mononuclear cell-derived progenitor cells (regeneration associated cells: RACs) have been reported to migrate to tissues with inflammation to expedite anti-inflammatory and pro-regeneration actions, but cell sources, administration, timing, dosage, and combined procedures after myocardial ischemia and/or infarction (MI) still remain to be elucidated in preclinical studies. Materials and Methods: Rats with induced MI were treated with intravenous infusion of 5-day culture-primed autologous RACs or control cell transfusion, followed by weekly echocardiography until 4 weeks after MI, at which time pressure-volume relationship (PVR) analyses and histological studies were performed. Results: While most rats treated with autologous RACs infusion after MI developed vascular regeneration from surrounding pericardial tissues and significant functional improvements, one rat developed a de novo coronary artery bypass (φ< 0.3 mm) mimicking surgical bypass grafting (CABG), echocardiography revealed recovered left ventricular (LV) motion, and PVR analyses showed restored LV function as well as histological changes suggesting revascularization and myocardial regeneration. Conclusion: Development of isolated bypass-like structure by RAC therapy after MI led us to consider further surgical as well as biological modifications to expedite biological coronary revascularization and myocardial regeneration. A combination with vascular approaches to provide arterial inflow may increase the rate of complete revascularization and regeneration of cardiomyocytes as hybrid procedure, as they complement each other, to realize cardiovascular regeneration.