Human CD34+ Cells in Experimental Myocardial Infarction. Long-Term Survival, Sustained Functional Improvement, and Mechanism of Action

Rationale: Human CD34 + cells have been used in clinical trials for treatment of myocardial infarction (MI). However, it is unknown how long the CD34 + cells persist in hearts, whether the improvement in cardiac function is sustained, or what are the underlying mechanisms. Objective: We sought to track the fate of injected human CD34 + cells in the hearts of severe combined immune deficiency (SCID) mice after experimental MI and to determine the mechanisms of action. Methods and Results: We used multimodality molecular imaging to track the fate of injected human CD34 + cells in the hearts of SCID mice after experimental MI, and used selective antibody blocking to determine the mechanisms of action. Bioluminescence imaging showed that injected CD34 + cells survived in the hearts for longer than 12 months. The PET signal from the injected cells was detected in the wall of the left ventricle. Cardiac MRI showed that left ventricular ejection fraction was significantly improved in the treated mice compared to the control mice for up to 52 weeks ( P Conclusions: Angiogenesis and/or paracrine effect, but not myogenesis, is responsible for functional improvement following CD34 + cells therapy.