Transdifferentiation of Human Peripheral Blood CD34 + -Enriched Cell Population Into Cardiomyocytes, Endothelial Cells, and Smooth Muscle Cells In Vivo

Abstract

Background— Adult human peripheral blood cells have been shown to differentiate into mature cells of nonhematopoietic tissues, such as hepatocytes and epithelial cells of the skin and gastrointestinal track. We investigated whether these cells could also transdifferentiate into human cardiomyocytes, mature endothelial cells, and smooth muscle cells in vivo. Methods and Results— Myocardial infarction was created in SCID mice by occluding the left anterior descending coronary artery, after which adult peripheral blood CD34⁺ cells were injected into the tail vein. Hearts were harvested 2 months after injection and stained for human leukocyte antigen (HLA) and markers for cardiomyocytes, endothelial cells, and smooth muscle cells. Cardiomyocytes, endothelial cells, and smooth muscle cells that bear HLA were identified in the infarct and peri-infarct regions of the mouse hearts. In a separate experiment, CD34⁺ cells were injected intraventricularly into mice without experimental myocardial infarction. HLA-positive myocytes and smooth muscle cells could only be identified in 1 of these mice killed at different time points. Conclusions— Adult peripheral blood CD34⁺ cells can transdifferentiate into cardiomyocytes, mature endothelial cells, and smooth muscle cells in vivo. However, transdifferentiation is augmented significantly by local tissue injury. The use of peripheral blood CD34⁺ cells for cell-based therapy should greatly simplify the procurement of cells for the regeneration of damaged myocardium.