Transdifferentiation of human peripheral blood CD34+-enriched cell population into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo.
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.


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.
Department of Cardiology, The University of Texas-M.D. Anderson Cancer Center, Houston, Tex, USA. etyeh@mdanderson.org
Edward T H
ET
Yeh
Sui
S
Zhang
Henry D
HD
Wu
Martin
M
Körbling
James T
JT
Willerson
Zeev
Z
Estrov
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis*; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005434:Flow Cytometry; D006085:Graft Survival; D006680:HLA Antigens / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D018952:Antigens, CD34; D000943:Antigens, Differentiation; D006680:HLA Antigens