Human CD34+ cells in experimental myocardial infarction: long-term survival, sustained functional improvement, and mechanism of action.
BACKGROUND
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.


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<0.05). Furthermore, treatment with anti-alpha4beta1 showed that generation of human-derived cardiomyocytes was inhibited, whereas anti-vascular endothelial growth factor (VEGF) treatment blocked the production of human-derived endothelial cells. However, the improvement in cardiac function was abolished only in the anti-VEGF, but not anti-alpha4beta1, treated group.


CONCLUSIONS
Angiogenesis and/or paracrine effect, but not myogenesis, is responsible for functional improvement following CD34(+) cells therapy.
Wang
Jingxiong
J
University of Texas-MD Anderson Cancer Center, 1400 Pressler Blvd, Box 1451, Houston, TX 77030, USA.
Zhang
Sui
S
Rabinovich
Brian
B
Bidaut
Luc
L
Soghomonyan
Suren
S
Alauddin
Mian M
MM
Bankson
James A
JA
Shpall
Elizabeth
E
Willerson
James T
JT
Gelovani
Juri G
JG
Yeh
Edward T H
ET
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology; D049268:Positron-Emission Tomography; D013318:Stroke Volume / Q000502:physiology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D014057:Tomography, X-Ray Computed
D018952:Antigens, CD34
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