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

Wang, Jingxiong and Zhang, Sui and Rabinovich, Brian and Bidaut, Luc and Soghomonyan, Suren and Alauddin, Mian M. and Bankson, James A. and Shpall, Elizabeth and Willerson, James T. and Gelovani, Juri G. and Yah, Edward T. H. (2010) Human CD34+ cells in experimental myocardial infarction: long-term survival, sustained functional improvement, and mechanism of action. Circulation Research, 106 (12). pp. 1904-1911. ISSN 0009-7330

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Abstract

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<0.05). Furthermore, treatment with anti-α4β1 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-α4β1, treated group. Conclusions: Angiogenesis and/or paracrine effect, but not myogenesis, is responsible for functional improvement following CD34 cells therapy. © 2010 American Heart Association, Inc.

Additional Information:This work was presented in part at the American Heart Association Scientific Sessions, Orlando, Fla, November 3-7, 2007, and published in abstract form (Circulation. 2007;116[suppl II]:II-22)
Keywords:vasculotropin, very late activation antigen 4, angiogenesis, animal experiment, animal model, animal tissue, article, bioluminescence, CD34 selection, cell survival, cell therapy, controlled study, endothelium cell, heart function, heart infarction, heart left ventricle, heart left ventricle ejection fraction, heart muscle cell, heart ventricle wall, human, human cell, molecular imaging, mouse, muscle development, nonhuman, nuclear magnetic resonance imaging, paracrine signaling, priority journal, SCID mouse, survival time, Animals, Antigens, CD34, Disease Models, Animal, Female, Heart, Humans, Magnetic Resonance Imaging, Mice, Mice, SCID, Myocardial Infarction, Myocardium, Neovascularization, Physiologic, Positron-Emission Tomography, Stroke Volume, Survival Rate, T-Lymphocytes, Tissue Therapy, Tomography, X-Ray Computed
Divisions:College of Science > School of Computer Science
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ID Code:24135
Deposited On:07 Apr 2017 10:47

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