Canadian Journal of Cardiology
Review| Volume 35, ISSUE 10, P1311-1321, October 2019

CD34+ Stem Cells: Promising Roles in Cardiac Repair and Regeneration

  • Tina Binesh Marvasti
    Toronto General Hospital Research Institute, Division of Cardiovascular Surgery, University Health Network, Toronto, Ontario, Canada
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  • Faisal J. Alibhai
    Toronto General Hospital Research Institute, Division of Cardiovascular Surgery, University Health Network, Toronto, Ontario, Canada
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  • Richard D. Weisel
    Toronto General Hospital Research Institute, Division of Cardiovascular Surgery, University Health Network, Toronto, Ontario, Canada

    Division of Cardiac Surgery, Department of Surgery, University of Toronto; Toronto, Ontario, Canada
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  • Ren-Ke Li
    Corresponding author: Dr Ren-Ke Li, Toronto Medical Discovery Tower, Room 3-702, 101 College St, Toronto, Ontario M5G 1L7, Canada. Tel.: +1-416-581-7492; fax: +1-416-581-7493.
    Toronto General Hospital Research Institute, Division of Cardiovascular Surgery, University Health Network, Toronto, Ontario, Canada

    Division of Cardiac Surgery, Department of Surgery, University of Toronto; Toronto, Ontario, Canada
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      Cell therapy has received significant attention as a novel therapeutic approach to restore cardiac function after injury. CD34-positive (CD34+) stem cells have been investigated for their ability to promote angiogenesis and contribute to the prevention of remodelling after infarct. However, there are significant differences between murine and human CD34+ cells; understanding these differences might benefit the therapeutic use of these cells. Herein we discuss the function of the CD34 cell and highlight the similarities and differences between murine and human CD34 cell function, which might explain some of the differences between the animal and human evolutions. We also summarize the studies that report the application of murine and human CD34+ cells in preclinical studies and clinical trials and current limitations with the application of cell therapy for cardiac repair. Finally, to overcome these limitations we discuss the application of novel humanized rodent models that can bridge the gap between preclinical and clinical studies as well as rejuvenation strategies for improving the quality of old CD34+ cells for future clinical trials of autologous cell transplantation.


      Le traitement par des cellules souches attire beaucoup d’attention comme démarche thérapeutique novatrice dans le rétablissement de la fonction cardiaque à la suite d’une lésion. Les cellules souches CD34 (CD34+) ont été étudiées en vue d’évaluer leur capacité à promouvoir l’angiogenèse et à contribuer à la prévention du remodelage cardiaque après un infarctus. Toutefois, les différences sont marquées entre les cellules CD34+ murines et humaines; comprendre ces différences pourrait être utile dans l’usage thérapeutique de ces cellules. Dans cet article, nous traitons de la fonction des cellules CD34 et mettons en évidence les similarités et les différences entre les fonctions des cellules CD34 murines et humaines, lesquelles pourraient expliquer certaines des variations entre les évolutions humaines et animales. Nous offrons aussi un résumé des études qui traitent de l’usage des cellules CD34+ humaines et murines pendant des études précliniques et des essais cliniques ainsi que de leurs limites actuelles dans la réparation des lésions cardiaques. Finalement, pour surmonter ces limites, nous discutons de l’application de nouveaux modèles humanisés de rongeurs qui pourraient combler l’écart entre les études précliniques et cliniques. Nous discutons également des stratégies de renouvellement permettant d’améliorer la qualité des cellules CD34+ vieillissantes en vue d’études ultérieures sur la transplantation de cellules souches autologues.
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      Linked Article

      • Paracrine Heart Repair Comes of Age
        Canadian Journal of CardiologyVol. 35Issue 10
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          For almost 20 years, cell therapy has been touted as a natural solution to replace heart muscle lost at the time of myocardial infarction.1-3 But recent scandals4 and failed clinical trials5 have done little to inspire confidence in a jaded medical community. Although a portion of the blame lies in the early hype and hyperbole raising unrealistic expectations, some of the initial mechanisms that assumed how transplanted cells would modify heart function have proved to be spectacularly wrong and prompted many to consider new directions to restore injured tissue.
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