Abstract
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.
Résumé
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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Article info
Publication history
Published online: June 10, 2019
Accepted:
May 27,
2019
Received:
January 27,
2019
Footnotes
See editorial by Davis, pages 1278–1280 of this issue.
See page 1318 for disclosure information.
Identification
Copyright
© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Paracrine Heart Repair Comes of AgeCanadian Journal of CardiologyVol. 35Issue 10
- PreviewFor 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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