In vitro functional comparison of therapeutically relevant human vasculogenic progenitor cells used for cardiac cell therapy
Received 30 June 2009; received in revised form 15 October 2009; accepted 3 November 2009. published online 18 February 2010.
Objective
In cardiac cell therapy almost every cell type tested experimentally has yielded some benefit. However, there is a lack of studies directly comparing the function of various stem/progenitor cell populations. This study describes the expansion of peripheral blood CD133+ cells and compares their functional properties with those of other commonly used human progenitor cell populations.
Methods
CD133+ cells were generated from the CD133− fraction of peripheral blood, either serially (pooled–derived) or after 14 days of culture (derived). Their phenotypic, migratory, and vasculogenic properties were compared with those of 4 commonly used progenitor cell populations in vitro.
Results
Serial expansion resulted in an 11-fold increase in the number of CD133+ cells. The proportion of derived CD133+ cells collected between 0 and 8 days also expressing CD34 and vascular endothelial growth factor receptor 2 was similar (approximately 60%, P=.41). Adherent, 4-day cultured endothelial progenitor cells demonstrated enhanced migration compared with each of the other 5 cell populations (all P ≤ .002). The migration of derived CD133+ progenitors was enhanced by coculture with CD133− cells or their supernatant (P < .05). In vitro vasculogenesis assays revealed that derived and pooled–derived CD133+ cells had superior vasculogenic potential compared with other progenitor populations (P ≤ .03).
Conclusions
A novel source of expandable CD133+ cells can be generated from the CD133− fraction of peripheral blood. The CD133 phenotypic marker translates into the cell being vasculogenically more potent in vitro, which could be beneficial to inducing vasculogenesis in the ischemic heart. Furthermore, intercellular interactions appear important for improving the therapeutic efficacy of cell transplantation.
aDivision of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
bDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada
Address for reprints: Marc Ruel, MD, MPH, and Erik J. Suuronen, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin St, Ottawa, Ontario, K1Y 4W7, Canada.
Supported by the Canadian Institutes of Health Research (to Drs Ruel and Suuronen, grant MOP-77536), by the Canadian Foundation for Innovation (to Dr Ruel, award 7346), and by the Heart and Stroke Foundation of Canada Doctoral Research Award (to Dr Zhang).
Disclosures: None.
∗ Y. Zhang and S. Wong contributed equally to this work.
ABSTRACT