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J Thorac Cardiovasc Surg 2010;140:216-224
© 2010 The American Association for Thoracic Surgery

Evolving Technology/Basic Science

In vitro functional comparison of therapeutically relevant human vasculogenic progenitor cells used for cardiac cell therapy

Yan Zhang, MD, MSca,b,*, Serena Wong, BSca,b,*, Jessica Laflèche, BSca,b, Suzanne Crowea, Thierry G. Mesana, MD, PhDa, Erik J. Suuronen, PhDa,b,*, Marc Ruel, MD, MPHa,b,*

a Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
b Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada

Received for publication June 30, 2009; revisions received October 15, 2009; accepted for publication November 3, 2009.

* 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. (Email: esuuronen{at}ottawaheart.ca; mruel{at}ottawaheart.ca).

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.

Abbreviations and Acronyms BM = bone marrow; CAD = coronary artery disease; EBM-2 = endothelial basal medium 2; EPC = endothelial progenitor cell; GRO = growth-related oncogene; HUVEC = human umbilical vein endothelial cell; IL = interleukin; MCP = monocyte chemoattractant protein; MNC = mononuclear cell; MSC = mesenchymal stem cell; PB = peripheral blood; RANTES = regulated upon activation, normal T-cell expressed and secreted; VEGF = vascular endothelial growth factor; VEGFR-2 = vascular endothelial growth factor receptor 2




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