Generation of CD133+ cells from CD133- peripheral blood mononuclear cells and their properties

doi:10.1016/j.cardiores.2006.01.014

Cardiovascular Research 2006 70(1):126-135; doi:10.1016/j.cardiores.2006.01.014

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Generation of CD133⁺ cells from CD133^– peripheral blood mononuclear cells and their properties

Erik J. Suuronen^a, Serena Wong^a^,c, Varun Kapila^a, Geeta Waghray^a, Stewart C. Whitman^b^,c, Thierry G. Mesana^a and Marc Ruel^a^,c^,*

^aDivision of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7
^bPathology and Laboratory Medicine, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7
^cCellular and Molecular Medicine, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7

^* Corresponding author. Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7. Tel.: +1 613 761 4893; fax: +1 613 761 5367. Email address: mruel{at}ottawaheart.ca

Objective CD133 may be the most specific marker of endothelialprogenitor cells (EPCs), which are thought to be largely confinedto the bone marrow milieu. This study reports on the phenotypiccharacterization and functional analysis of human CD133⁺ cellsand their generation from cells in the peripheral circulation.

Methods Adult human CD133⁺ and CD133^– cells were isolatedfrom peripheral blood mononuclear cells, and the generationof CD133⁺ cells in culture was attempted using different culturecombinations. The phenotypic, migratory, adhesive, and angiogenicproperties of the native and generated populations were investigated.

Results In adherent and in suspension culture systems, CD133⁺cells also expressing CD34 and VEGFR-2 were successfully derivedfrom a previously CD133^– population. The migratory potentialof CD133⁺ cells was enhanced by the presence of the CD133^–cells. Also, the CD133⁺ cells derived from the CD133^–cells demonstrated improved adhesion to extracellular matrixand endothelial monolayer substrates, and their contributionto in vitro angiogenesis was enhanced compared to freshly isolatedCD133⁺ cells.

Conclusions These results demonstrate a source of blood CD133⁺cells other than direct mobilization from the bone marrow. Cellularinteraction was observed between fractions, with CD133⁺ cellsshowing better in vitro function in the presence of CD133^–cells. These findings provide a novel source for CD133⁺ cellsand a rationale for the investigation of angiogenic cell recruitmentor delivery strategies involving more than one cell type atischemic sites.

KEYWORDS Angiogenesis; Cell differentiation; Stem cells

Time for primary review 19 days

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Cardiovascular Research

Generation of CD133+ cells from CD133– peripheral blood mononuclear cells and their properties

Generation of CD133⁺ cells from CD133^– peripheral blood mononuclear cells and their properties