Expression of Integrin α2 Receptor in Human Cord Blood CD34+CD38−CD90+ Stem Cells Engrafting Long-Term in NOD/SCID-IL2Rγcnull Mice

Authors

  • Wan Man Wong,

    1. Hematopoietic Stem Cell Laboratory, Department of Laboratory Medicine, Lund University, Lund, Sweden
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  • Mikael Sigvardsson,

    1. Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
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  • Ingbritt ÅStrand-Grundström,

    1. Hematopoietic Stem Cell Laboratory, Department of Laboratory Medicine, Lund University, Lund, Sweden
    2. Hematology Department, Skåne University Hospital, Lund, Sweden
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  • Donna Hogge,

    1. Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada
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  • Jonas Larsson,

    1. Molecular Medicine and Gene therapy, Department of Laboratory Medicine, Lund University, Lund, Sweden
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  • Hong Qian,

    1. Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
    2. Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden
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  • Marja Ekblom

    Corresponding author
    1. Hematopoietic Stem Cell Laboratory, Department of Laboratory Medicine, Lund University, Lund, Sweden
    2. Hematology Department, Skåne University Hospital, Lund, Sweden
    • Hematopoietic Stem Cell Laboratory, Department of Laboratory Medicine, Lund University, 22184 Lund, Sweden
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    • Tel.: +46462220804; Fax: +46462223600


  • Author contributions: W.M.W.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of the manuscript; M.S.: conception and design, data analysis and interpretation, manuscript writing, and final approval of the manuscript; I.Å.-G.: collection and assembly of data and final approval of the manuscript; D.H. and J. L.: provision of study material, data analysis and interpretation, and final approval of the manuscript; H.Q. and M.E.: conception and design, financial support, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of the manuscript. H.Q. and M. E. contributed equally to this article.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • First published online in STEM CELLSEXPRESS November 16, 2012.

Abstract

Human hematopoietic stem cells reside in the CD34+CD38−CD90+ population in cord blood and bone marrow. However, this cell fraction is heterogeneous, and the phenotype of the rare primitive stem cells remains poorly defined. We here report that primitive cord blood CD34+CD38−CD90+ stem cells, with the ability to reconstitute NOD/SCID-IL2Rγcnull (NSG) mice long-term, at 24 weeks after transplantation, can be prospectively isolated at an increased purity by using integrin α2 receptor as an additional stem cell marker. Using a limiting dilution transplantation assay, we found a highly significant enrichment of multilineage reconstituting stem cells in the CD34+CD38−CD90+ cell fraction expressing the integrin α2 receptor, with a frequency of 1/29 cells, as compared to a frequency of 1/157 in the corresponding integrin α2− cells. In line with this, long-term reconstituting stem cells within the cord blood CD34+CD38− cell population were significantly enriched in the integrin α2+ fraction, while stem cells and progenitors reconstituting short-term, at 8–12 weeks, were heterogeneous in integrin α2 expression. Global gene expression profiling revealed that the lineage-marker negative (Lin−) CD34+CD38−CD90+CD45RA− integrin α2+ cell population was molecularly distinct from the integrin α2− cell population and the more mature Lin−CD34+CD38−CD90−CD45RA− cell population. Our findings identify integrin α2 as a novel stem cell marker, which improves prospective isolation of the primitive human hematopoietic stem cells within the CD34+CD38−CD90+ cell population for experimental and therapeutic stem cell applications. STEM CELLS2013;31:360–371

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