title: The globoseries glycosphingolipid SSEA-4 is a marker of bone marrow-derived clonal multipotent stromal cells in vitro and in vivo.
abstract: The therapeutic potential of multipotent stromal cells (MSC) may be enhanced by the identification of markers that allow their discrimination and enumeration both in vivo and in vitro. Here, we investigated the ability of embryonic stem cell-associated glycosphingolipids to isolate human MSC from both whole-bone-marrow (BM) and stromal cell cultures. Only SSEA-4 was consistently expressed on cells within the CD45loCD105hi marrow fraction and could be used to isolate cells with the capacity to give rise to stromal cultures containing MSC. Human stromal cultures, generated in either the presence or absence of serum, contained heterogeneous cell populations discriminated by the quantity of SSEA-4 epitopes detected on their surface. A low level of surface SSEA-4 (SSEA-4lo) correlated with undetectable levels of the α2,3-sialyltransferase-II enzyme required to synthesize SSEA-4; a reduced proliferative potential; and the loss of fat-, bone-, and cartilage-forming cells during long-term culture. In vitro, single cells with the capacity to generate multipotent stromal cultures were detected exclusively in the SSEA-4hi fraction. Our data demonstrate that a high level of surface epitopes for SSEA-4 provides a definitive marker of MSC from human BM.
authors: Biologics and Genetic Therapies Directorate, Health Products and Food Branch , Health Canada, Ottawa, Canada. michael.rosu-myles@hc-sc.gc.ca
authors: Michael
authors: M
authors: Rosu-Myles
authors: Jennifer
authors: J
authors: McCully
authors: Joel
authors: J
authors: Fair
authors: Jelica
authors: J
authors: Mehic
authors: Pablo
authors: P
authors: Menendez
authors: Rene
authors: R
authors: Rodriguez
authors: Carole
authors: C
authors: Westwood
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D000939:Epitopes / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D000939:Epitopes; D055746:Stage-Specific Embryonic Antigens; C066584:stage-specific embryonic antigen-4