Expression of vascular cell adhesion molecule-1 indicates the differentiation potential of human bone marrow stromal cells

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Abstract

Bone marrow stromal cells (BMSCs) are a mixture of cells differing in differentiation potential including mesenchymal stem cells, and so far no CD antigens were found to be predictable for the differentiation property of each BMSC. Here we attempted to isolate differentiation-associated CD antigens using 100 immortalized human BMSC (ihBMSC) clones. Among 13 CD antigens analyzed, only CD106/Vascular cell adhesion molecule-1 (VCAM-1) showed a clear correlation with the differentiation potential of each clone; CD106-positive ihBMSC clones were less osteogenic and more adipogenic than CD106-negative clones. This association was confirmed in primary BMSCs sorted by CD106, showing that the CD106-positive fraction contained less osteogenic and more adipogenic cells than the CD106-positive fraction. The evaluation of CD106 fraction of BMSC strains in early passages predicted clearly the osteogenic and adipogenic potential after in vitro induction of differentiation, indicating the usefulness of CD106 as a differentiation-predicting marker of BMSC.

Section snippets

Cells and tissue samples

ihBMSCs were established by sequential transduction of the hTERT and Bmi1 genes [13], and cultured in Dulbecco’s modified Eagle’s medium (DMEM, Sigma–Aldrich, St. Louis, MI) with 10% fetal bovine serum (FBS, Hyclone, South Logan, UT). Subcloning of ihBMSCs was performed by limited dilution, and 100 clones were established and cultured under the same conditions.

Primary human BMSCs (designated as huBM) were isolated from the bone marrow taken from iliac crests of donors, who received orthopedic

Heterogeneous differentiation potential of ihBMSC clones

One hundred single-cell derived clones were established from the parental ihBMSC by limited dilution. No significant difference was observed among clones in terms of growth potential (data not shown). The adipogenic, osteogenic, and chondrogenic potential of each clone was determined by the standard induction method and categorized as either positive or negative based on the definition described in Materials and methods section. Five clones showed tri-directional differentiation, and 78 clones

Discussion

CD106/VCAM-1 is a cell surface glycoprotein, which binds to the α4β1 and α4β7 integrins [19]. A deficiency of CD106/VCAM-1 results in embryonic death with the absence of chorion-allantois fusion or multiple abnormalities in the heart in mice, but no significant abnormality was found in mesenchymal tissues during the embryonic stage [20]. CD106/VCAM-1 is associated with homing of HSCs, and CD106/VCAM-1-positive BMSCs, which may be MSCs, keep HSCs in their niche [21], [22]. The binding to

Acknowledgments

The authors thank Drs. Koichi Nishijo, and Tatsuya Ishibe for advice, and Drs. Takeshi Sakamoto and Hiromu Ito for clinical samples. This work was supported by the New Energy and Industrial Technology Development Organization (NEDO) with a project entitled Development of Evaluation Technology for Early Introduction of Regenerative Medicine, and also by Grants-in-aid for Scientific Research from the Japan Society for the Promotion of Science, from the Ministry of Education, Culture, Sports,

References (26)

  • M.F. Pittenger et al.

    Multilineage potential of adult human mesenchymal stem cells

    Science

    (1999)
  • E.M. Horwitz et al.

    Isolated allogenic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone

    Proc. Natl. Acad. Sci. USA

    (2002)
  • H. Aslan et al.

    Osteogenic differentiation of noncultured immunoisolated bone marrow-derived CD105+ cells

    Stem Cells

    (2006)
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