Characterization and functionality of cell surface molecules on human mesenchymal stem cells.
We have characterized adhesion molecules on the surface of multipotential human mesenchymal stem cells (hMSCs) and identified molecules whose ligands are present on mature hematopoietic cells. Flow cytometric analysis of hMSCs identified the expression of integrins: alpha1, alpha2, alpha3, alpha5, alpha6, alphav, beta1, beta3, and beta4, in addition to ICAM-1, ICAM-2, VCAM-1, CD72, and LFA-3. Exposure of hMSCs to IL-1alpha, TNFalpha or IFNgamma up-modulated ICAM-1 surface expression, whereas only IFNgamma increased both HLA-class I and -class II molecules on the cell surface. Whole cell-binding assays between the hMSCs and hematopoietic cell lines showed that T lymphocytic lines bound hMSCs with higher affinity than lines of either B lymphocytes or those of myeloid lineage. Experiments using autologous T lymphocytes isolated from peripheral blood mononuclear cells showed that hMSCs exhibited increased affinity for activated T-lymphocytes compared to resting T cells by quantitative whole cell binding and rosetting assays. Flow cytometric analysis of rosetted cells demonstrated that both CD4+ and CD8+ cells bound to hMSCs. To determine the functional significance of these findings, we tested the ability of hMSCs to present antigen to T lymphocytes. hMSCs pulsed with tetanus toxoid stimulated proliferation and cytokine production (IL-4, IL-10, and IFNgamma) in a tetanus-toxoid-specific T cell line. Maximal cytokine production correlated with maximal antigen-dependent proliferation. These data demonstrate physiological outcome as a consequence of interactions between hMSCs and human hematopoietic lineage cells, suggesting a role for hMSCs in vivo to influence both hematopoietic and immune function(s).
Majumdar
Manas K
MK
Osiris Therapeutics, Inc, Baltimore, Md, USA.
Keane-Moore
Michele
M
Buyaner
Diana
D
Hardy
Wayne B
WB
Moorman
Mark A
MA
McIntosh
Kevin R
KR
Mosca
Joseph D
JD
D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism*; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism; D008024:Ligands; D008648:Mesoderm / Q000378:metabolism; D008875:Middle Aged; D009841:Oligonucleotides / Q000737:chemistry; D010641:Phenotype; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D013601:T-Lymphocytes / Q000378:metabolism
D016827:CD8 Antigens; D016207:Cytokines; D016023:Integrins; D008024:Ligands; D009841:Oligonucleotides; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma