Molecular trafficking mechanisms of multipotent mesenchymal stem cells derived from human bone marrow and placenta.
We compared potential trafficking mechanisms used by human (h) multipotent mesenchymal stem cells (MSC) derived from bone marrow (bm) or placenta (p). Both hbmMSC and hpMSC expressed a broad range of cell surface adhesion molecules including beta1-integrins (CD29) and CD44. Array data showed that both hbmMSC and hpMSC expressed mRNA for the cell adhesion molecules CD54 (ICAM-1), E-cadherin, CD166 (ALCAM), CD56 (NCAM), CD106 (VCAM-1), CD49a, b, c, e and f (integrins alpha1, 2, 3, 4 and 6), integrin alpha11, CD51 (integrin alphaV), and CD29 (integrins beta1). Functional binding of hpMSC, but not hbmMSC to VCAM-1 was demonstrated using recombinant chimeric constructs. Neither bone marrow nor placental MSC expressed ligands to endothelial selectins such as PSGL-1 or sialyl Lewis X (sLe(x)) carbohydrates and neither were able to bind functionally to chimeric constructs of the endothelial selectins CD62E (E-selectin) and CD62P (P-selectin). Furthermore, MSC expressed a restricted range of transferases necessary for expression of sLe(x), with no detectable expression of fucosyl transferases IV or VII. Placental MSC, but not hbmMSC, expressed mRNA for the chemokine receptors CCR1 and CCR3, and both hbmMSC and hpMSC expressed mRNA for CCR7, CCR8, CCR10, CCR11, CXCR4 and CXCR6. Intracellular chemokine receptor protein expression of CCR1, CCR3, CXCR3, CXCR4 and CXCR6 was detected in both hbmMSC and hpMSC. Cell surface expression of chemokine receptors was much more restricted with only CXCR6 displaying a strong signal on hbmMSC and hpMSC. Although cell surface expression of CXCR4 was not detected, MSC migrated in response to its ligand, CXCL12 (SDF-1). Thus, hbmMSC and hpMSC have an almost identical profile for cell surface adhesion and chemokine receptor molecules at the mRNA and protein levels. However, at the functional level, hpMSC likely utilise VLA-4-mediated binding in a superior manner to hbmMSC and thus may have superior engraftment properties to hbmMSC in vivo.
Adult Stem Cell and Haematopoietic Stem Cell Laboratories, Mater Medical Research Institute, Brisbane, Queensland, Australia.
Gary
G
Brooke
Hui
H
Tong
Jean-Pierre
JP
Levesque
Kerry
K
Atkinson
D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005643:Fucose / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D016695:Glycosyltransferases / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D010641:Phenotype; D010920:Placenta / Q000166:cytology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D019087:Selectins / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D054377:Chemokine CXCL12; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D019087:Selectins; D019010:Vascular Cell Adhesion Molecule-1; D005643:Fucose; D016695:Glycosyltransferases