Gene expression profiling of human mesenchymal stem cells chemotactically induced with CXCL12.
In situ tissue engineering is a promising approach in regenerative medicine, with the possibility that adult stem or progenitor cells will be guided chemotactically to a tissue defect and subsequently differentiate into the surrounding tissue type. Mesenchymal stem cells (MSC) represent attractive candidate cells. Chemokines such as CXCL12 (SDF-1alpha) chemoattract MSC, but little is known about the molecular processes involved in the chemotaxis and migration of MSC. In this study, MSC recruitment by CXCL12 was investigated by genome-wide microarray analysis. The dose-dependent migration potential of bone-marrow-derived MSC toward CXCL12 was measured in an in vitro assay, with a maximum being recorded at a concentration of 1,000 nM CXCL12. Microarray analysis of MSC stimulated with CXCL12 and non-stimulated controls showed 30 differentially expressed genes (24 induced and six repressed). Pathway analysis revealed 11 differentially expressed genes involved in cellular movement and cytokine-cytokine receptor interaction, including those for migratory inducers such as the chemokines CXCL8 and CCL26, the leukocyte inhibitory factor, secretogranin II, and prostaglandin endoperoxide synthase 2. These results were confirmed by real-time polymerase chain reaction for selected genes. The obtained data provide further insights into the molecular mechanisms involved in chemotactic processes in cell migration and designate CXCL12 as a promising candidate for in situ recruitment in regenerative therapies.
Stich
Stefan
S
Tissue Engineering Laboratory and Berlin-Brandenburg Center for Regenerative Therapies, Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Berlin, Germany.
Haag
Marion
M
Häupl
Thomas
T
Sezer
Orhan
O
Notter
Michael
M
Kaps
Christian
C
Sittinger
Michael
M
Ringe
Jochen
J
D000328:Adult; D002469:Cell Separation; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D016000:Cluster Analysis; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054377:Chemokine CXCL12