Towards in situ tissue repair: human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2.
The recruitment of bone marrow CD34- mesenchymal stem- and progenitor cells (MSC) and their subsequent differentiation into distinct tissues is the precondition for in situ tissue engineering. The objective of this study was to determine the entire chemokine receptor expression profile of human MSC and to investigate their chemotactic response to the selected chemokines CCL2, CXCL8 and CXCL12. Human MSC were isolated from iliac crest bone marrow aspirates and showed a homogeneous population presenting a typical MSC-related cell surface antigen profile (CD14-, CD34-, CD44+, CD45-, CD166+, SH-2+). The expression profile of all 18 chemokine receptors was determined by real-time PCR and immunohistochemistry. Both methods consistently demonstrated that MSC express CC, CXC, C and CX(3)C receptors. Gene expression and immunohistochemical analysis documented that MSC express chemokine receptors CCR2, CCR8, CXCR1, CXCR2 and CXCR3. A dose-dependent chemotactic activity of CXCR4 and CXCR1/CXCR2 ligands CXCL12 and CXCL8 (interleukin-8) was demonstrated using a 96-well chemotaxis assay. In contrast, the CCR2 ligand CCL2 (monocyte chemoattractant protein-1, MCP-1) did not recruited human MSC. In conclusion, we report that the chemokine receptor expression profile of human MSC is much broader than known before. Furthermore, for the first time, we demonstrate that human MSC migrate upon stimulation with CXCL8 but not CCL2. In combination with already known data on MSC recruitment and differentiation these are promising results towards in situ regenerative medicine approaches based on guiding of MSC to sites of degenerated tissues.
Ringe
Jochen
J
Tissue Engineering Laboratory, Department of Rheumatology, Charité-University Medicine Berlin, Berlin, Germany. jochen.ringe@charite.de
Strassburg
Sandra
S
Neumann
Katja
K
Endres
Michaela
M
Notter
Michael
M
Burmester
Gerd-Rüdiger
GR
Kaps
Christian
C
Sittinger
Michael
M
D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007085:Ilium / Q000166:cytology; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000494:pharmacology*; D008024:Ligands; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism*
C515334:CCR2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D008024:Ligands; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B