Human periosteum-derived progenitor cells express distinct chemokine receptors and migrate upon stimulation with CCL2, CCL25, CXCL8, CXCL12, and CXCL13.
For bone repair, transplantation of periosteal progenitor cells (PCs), which had been amplified within supportive scaffolds, is applied clinically. More innovative bone tissue engineering approaches focus on the in situ recruitment of stem and progenitor cells to defective sites and their subsequent use for guided tissue repair. Chemokines are known to induce the directed migration of bone marrow CD34(-) mesenchymal stem cells (MSCs). The aim of our study was to determine the chemokine receptor expression profile of human CD34(-) PCs and to demonstrate that these cells migrate upon stimulation with selected chemokines. PCs were isolated from periosteum of the mastoid bone and displayed a homogenous cell population presenting an MSC-related cell-surface antigen profile (ALCAM(+), SH2(+), SH3(+), CD14(-), CD34(-), CD44(+), CD45(-), CD90(+)). The expression profile of chemokine receptors was determined by real-time PCR and immunohistochemistry. Both methods consistently demonstrated that PCs express receptors of all four chemokine subfamilies CC, CXC, CX(3)C, and C. Migration of PCs and a dose-dependent migratory effect of the chemokines CCL2 (MCP1), CCL25 (TECK), CXCL8 (IL8), CXCL12 (SDF1alpha), and CXCL13 (BCA1), but not CCL22 (MDC) were demonstrated using a 96-multiwell chemotaxis assay. In conclusion, for the first time, here we report that human PCs express chemokine receptors, present their profile, and demonstrate a dose-dependent migratory effect of distinct chemokines on these cells. These results are promising towards in situ bone repair therapies based on guiding PCs to bone defects, and encourage further in vivo studies.
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. stefan.stich@charite.de
Loch
Alexander
A
Leinhase
Iris
I
Neumann
Katja
K
Kaps
Christian
C
Sittinger
Michael
M
Ringe
Jochen
J
D000328:Adult; D053687:Adult Stem Cells / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D002465:Cell Movement; D002469:Cell Separation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D054382:Chemokine CXCL13 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism; D008416:Mastoid / Q000166:cytology / Q000276:immunology*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010521:Periosteum / Q000166:cytology / Q000276:immunology*; D016133:Polymerase Chain Reaction; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016209:Interleukin-8; D019707:Receptors, Chemokine