A novel function for the haemopoietic supportive murine bone marrow MS-5 mesenchymal stromal cell line in promoting human vasculogenesis and angiogenesis.
The bone marrow contains specific microenvironmental stem cell niches that maintain haemopoiesis. CXCL12-expressing mesenchymal stromal cells are closely associated with the bone marrow sinusoidal endothelia, forming key elements of the haemopoietic stem cell niche, yet their ability to regulate endothelial function is not clearly defined. Given that the murine nestin(+)  cell line, MS-5, provides a clonal surrogate bone marrow stromal niche capable of regulating both murine and human primitive haemopoietic stem/progenitor cell (HSC/HPC) fate in vitro, we hypothesized that MS-5 cells might also support new blood vessel formation and function. Here, for the first time, we demonstrate that this is indeed the case. Using proteome arrays, we identified HSC/HPC active angiogenic factors that are preferentially secreted by haemopoietic supportive nestin(+) MS-5 cells, including CXCL12 (SDF-1), NOV (CCN3), HGF, Angiopoietin-1 and CCL2 (MCP-1). Concentrating on CXCL12, we confirmed its presence in MS-5 conditioned media and demonstrated that its antagonist in receptor binding, AMD-3100, which mobilizes HSC/HPCs and endothelial progenitors from bone marrow, could significantly reduce MS-5 mediated human vasculogenesis in vitro, principally by regulating human endothelial cell migration. Thus, the clonal nestin(+) MS-5 murine bone marrow stromal cell line not only promotes human haemopoiesis but also induces human vasculogenesis, with CXCL12 playing important roles in both processes.
Stem Cell Research Laboratory, NHS Blood and Transplant, John Radcliffe Hospital, Headington, Oxford, UK.
Bob
B
Zhou
Grigorios
G
Tsaknakis
Kate E
KE
Coldwell
Cheen P
CP
Khoo
Maria G
MG
Roubelakis
Chao-Hui
CH
Chang
Emma
E
Pepperell
Suzanne M
SM
Watt
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism / Q000502:physiology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D040901:Proteomics / Q000379:methods
D043925:Angiogenesis Inducing Agents; D054377:Chemokine CXCL12; D017077:Culture Media, Conditioned; C515256:Cxcl12 protein, mouse