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