Contribution of endothelial progenitors and proangiogenic hematopoietic cells to vascularization of tumor and ischemic tissue.
OBJECTIVE
During the last several years, a substantial amount of evidence from animal as well as human studies has advanced our knowledge of how bone marrow derived cells contribute to neoangiogenesis. In the light of recent findings, we may have to redefine our thinking of endothelial cells as well as of perivascular mural cells.


RESULTS
Inflammatory hematopoietic cells, such as macrophages, have been shown to promote neoangiogenesis during tumor growth and wound healing. Dendritic cells, B lymphocytes, monocytes, and other immune cells have also been found to be recruited to neoangiogenic niches and to support neovessel formation. These findings have led to the concept that subsets of hematopoietic cells comprise proangiogenic cells that drive adult revascularization processes. While evidence of the importance of endothelial progenitor cells in adult vasculogenesis increased further, the role of these comobilized hematopoietic cells has been intensely studied in the last few years.


CONCLUSIONS
Angiogenic factors promote mobilization of vascular endothelial growth factor receptor 1-positive hematopoietic cells through matrix metalloproteinase-9 mediated release of soluble kit-ligand and recruit these proangiogenic cells to areas of hypoxia, where perivascular mural cells present stromal-derived factor 1 (CXCL-12) as an important retention signal. The same factors are possibly involved in mobilization of vascular endothelial growth factor receptor 2-positive endothelial precursors that may participate in neovessel formation. The complete characterization of mechanisms, mediators and signaling pathways involved in these processes will provide novel targets for both anti and proangiogenic therapeutic strategies.
Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Medical College of Cornell University, New York 10021, USA.
Hans-Georg
HG
Kopp
Carlos A
CA
Ramos
Shahin
S
Rafii
D000818:Animals; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D009369:Neoplasms / Q000098:blood supply* / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; D040281:Vascular Endothelial Growth Factor Receptor-1