期刊
BLOOD
卷 114, 期 19, 页码 4310-4319出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-03-211342
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资金
- National Institute of Diabetes and Digestive and Kidney Diseases [K08 DK067359]
- Department of Health James & Esther King Biomedical Research Program
- National Heart, Lung, and Blood Institute [R01 HL070738, R01 HL075258]
- National Cancer Institute (NCI) Public Health Service (PHS) [CA084408, CA089655]
Adult bone marrow (BM) contributes to neovascularization in some but not all settings, and reasons for these discordant results have remained unexplored. We conducted novel comparative studies in which multiple neovascularization models were established in single mice to reduce variations in experimental methodology. In different combinations, BM contribution was detected in ischemic retinas and, to a lesser extent, Lewis lung carcinoma cells, whereas B16 melanomas showed little to no BM contribution. Using this spectrum of BM contribution, we demonstrate the necessity for site-specific expression of stromal-derived factor-1 alpha (SDF-1 alpha) and its mobilizing effects on BM. Blocking SDF-1 alpha activity with neutralizing antibodies abrogated BM-derived neovascularization in lung cancer and retinopathy. Furthermore, secondary transplantation of single hematopoietic stem cells (HSCs) showed that HSCs are a long-term source of neovasculogenesis and that CD133(+)CXCR4(+) myeloid progenitor cells directly participate in new blood vessel formation in response to SDF-1(+). The varied BM contribution seen in different model systems is suggestive of redundant mechanisms governing postnatal neovasculogenesis and provides an explanation for contradictory results observed in the field. (Blood. 2009; 114:4310-4319)
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