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␣ (SDF-1␣) and its mobilizing effects on BM. Blocking SDF-1␣ activity with neutralizing antibodies abrogated BMderived neovascularization in lung cancer and retinopathy. IntroductionThe mechanisms governing bone marrow (BM)-derived contribution to tissue neovascularization and the origin of marrow cells participating in this process are undefined, and remain a root of controversy in the field. Although initially thought to arise from local angiogenic events, recent studies purport that BM-derived cells including endothelial progenitor cells, hemangiocytes, and hemangioblasts contribute directly to vessel formation in different models of neovascularization. [1][2][3][4][5][6][7][8][9][10] However, contradictory results relegate BM involvement to paracrine mechanisms rather than direct vessel contribution through the action of cells such as tie-2 expressing monocytes (TEMs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and recruited blood circulating cells (RBCCs). [11][12][13][14][15][16][17][18][19] Moreover, it was recently reported that BM-derived endothelial progenitor cells expressing vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2 ϩ ) are not mobilized from BM in a mouse model of cancer. 14 Several reports indicate the importance of timing and environment on BM-derived neovascularization in cancer. 2,5,20,21 These results coupled with different model systems and experimental techniques may explain confounding results.Therefore, we reasoned that we could test various situations of neovessel formation using a novel technique in which multiple neovascularization models were established in individual mice. This technique reduced experimental variations and allowed direct comparative analyses among models.Our data suggest that neovascularization can occur through multiple redundant mechanisms dictated by the local microenvironment. BM-derived cells can participate in neovascularization in some but not all settings. BM contribution is dependent on site-specific expression of stromal cell derived factor-1␣ (SDF-1␣), its mobilizing effects on BM, and its capacity to promote homing of those mobilized cells to specific tissues. Furthermore, we show that SDF-1␣ activity can be significantly inhibited by therapeutic intervention, thereby reducing BM contribution to neovascularization. We also confirm the adult hematopoietic stem cell (HSC) as a long-t...

A 52-year-old Hispanic female with a medical history of rosacea and extensive sun exposure presented with a nonhealing erosion on her left nasal crease. The lesion had been present for approximately 3 to 4 weeks and was slightly tender. She did not use any oral or topical prescriptions or any over-the-counter medications. Additionally, she denied recent procedures or trauma to the region.A pincer nail deformity can be characterized as an increase in transverse curvature along the longitudinal axis of the nail. This curvature increases from the proximal to distal aspect, leading to pinching of the involved digits, giving the nail a trumpet-like appearance. 1 Major indications for treatment are pain, discomfort wearing shoes, and cosmetic embarrassment.