內皮前驅細胞為一群具有分化為成熟內皮細胞能力之前驅細胞，並促進胚胎及缺氧的組織中新血管的生成。另外，許多研究也指出內皮前驅細胞具有治療心血管疾病之潛力。然而，其治療的應用性則受限於這群細胞的來源稀少，並且內皮前驅細胞之數量及功能更會因年紀或心血管疾病之影響而減少。本實驗探討一已熟知且被普遍使用的人胚成骨細胞株hFOB 1.19作為內皮前驅細胞來源之可能性。實驗結果顯示，透過基質膠的培養，hfoB可形成如血管狀的網狀構造，並開始表現內皮細胞的表面標誌蛋白如CD31、Flk-1、CD144及vWF；在該結構底下，hFOB也具有攝入低密度脂蛋白的能力。證實hFOB的確具有分化成內皮細胞的能力；在雞胚絨毛尿囊膜實驗中，hFOB細胞亦展現增進血管增生的能力。這些結果顯示hFOB細胞具有易於取得，而且具一致性之優點，並可以作為未來研究內皮前驅細胞的模型。

The term “Endothelial Progenitor Cell (EPC)” is generally used to describe a cell type that are capable to differentiate into mature endothelial cell and contribute to neo-vascularization in embryo or in ischemic tissues. There have been an increasing number of studies on the role of EPCs as a potential therapeutics agent for vascular disorders. However, the low amounts of EPCs restrict their usefulness, and the number and function of EPCs can be further reduced by age and cardiovascular risk factors. In this study, we hypothesized that a well-studied and commercially available clonal human osteoprogenitor cell line, the fetal osteoblastic 1.19 cell line (hFOB), may have endothelial differentiation potential. We found that hFOB cells are able to differentiate into a tubular network structure and uptake low-density lipoprotein when they are cultured under Matrigel environment. After tube forming, hFOB cells also express the endothelial progenitor cell markers, such as CD31, Flk-1, V-CAM, vWF. Moreover, hFOB cells also increase the vessel number in the chick chorioallantoic membrane ex vivo angiogenesis experiment. Our data suggest that hFOB cells provide for researchers an easily available, homogeneous, and consistent in vitro model for study of human endothelial progenitor cells.

1. Asahara, T., & Isner, J. M. (2002). Endothelial progenitor cells for vascular regeneration. J Hematother Stem Cell Res, 11(2), 171-178.
2. Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., et al. (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science, 275(5302), 964-967.
3. Assmus, B., Schachinger, V., Teupe, C., Britten, M., Lehmann, R., Dobert, N., et al. (2002). Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation, 106(24), 3009-3017.
4. Chang, C., Yen, M. L., Chen, Y. C., Chien, C. C., Huang, H. I., Bai, C., et al. (2006). Placenta-derived multipotent cells exhibit immunosuppressive properties that are enhanced in the presence of interferon-gamma. Stem Cells, 24(11), 2466-2477.
5. Fadini, G. P., de Kreutzenberg, S. V., Coracina, A., Baesso, I., Agostini, C., Tiengo, A., et al. (2006). Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk. Eur Heart J, 27(18), 2247-2255.
6. Ferrari, G., Cusella-De Angelis, G., Coletta, M., Paolucci, E., Stornaiuolo, A., Cossu, G., et al. (1998). Muscle regeneration by bone marrow-derived myogenic progenitors. Science, 279(5356), 1528-1530.
7. Harris, S. A., Enger, R. J., Riggs, B. L., & Spelsberg, T. C. (1995). Development and characterization of a conditionally immortalized human fetal osteoblastic cell line. J Bone Miner Res, 10(2), 178-186.
8. Hayflick, L., & Moorhead, P. S. (1961). The serial cultivation of human diploid cell strains. Exp Cell Res, 25, 585-621.
9. Hofmann, A., Ritz, U., Verrier, S., Eglin, D., Alini, M., Fuchs, S., et al. (2008). The effect of human osteoblasts on proliferation and neo-vessel formation of human umbilical vein endothelial cells in a long-term 3D co-culture on polyurethane scaffolds. Biomaterials, 29(31), 4217-4226.
10. Iwaguro, H., Yamaguchi, J., Kalka, C., Murasawa, S., Masuda, H., Hayashi, S., et al. (2002). Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation, 105(6), 732-738.
11. Kalka, C., Masuda, H., Takahashi, T., Kalka-Moll, W. M., Silver, M., Kearney, M., et al. (2000). Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A, 97(7), 3422-3427.
12. Kondo, T., Hayashi, M., Takeshita, K., Numaguchi, Y., Kobayashi, K., Iino, S., et al. (2004). Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers. Arterioscler Thromb Vasc Biol, 24(8), 1442-1447.
13. Kopen, G. C., Prockop, D. J., & Phinney, D. G. (1999). Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci U S A, 96(19), 10711-10716.
14. Murasawa, S., Llevadot, J., Silver, M., Isner, J. M., Losordo, D. W., & Asahara, T. (2002). Constitutive human telomerase reverse transcriptase expression enhances regenerative properties of endothelial progenitor cells. Circulation, 106(9), 1133-1139.
15. Naruse, K., & Nakamura, J. (2005). [Therapeutic vasculogenesis using endothelial progenitor cells for treatment of diabetic neuropathies]. Nippon Rinsho, 63 Suppl 6, 622-626.
16. Patan, S., Haenni, B., & Burri, P. H. (1993). Evidence for intussusceptive capillary growth in the chicken chorio-allantoic membrane (CAM). Anat Embryol (Berl), 187(2), 121-130.
17. Peichev, M., Naiyer, A. J., Pereira, D., Zhu, Z., Lane, W. J., Williams, M., et al. (2000). Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood, 95(3), 952-958.
18. Perutelli, P., & Mori, P. G. (1997). Interaction of the von Willebrand factor with platelets and thrombosis. Recenti Prog Med, 88(11), 526-529.
19. Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284(5411), 143-147.
20. Planat-Benard, V., Silvestre, J. S., Cousin, B., Andre, M., Nibbelink, M., Tamarat, R., et al. (2004). Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation, 109(5), 656-663.
21. Rafii, S., & Lyden, D. (2003). Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med, 9(6), 702-712.
22. Reyes, M., Dudek, A., Jahagirdar, B., Koodie, L., Marker, P. H., & Verfaillie, C. M. (2002). Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest, 109(3), 337-346.
23. Reyes, M., Lund, T., Lenvik, T., Aguiar, D., Koodie, L., & Verfaillie, C. M. (2001). Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood, 98(9), 2615-2625.
24. Ribatti, D., Vacca, A., Nico, B., Ria, R., & Dammacco, F. (2002). Cross-talk between hematopoiesis and angiogenesis signaling pathways. Curr Mol Med, 2(6), 537-543.
25. Risau, W., & Flamme, I. (1995). Vasculogenesis. Annu Rev Cell Dev Biol, 11, 73-91.
26. Rouet, V., Hamma-Kourbali, Y., Petit, E., Panagopoulou, P., Katsoris, P., Barritault, D., et al. (2005). A synthetic glycosaminoglycan mimetic binds vascular endothelial growth factor and modulates angiogenesis. J Biol Chem, 280(38), 32792-32800.
27. Semenza, G. L. (2007). Vasculogenesis, angiogenesis, and arteriogenesis: mechanisms of blood vessel formation and remodeling. J Cell Biochem, 102(4), 840-847.
28. Subramaniam, M., Jalal, S. M., Rickard, D. J., Harris, S. A., Bolander, M. E., & Spelsberg, T. C. (2002). Further characterization of human fetal osteoblastic hFOB 1.19 and hFOB/ER alpha cells: bone formation in vivo and karyotype analysis using multicolor fluorescent in situ hybridization. J Cell Biochem, 87(1), 9-15.
29. Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663-676.
30. Tepper, O. M., Galiano, R. D., Capla, J. M., Kalka, C., Gagne, P. J., Jacobowitz, G. R., et al. (2002). Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation, 106(22), 2781-2786.
31. Vasa, M., Fichtlscherer, S., Aicher, A., Adler, K., Urbich, C., Martin, H., et al. (2001). Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res, 89(1), E1-7.
32. Wu, C. C., Chao, Y. C., Chen, C. N., Chien, S., Chen, Y. C., Chien, C. C., et al. (2008). Synergism of biochemical and mechanical stimuli in the differentiation of human placenta-derived multipotent cells into endothelial cells. Journal of Biomechanics, 41(4), 813-821.
33. Yamamoto, K., Takahashi, T., Asahara, T., Ohura, N., Sokabe, T., Kamiya, A., et al. (2003). Proliferation, differentiation, and tube formation by endothelial progenitor cells in response to shear stress. J Appl Physiol, 95(5), 2081-2088.
34. Yang, S., Graham, J., Kahn, J. W., Schwartz, E. A., & Gerritsen, M. E. (1999). Functional roles for PECAM-1 (CD31) and VE-cadherin (CD144) in tube assembly and lumen formation in three-dimensional collagen gels. Am J Pathol, 155(3), 887-895.
35. Yen, B. L., Huang, H. I., Chien, C. C., Jui, H. Y., Ko, B. S., Yao, M., et al. (2005). Isolation of multipotent cells from human term placenta. Stem Cells, 23(1), 3-9.
36. Yen, M. L., Chien, C. C., Chiu, I., Huang, H. I., Chen, Y. C., Hu, H., et al. (2007). Multilineage Differentiation and Characterization of the Human Fetal Osteoblastic 1.19 Cell Line: A Possible In Vitro Model of Human Mesenchymal Progenitors. Stem Cells, 25(1), 125-131.
37. Zengin, E., Chalajour, F., Gehling, U. M., Ito, W. D., Treede, H., Lauke, H., et al. (2006). Vascular wall resident progenitor cells: a source for postnatal vasculogenesis. Development, 133(8), 1543-1551.