Abstract
A fiber-modified adenovirus (rAd5F11B), loaded with the Kringle1-5 gene (rAd-K1-5) was used to infect human adipose tissue-derived mesenchymal stem cells (HAMSCs). At a multiplicity of infection of 20, the transfection efficiency in HAMSCs was 90% and the cell expansion and differentiation of infected HAMSCs were not significantly suppressed. HAMSCs infected with rAd-K1-5 expressed the exogenous Kringle1-5 protein, an angiogenic inhibitor, and conditioned media from HAMSCs expressing the Kringle1-5 protein blocked VEGF-induced neovascularization both in vitro and in vivo. rAd5F11B may therefore be a promising gene transfer vector in HAMSCs-based anti-angiogenic gene therapy because of its low toxicity and high transfection efficiency.
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References
Cao Y, Ji RW et al (1996) Kringle domains of human angiostatin. Characterization of the anti-proliferative activity on endothelial cells. J Biol Chem 271:29461–29467
Cao R, Wu HL et al (1999) Suppression of angiogenesis, tumor growth by the inhibitor K1-5 generated by plasmin-mediated proteolysis. Proc Natl Acad Sci USA 96:5728–5733
De Palma M, Venneri MA, Roca C, Naldini L (2003) Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells. Nat Med 9:789–795
Kern S, Eichler H, Stoeve J, Klüter H, Bieback K (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24:1294–1301
Knaän-Shanzer S, van de Watering MJ et al (2005) Endowing human adenovirus serotype 5 vectors with fiber domains of species B greatly enhances gene transfer into human mesenchymal stem cells. Stem Cells 23:1598–1607
Lin R, Liu J, Gan W, Yang G (2004) C-reactive protein-induced expression of CD40-CD40L and the effect of lovastatin and fenofibrate on it in human vascular endothelial cells. Biol Pharm Bull 27:1537–1543
Lu F, Li J et al (2009) Improvement of the survival of human autologous fat transplantation by using VEGF-transfected adipose-derived stem cells. Plast Reconstr Surg 124:1437–1446
Planat-Benard V, Silvestre JS et al (2004) Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation 109:656–663
Torimura T, Ueno T, Sata M (2006) Liposome-mediated gene transfer of K1-5 suppresses tumor development and improves the prognosis of hepatocellular carcinoma in mice. Med Mol Morphol 39:72–78
Tuve S, Wang H et al (2006) A new group B adenovirus receptor is expressed at high levels on human stem and tumor cells. J Virol 80:12109–12120
Veitonmäki N, Cao R et al (2004) Endothelial cell surface ATP synthase-triggered caspase-apoptotic pathway is essential for k1-5-induced antiangiogenesis. Cancer Res 64:3679–3686
Yotnda P, Onishi H et al (2001) Efficient infection of primitive hematopoietic stem cells by modified adenovirus. Gene Ther 8:930–937
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This work was supported by a grant from the Key Program (No. GB07C32301) from the Heilongjiang Provincial Science and Technology Committee, China.
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H. Liu and Y. Chu contributed equally to this work.
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Liu, H., Chu, Y. & Lou, G. Fiber-modified adenovirus can mediate human adipose tissue-derived mesenchymal stem cell-based anti-angiogenic gene therapy. Biotechnol Lett 32, 1181–1188 (2010). https://doi.org/10.1007/s10529-010-0276-y
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DOI: https://doi.org/10.1007/s10529-010-0276-y