Optical Imaging of the Adoptive Transfer of Human Endothelial Cells in Mice Using Anti-Human CD31 Monoclonal Antibody
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
The development of endothelium-specific imaging agents capable of specific binding to human cells under the conditions of flow for the needs of regenerative medicine and cancer research. The goal of the study was testing the feasibility of optical imaging of human endothelial cells implanted in mice.
Mouse model of adoptive human endothelial cell transfer was obtained by implanting cells in Matrigel matrix in subcutaneous space (Kang, Torres, Wald, Weissleder, and Bogdanov, Jr., Targeted imaging of human endothelial-specific marker in a model of adoptive cell transfer. Lab. Invest. 86: 599-609, 2006). Several endothelium-specific proteins were labeled with near-infrared fluorochrome (Cy5.5) and tested in vitro. Fluorescence imaging using anti-human CD31 antibody was performed in vivo. The obtained results were corroborated by using fluorescence microscopy of tissue sections.
We determined that monoclonal anti-human CD31 antibodies labeled with Cy5.5 were efficiently binding to human endothelial cells and were not subject to rapid endocytosis.We further demonstrated that specific near-infrared optical imaging signal was present only in Matrigel implants seeded with human endothelium cells and was absent from control Matrigel implants. Histology showed staining of cells lining vessels and revealed the formation of branched networks of CD31-positive cells.
Anti-human CD31 antibodies tagged with near-infrared fluorochromes can be used for detection of perfused blood vessels harboring human endothelial cells in animal models of adoptive transfer.
- H. W. Kang, D. Torres, L. Wald, R. Weissleder, and A. A. Bogdanov, Jr. Targeted imaging of human endothelial-specific marker in a model of adoptive cell transfer. Lab. Invest. 86:599–609 (2006).
- A. L. Klibanov. Microbubble contrast agents: targeted ultrasound imaging and ultrasound-assisted drug-delivery applications. Invest. Radiol. 41:354–362 (2006). CrossRef
- F. G. Blankenberg, C. Mari, and H. W. Strauss. Development of radiocontrast agents for vascular imaging: progress to date. Am. J. Cardiovasc. Drugs 2:357–365 (2002). CrossRef
- X. Chen, M. Tohme, R. Park, Y. Hou, J. R. Bading, and P. S. Conti. Micro-PET imaging of alphavbeta3-integrin expression with 18F-labeled dimeric RGD peptide. Mol. Imag. 3:96–104 (2004). CrossRef
- H. Leong-Poi, J. Christiansen, A. L. Klibanov, S. Kaul, and J. R. Lindner. Noninvasive assessment of angiogenesis by ultrasound and microbubbles targeted to alpha(v)-integrins. Circulation 107:455–60 (2003). CrossRef
- M. M. Sadeghi, J. S. Schechner, S. Krassilnikova, A. A. Gharaei, J. Zhang, N. Kirkiles-Smith, A. J. Sinusas, B. L. Zaret, and J. R. Bender. Vascular cell adhesion molecule-1-targeted detection of endothelial activation in human microvasculature. Transplant. Proc. 36:1585–91 (2004). CrossRef
- K. A. Kelly, J. R. Allport, A. Tsourkas, V. R. Shinde-Patil, L. Josephson, and R. Weissleder. Detection of vascular adhesion molecule-1 expression using a novel multimodal nanoparticle. Circ. Res. 96:327–336 (2005). CrossRef
- S. Boutry, C. Burtea, S. Laurent, G. Toubeau, L. Vander Elst, and R. N. Muller. Magnetic resonance imaging of inflammation with a specific selectin-targeted contrast agent. Magn. Reson. Med. 53:800–807 (2005). CrossRef
- P. Valadon, J. D. Garnett, J. E. Testa, M. Bauerle, P. Oh, and J. E. Schnitzer. Screening phage display libraries for organ-specific vascular immunotargeting in vivo. Proc. Natl. Acad. Sci. USA 103:407–12 (2006). CrossRef
- E. R. Horak, R. Leek, N. Klenk, S. LeJeune, K. Smith, N. Stuart, M. Greenall, K. Stepniewska, and A. L. Harris. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet 340:1120–1124 (1992). CrossRef
- S. B. Fox, K. C. Gatter, R. Bicknell, J. J. Going, P. Stanton, T. G. Cooke, and A. L. Harris. Relationship of endothelial cell proliferation to tumor vascularity in human breast cancer. Cancer Res. 53:4161–3 (1993).
- J. M. Runnels, P. Zamiri, J. A. Spencer, I. Veilleux, X. Wei, A. Bogdanov, and C. P. Lin. Imaging molecular expression on vascular endothelial cells by in vivo immunofluorescence microscopy. Mol. Imag. 5:31–40 (2006).
- N. Koike, D. Fukumura, O. Gralla, P. Au, J. S. Schechner, and R. K. Jain. Tissue engineering: creation of long-lasting blood vessels. Nature 428:138–139 (2004). CrossRef
- H. W. Kang, L. Josephson, A. Petrovsky, R. Weissleder, and A. Bogdanov, Jr. Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell culture. Bioconj. Chem. 13:122–127 (2002). CrossRef
- M. T. Nakada, K. Amin, M. Christofidou-Solomidou, C. D. O’Brien, J. Sun, I. Gurubhagavatula, G. A. Heavner, A. H. Taylor, C. Paddock, Q. H. Sun, J. L. Zehnder, P. J. Newman, S. M. Albelda, and H. M. DeLisser. Antibodies against the first Ig-like domain of human platelet endothelial cell adhesion molecule-1 (PECAM-1) that inhibit PECAM-1-dependent homophilic adhesion block in vivo neutrophil recruitment. J. Immunol. 164:452–462 (2000).
- A. Bogdanov, Jr, C. Lin, M. Simonova, L. Matuszewski, and R. Weissleder. Cellular activation of the self-quenched fluorescent reporter probe in tumor microenvironment. Neoplasia 4:228–236 (2002). CrossRef
- T. Troy, D. Jekic-McMullen, L. Sambucetti, and B. Rice. Quantitative comparison of the sensitivity of detection of fluorescent and bioluminescent reporters in animal models. Mol. Imag. 3:19–23 (2004). CrossRef
- J. S. Schechner, A. K. Nath, L. Zheng, M. S. Kluger, C. C. Hughes, M. R. Sierra-Honigmann, M. I. Lorber, G. Tellides, M. Kashgarian, A. L. Bothwell, and J. S. Pober. in vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse. [see comment]. Proc. Natl. Acad. Sci. USA 97:9191–9196 (2000). CrossRef
- D. K. Skovseth, T. Yamanaka, P. Brandtzaeg, E. C. Butcher, and G. Haraldsen. Vascular morphogenesis and differentiation after adoptive transfer of human endothelial cells to immunodeficient mice. Am. J. Pathol. 160:1629–1637 (2002).
- D. R. Enis, B. R. Shepherd, Y. Wang, A. Qasim, C. M. Shanahan, P. L. Weissberg, M. Kashgarian, J. S. Pober, and J. S. Schechner. Induction, differentiation, and remodeling of blood vessels after transplantation of Bcl-2-transduced endothelial cells. Proc. Natl. Acad. Sci. USA 102:425–430 (2005). CrossRef
- D. Hawryszand, and E. Sevick-Muraca. Developments toward diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents. Neoplasia 2:388–417 (2000). CrossRef
- V. Ntziachristos, C. Bremer, and R. Weissleder. Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging. Eur. Radiol. 13:195–208 (2003).
- V. Ntziachristos. Fluorescence molecular imaging. Annu. Rev. Biomed. Eng. 8:1–33 (2006). CrossRef
- K. Lichaand, and C. Olbrich. Optical imaging in drug discovery and diagnostic applications. Adv. Drug Deliv. Rev. 57:1087–1108 (2005). CrossRef
- R. F. Nicosiaand, and A. Ottinetti. Modulation of microvascular growth and morphogenesis by reconstituted basement membrane gel in three-dimensional cultures of rat aorta: a comparative study of angiogenesis in matrigel, collagen, fibrin, and plasma clot. In Vitro Cell. Dev. Biol. 26:119–128 (1990). CrossRef
- A. Passaniti, R. M. Taylor, R. Pili, Y. Guo, P. V. Long, J. A. Haney, R. R. Pauly, D. S. Grant, and G. R. Martin. A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor. Lab. Invest. 67:519–528 (1992).
- A. Petrovsky, E. Schellenberger, L. Josephson, R. Weissleder, and A. Bogdanov, Jr. Near-infrared fluorescent imaging of tumor apoptosis. Cancer Res. 63:1936–1942 (2003).
- D. M. McDonaldand, and P. L. Choyke. Imaging of angiogenesis: from microscope to clinic. Nat Med. 9:713–725 (2003). CrossRef
- H. Holthofer, I. Virtanen, A. L. Kariniemi, M. Hormia, E. Linder, and A. Miettinen. Ulex europaeus I lectin as a marker for vascular endothelium in human tissues. Lab. Invest. 47:60–66 (1982).
- E. J. von Asmuth, E. F. Smeets, L. A. Ginsel, J. J. Onderwater, J. F. Leeuwenberg, and W. A. Buurman. Evidence for endocytosis of E-selectin in human endothelial cells. Eur. J. Immunol. 22:2519–2526 (1992). CrossRef
- P. I. Chuang, B. A. Young, R. R. Thiagarajan, C. Cornejo, R. K. Winn, and J. M. Harlan. Cytoplasmic domain of E-selectin contains a non-tyrosine endocytosis signal. J. Biol. Chem. 272:24813–24818 (1997). CrossRef
- Optical Imaging of the Adoptive Transfer of Human Endothelial Cells in Mice Using Anti-Human CD31 Monoclonal Antibody
Volume 24, Issue 6 , pp 1186-1192
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers-Plenum Publishers
- Additional Links
- adoptive transfer
- molecular imaging
- Industry Sectors
- Author Affiliations
- 1. S2-804, Department of Radiology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, Massachusetts, 01655, USA
- 2. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA