Top

Published in:

01-05-2009 | Experimental

Magnetic targeting of iron-oxide-labeled fluorescent hepatoma cells to the liver

Authors: Alain Luciani, Claire Wilhelm, Patrick Bruneval, Patrick Cunin, Gwennhael Autret, Alain Rahmouni, Olivier Clément, Florence Gazeau

Published in: European Radiology | Issue 5/2009

Abstract

The purpose of this study was to determine whether an external magnet field can induce preferential trafficking of magnetically labeled Huh7 hepatoma cells to the liver following liver cell transplantation. Huh7 hepatoma cells were labeled with anionic magnetic nanoparticles (AMNP) and tagged with a fluorescent membrane marker (PKH67). Iron-uptake was measured by magnetophoresis. Twenty C57Bl6 mice received an intrasplenic injection of 2 × 10⁶ labeled cells. An external magnet (0.29 T; 25 T/m) was placed over the liver of 13 randomly selected animals (magnet group), while the remaining 7 animals served as controls. MRI (1.5 T) and confocal fluorescence microscopy (CFM) were performed 10 days post-transplantation. The presence and location of labeled cells within the livers were compared in the magnet group and controls, and confronted with histological analysis representing the standard of reference. Mean iron content per cell was 6 pg. Based on histology, labeled cells were more frequently present within recipient livers in the magnet group (p < 0.01) where their distribution was preferentially peri-vascular (p < 0.05). MRI and CFM gave similar results for the overall detection of transplanted cells (kappa = 0.828) and for the identification of peri-vascular cells (kappa = 0.78). Application of an external magnet can modify the trafficking of transplanted cells, especially by promoting the formation of perivascular aggregates.

Bulte JW, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17:484–499PubMedCrossRef

Corot C, Robert P, Idee JM, Port M (2006) Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliv Rev 58:1471–1504PubMedCrossRef

Hoehn M, Kustermann E, Blunk J, Wiedermann D, Trapp T, Wecker S, Focking M, Arnold H, Hescheler J, Fleischmann BK, Schwindt W, Buhrle C (2002) Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat. Proc Natl Acad Sci USA 99:16267–16272PubMedCrossRef

Arbab AS, Liu W, Frank JA (2006) Cellular magnetic resonance imaging: current status and future prospects. Expert Rev Med Devices 3:427–439PubMedCrossRef

Pamme N, Wilhelm C (2006) Continuous sorting of magnetic cells via on-chip free-flow magnetophoresis. Lab Chip 6:974–980PubMedCrossRef

Ito A, Hibino E, Kobayashi C, Terasaki H, Kagami H, Ueda M, Kobayashi T, Honda H (2005) Construction and delivery of tissue-engineered human retinal pigment epithelial cell sheets, using magnetite nanoparticles and magnetic force. Tissue Eng 11:489–496PubMedCrossRef

Pislaru SV, Harbuzariu A, Agarwal G, Witt T, Gulati R, Sandhu NP, Mueske C, Kalra M, Simari RD, Sandhu GS (2006) Magnetic forces enable rapid endothelialization of synthetic vascular grafts. Circulation 114:I314–I318PubMedCrossRef

Wilhelm C, Bal L, Smirnov P, Galy-Fauroux I, Clement O, Gazeau F, Emmerich J (2007) Magnetic control of vascular network formation with magnetically labeled endothelial progenitor cells. Biomaterials 28:3797–3806PubMedCrossRef

Wilhelm C, Riviere C, Biais N (2007) Magnetic control of Dictyostelium aggregation. Phys Rev E Stat Nonlin Soft Matter Phys 75:041906PubMed

10.

Ino K, Ito A, Honda H (2007) Cell patterning using magnetite nanoparticles and magnetic force. Biotechnol Bioeng 97:1309–1317PubMedCrossRef

11.

Selden C, Hodgson H (2004) Cellular therapies for liver replacement. Transpl Immunol 12:273–288PubMedCrossRef

12.

Raschzok N, Morgul MH, Pinkernelle J, Vondran FW, Billecke N, Kammer NN, Pless G, Adonopoulou MK, Leist C, Stelter L, Teichgraber U, Schwartlander R, Sauer IM (2008) Imaging of primary human hepatocytes performed with micron-sized iron oxide particles and clinical magnetic resonance tomography. J Cell Mol Med 12:1384–1394PubMedCrossRef

13.

Luciani A, Parouchev A, Smirnov P, Braga G, Wilhelm C, Gazeau F, Boudechiche L, L’Hermine-Coulomb A, Dagher I, Franco D, Rahmouni A, Hadchouel M, Weber A, Clement O (2008) In vivo imaging of transplanted hepatocytes with a 1.5-T clinical MRI system-initial experience in mice. Eur Radiol 18:59–69PubMedCrossRef

14.

Arbab AS, Jordan EK, Wilson LB, Yocum GT, Lewis BK, Frank JA (2004) In vivo trafficking and targeted delivery of magnetically labeled stem cells. Hum Gene Ther 15:351–360PubMedCrossRef

15.

Pislaru SV, Harbuzariu A, Gulati R, Witt T, Sandhu NP, Simari RD, Sandhu GS (2006) Magnetically targeted endothelial cell localization in stented vessels. J Am Coll Cardiol 48:1839–1845PubMedCrossRef

16.

Polyak B, Fishbein I, Chorny M, Alferiev I, Williams D, Yellen B, Friedman G, Levy RJ (2008) High field gradient targeting of magnetic nanoparticle-loaded endothelial cells to the surfaces of steel stents. Proc Natl Acad Sci USA 105:698–703PubMedCrossRef

17.

Lubbe AS, Alexiou C, Bergemann C (2001) Clinical applications of magnetic drug targeting. J Surg Res 95:200–206PubMedCrossRef

18.

Alexiou C, Jurgons R, Schmid RJ, Bergemann C, Henke J, Erhardt W, Huenges E, Parak F (2003) Magnetic drug targeting-biodistribution of the magnetic carrier and the chemotherapeutic agent mitoxantrone after locoregional cancer treatment. J Drug Target 11:139–149PubMedCrossRef

19.

Fortin-Ripoche JP, Martina MS, Gazeau F, Menager C, Wilhelm C, Bacri JC, Lesieur S, Clement O (2006) Magnetic targeting of magnetoliposomes to solid tumors with MR imaging monitoring in mice: feasibility. Radiology 239:415–424PubMedCrossRef

20.

Riviere C, Martina MS, Tomita Y, Wilhelm C, Tran Dinh A, Menager C, Pinard E, Lesieur S, Gazeau F, Seylaz J (2007) Magnetic targeting of nanometric magnetic fluid loaded liposomes to specific brain intravascular areas: a dynamic imaging study in mice. Radiology 244:439–448PubMedCrossRef

21.

Martina MS, Fortin JP, Fournier L, Menager C, Gazeau F, Clement O, Lesieur S (2007) Magnetic targeting of rhodamine-labeled superparamagnetic liposomes to solid tumors: in vivo tracking by fibered confocal fluorescence microscopy. Mol Imaging 6:140–146PubMed

22.

Riviere C, Boudghene FP, Gazeau F, Roger J, Pons JN, Laissy JP, Allaire E, Michel JB, Letourneur D, Deux JF (2005) Iron oxide nanoparticle-labeled rat smooth muscle cells: cardiac MR imaging for cell graft monitoring and quantitation. Radiology 235:959–967PubMedCrossRef

23.

Smirnov P, Lavergne E, Gazeau F, Lewin M, Boissonnas A, Doan BT, Gillet B, Combadiere C, Combadiere B, Clement O (2006) In vivo cellular imaging of lymphocyte trafficking by MRI: A tumor model approach to cell-based anticancer therapy. Magn Reson Med 56:498–508PubMedCrossRef

24.

Billotey C, Wilhelm C, Devaud M, Bacri JC, Bittoun J, Gazeau F (2003) Cell internalization of anionic maghemite nanoparticles: quantitative effect on magnetic resonance imaging. Magn Reson Med 49:646–654PubMedCrossRef

25.

Wilhelm C, Gazeau F, Bacri JC (2002) Magnetophoresis and ferromagnetic resonance of magnetically labeled cells. Eur Biophys J 31:118–125PubMedCrossRef

26.

Teare GF, Horan PK, Slezak SE, Smith C, Hay JB (1991) Long-term tracking of lymphocytes in vivo: the migration of PKH-labeled lymphocytes. Cell Immunol 134:157–170PubMedCrossRef

27.

Laemmel E, Genet M, Le Goualher G, Perchant A, Le Gargasson JF, Vicaut E (2004) Fibered confocal fluorescence microscopy (Cell-viZio) facilitates extended imaging in the field of microcirculation. A comparison with intravital microscopy. J Vasc Res 41:400–411PubMedCrossRef

28.

D’Hallewin MA, El Khatib S, Leroux A, Bezdetnaya L, Guillemin F (2005) Endoscopic confocal fluorescence microscopy of normal and tumor bearing rat bladder. J Urol 174:736–740PubMedCrossRef

29.

Pelled G, Dodd SJ, Koretsky AP (2006) Catheter confocal fluorescence imaging and functional magnetic resonance imaging of local and systems level recovery in the regenerating rodent sciatic nerve. Neuroimage 30:847–856PubMedCrossRef

30.

Allen KJ, Cheah DM, Wright PF, Gazeas S, Pettigrew-Buck NE, Deal YH, Mercer JF, Williamson R (2004) Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson’s disease. J Gastroenterol Hepatol 19:1283–1290PubMedCrossRef

31.

Heyn C, Bowen CV, Rutt BK, Foster PJ (2005) Detection threshold of single SPIO-labeled cells with FIESTA. Magn Reson Med 53:312–320PubMedCrossRef

32.

Shapiro EM, Skrtic S, Sharer K, Hill JM, Dunbar CE, Koretsky AP (2004) MRI detection of single particles for cellular imaging. Proc Natl Acad Sci USA 101:10901–10906PubMedCrossRef

33.

Shapiro EM, Sharer K, Skrtic S, Koretsky AP (2006) In vivo detection of single cells by MRI. Magn Reson Med 55:242–249PubMedCrossRef

34.

Widder KJ, Morris RM, Poore G, Howard DP Jr, Senyei AE (1981) Tumor remission in Yoshida sarcoma-bearing rts by selective targeting of magnetic albumin microspheres containing doxorubicin. Proc Natl Acad Sci USA 78:579–581PubMedCrossRef

35.

Lubbe AS, Bergemann C, Riess H, Schriever F, Reichardt P, Possinger K, Matthias M, Dorken B, Herrmann F, Gurtler R, Hohenberger P, Haas N, Sohr R, Sander B, Lemke AJ, Ohlendorf D, Huhnt W, Huhn D (1996) Clinical experiences with magnetic drug targeting: a phase I study with 4′-epidoxorubicin in 14 patients with advanced solid tumors. Cancer Res 56:4686–4693PubMed

36.

Lemke AJ, Senfft von Pilsach MI, Lubbe A, Bergemann C, Riess H, Felix R (2004) MRI after magnetic drug targeting in patients with advanced solid malignant tumors. Eur Radiol 14:1949–1955PubMedCrossRef

Title: Magnetic targeting of iron-oxide-labeled fluorescent hepatoma cells to the liver
Authors: Alain Luciani
Claire Wilhelm
Patrick Bruneval
Patrick Cunin
Gwennhael Autret
Alain Rahmouni
Olivier Clément
Florence Gazeau
Publication date: 01-05-2009
Publisher: Springer-Verlag
Published in: European Radiology / Issue 5/2009
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-008-1262-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Magnetic targeting of iron-oxide-labeled fluorescent hepatoma cells to the liver

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2009

Contrast-enhanced magnetic resonance angiography in carotid artery disease: does automated image registration improve image quality?

Kinematic biomechanical assessment of human articular cartilage transplants in the knee using 3-T MRI: an in vivo reproducibility study

Dose reduction in computed tomography: the effect of eye and testicle shielding on radiation dose measured in patients with beryllium oxide-based optically stimulated luminescence dosimetry

Dual-energy CT iodine overlay technique for characterization of renal masses as cyst or solid: a phantom feasibility study

Variability of bronchial measurements obtained by sequential CT using two computer-based methods

A rare cause of pulmonary embolism (2009: 5a)