In Vitro Evaluation of Magnetic Resonance Imaging Contrast Agents for Labeling Human Liver Cells: Implications for Clinical Translation

Overview

Journal Mol Imaging Biol

Publisher Springer

Specialties Molecular Biology
Radiology

Date 2010 Aug 26

PMID 20737221

Citations 6

Authors

Nathanael Raschzok

David A Muecke

Michaela K Adonopoulou

Nils Billecke

Wiebke Werner

Nora N Kammer

Anja Zielinski

Peter A Behringer

Frauke Ringel

Mao D Huang

Peter Neuhaus

Ulf Teichgraber

Igor M Sauer

Affiliations

Soon will be listed here.

Abstract

Purpose: Magnetic resonance imaging (MRI) is a promising approach for non-invasive monitoring after liver cell transplantation. We compared in vitro labeling of human liver cells with nano-sized (SPIO) and micron-sized iron oxide particles (MPIO).

Procedures: The cellular iron load was quantified and phantom studies were performed using 3.0-T MRI. Transferrin receptor and ferritin gene expression, reactive oxygen species (ROS) formation, transaminase leakage, and urea synthesis were investigated over 6 days.

Results: Incubation with MPIO produced stronger signal extinctions in MRI at similar iron loads within shorter labeling time. MPIO had no negative effects on the cellular iron homeostasis or cell performance, whereas SPIO caused temporary ROS formation and non-physiologic activation of the iron metabolic pathway.

Conclusions: Our findings suggest that MPIO are suited for clinical translation of strategies for cellular imaging with MRI. Attention should be paid to iron release and oxidative stress caused by biodegradable contrast agents.

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References

Strom S, Chowdhury J, Fox I . Hepatocyte transplantation for the treatment of human disease. Semin Liver Dis. 1999; 19(1):39-48. DOI: 10.1055/s-2007-1007096. View

Wang L, Deng J, Wang J, Xiang B, Yang T, Gruwel M . Superparamagnetic iron oxide does not affect the viability and function of adipose-derived stem cells, and superparamagnetic iron oxide-enhanced magnetic resonance imaging identifies viable cells. Magn Reson Imaging. 2008; 27(1):108-19. DOI: 10.1016/j.mri.2008.05.013. View

Hussain S, Raja K, Amstad P, Sawyer M, Trudel L, Wogan G . Increased p53 mutation load in nontumorous human liver of wilson disease and hemochromatosis: oxyradical overload diseases. Proc Natl Acad Sci U S A. 2000; 97(23):12770-5. PMC: 18839. DOI: 10.1073/pnas.220416097. View

Slotkin J, Cahill K, Tharin S, Shapiro E . Cellular magnetic resonance imaging: nanometer and micrometer size particles for noninvasive cell localization. Neurotherapeutics. 2007; 4(3):428-33. PMC: 7479728. DOI: 10.1016/j.nurt.2007.05.010. View

Tong X, Kawabata H, Koeffler H . Iron deficiency can upregulate expression of transferrin receptor at both the mRNA and protein level. Br J Haematol. 2002; 116(2):458-64. View

Gu J, Lim S, Oh S, Yoon S, Seong J, Jung G . HBx modulates iron regulatory protein 1-mediated iron metabolism via reactive oxygen species. Virus Res. 2008; 133(2):167-77. DOI: 10.1016/j.virusres.2007.12.014. View

Pawelczyk E, Arbab A, Pandit S, Hu E, Frank J . Expression of transferrin receptor and ferritin following ferumoxides-protamine sulfate labeling of cells: implications for cellular magnetic resonance imaging. NMR Biomed. 2006; 19(5):581-92. DOI: 10.1002/nbm.1038. View

Puppi J, Modo M . Use of magnetic resonance imaging contrast agents to detect transplanted liver cells. Top Magn Reson Imaging. 2009; 20(2):113-20. DOI: 10.1097/RMR.0b013e3181c0dfe4. View

Hubert N, Lescoat G, Sciot R, Moirand R, Jego P, Leroyer P . Regulation of ferritin and transferrin receptor expression by iron in human hepatocyte cultures. J Hepatol. 1993; 18(3):301-12. DOI: 10.1016/s0168-8278(05)80274-0. View

10.

Schafer R, Kehlbach R, Muller M, Bantleon R, Kluba T, Ayturan M . Labeling of human mesenchymal stromal cells with superparamagnetic iron oxide leads to a decrease in migration capacity and colony formation ability. Cytotherapy. 2009; 11(1):68-78. DOI: 10.1080/14653240802666043. View

11.

Choi D, Kim J, Lim M, Song K, Paik S, Kim S . Hepatocyte-like cells from human mesenchymal stem cells engrafted in regenerating rat liver tracked with in vivo magnetic resonance imaging. Tissue Eng Part C Methods. 2008; 14(1):15-23. DOI: 10.1089/tec.2007.0329. View

12.

Schafer R, Ayturan M, Bantleon R, Kehlbach R, Siegel G, Pintaske J . The use of clinically approved small particles of iron oxide (SPIO) for labeling of mesenchymal stem cells aggravates clinical symptoms in experimental autoimmune encephalomyelitis and influences their in vivo distribution. Cell Transplant. 2008; 17(8):923-41. DOI: 10.3727/096368908786576480. View

13.

Crabbe A, Vandeputte C, Dresselaers T, Ayuso Sacido A, Garcia Verdugo J, Eyckmans J . Effects of MRI contrast agents on the stem cell phenotype. Cell Transplant. 2010; 19(8):919-36. DOI: 10.3727/096368910X494623. View

14.

Modo M . Noninvasive imaging of transplanted cells. Curr Opin Organ Transplant. 2008; 13(6):654-8. DOI: 10.1097/MOT.0b013e328317a43c. View

15.

Dhawan A, Mitry R, Hughes R, Lehec S, Terry C, Bansal S . Hepatocyte transplantation for inherited factor VII deficiency. Transplantation. 2004; 78(12):1812-4. DOI: 10.1097/01.tp.0000146386.77076.47. View

16.

Raschzok N, Morgul M, Pinkernelle J, Vondran F, Billecke N, Kammer N . Imaging of primary human hepatocytes performed with micron-sized iron oxide particles and clinical magnetic resonance tomography. J Cell Mol Med. 2008; 12(4):1384-94. PMC: 3865680. DOI: 10.1111/j.1582-4934.2008.00343.x. View

17.

Aisen P, Enns C, Wessling-Resnick M . Chemistry and biology of eukaryotic iron metabolism. Int J Biochem Cell Biol. 2001; 33(10):940-59. DOI: 10.1016/s1357-2725(01)00063-2. View

18.

Luciani A, Parouchev A, Smirnov P, Braga G, Wilhelm C, Gazeau F . In vivo imaging of transplanted hepatocytes with a 1.5-T clinical MRI system--initial experience in mice. Eur Radiol. 2007; 18(1):59-69. PMC: 5336554. DOI: 10.1007/s00330-007-0750-7. View

19.

Andriopoulos B, Hegedusch S, Mangin J, Riedel H, Hebling U, Wang J . Sustained hydrogen peroxide induces iron uptake by transferrin receptor-1 independent of the iron regulatory protein/iron-responsive element network. J Biol Chem. 2007; 282(28):20301-8. DOI: 10.1074/jbc.M702463200. View

20.

Ju S, Teng G, Lu H, Zhang Y, Zhang A, Chen F . In vivo MR tracking of mesenchymal stem cells in rat liver after intrasplenic transplantation. Radiology. 2007; 245(1):206-15. DOI: 10.1148/radiol.2443061290. View