MRI of transplanted pancreatic islets
Corresponding Author
Daniel Jirák
MR-Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Center for Cell Therapy and Tissue Repair, 2nd Medical Faculty, Charles University, Prague, Czech Republic
MR Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Praha 4, Czech Republic===Search for more papers by this authorJan Kríz
Laboratory of Islets of Langerhans, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Search for more papers by this authorVít Herynek
MR-Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Search for more papers by this authorBenita Andersson
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
Department of Neuroscience, Institute of Experimental Medicine ASCR, Prague, Czech Republic
Search for more papers by this authorPeter Girman
Laboratory of Islets of Langerhans, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Search for more papers by this authorMartin Burian
MR-Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Center for Cell Therapy and Tissue Repair, 2nd Medical Faculty, Charles University, Prague, Czech Republic
Search for more papers by this authorFrantišek Saudek
Center for Cell Therapy and Tissue Repair, 2nd Medical Faculty, Charles University, Prague, Czech Republic
Laboratory of Islets of Langerhans, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Search for more papers by this authorMilan Hájek
MR-Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Center for Cell Therapy and Tissue Repair, 2nd Medical Faculty, Charles University, Prague, Czech Republic
Search for more papers by this authorCorresponding Author
Daniel Jirák
MR-Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Center for Cell Therapy and Tissue Repair, 2nd Medical Faculty, Charles University, Prague, Czech Republic
MR Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Praha 4, Czech Republic===Search for more papers by this authorJan Kríz
Laboratory of Islets of Langerhans, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Search for more papers by this authorVít Herynek
MR-Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Search for more papers by this authorBenita Andersson
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
Department of Neuroscience, Institute of Experimental Medicine ASCR, Prague, Czech Republic
Search for more papers by this authorPeter Girman
Laboratory of Islets of Langerhans, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Search for more papers by this authorMartin Burian
MR-Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Center for Cell Therapy and Tissue Repair, 2nd Medical Faculty, Charles University, Prague, Czech Republic
Search for more papers by this authorFrantišek Saudek
Center for Cell Therapy and Tissue Repair, 2nd Medical Faculty, Charles University, Prague, Czech Republic
Laboratory of Islets of Langerhans, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Search for more papers by this authorMilan Hájek
MR-Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Center for Cell Therapy and Tissue Repair, 2nd Medical Faculty, Charles University, Prague, Czech Republic
Search for more papers by this authorAbstract
A promising treatment method for type 1 diabetes mellitus is transplantation of pancreatic islets containing β-cells. The aim of this study was to develop an MR technique to monitor the distribution and fate of transplanted pancreatic islets in an animal model. Twenty-five hundred purified and magnetically labeled islets were transplanted through the portal vein into the liver of experimental rats. The animals were scanned using a MR 4.7-T scanner. The labeled pancreatic islets were clearly visualized in the liver in both diabetic and healthy rats as hypointense areas on T2*-weighted MR images during the entire measurement period. Transmission electron microscopy confirmed the presence of iron-oxide nanoparticles inside the cells of the pancreatic islets. A significant decrease in blood glucose levels in diabetic rats was observed; normal glycemia was reached 1 week after transplantation. This study, therefore, represents a promising step toward possible clinical application in human medicine. Magn Reson Med 52:1228–1233, 2004. © 2004 Wiley-Liss, Inc.
REFERENCES
- 1 White SA, James RFL, Swift SM, Kimber RM, Nicholson ML. Human islet cell transplantation—Future prospects. Diabet Med 2001; 18: 78–103.
- 2 Shapiro AM, Ryan EA, Lakey JRT. Pancreatic islet transplantation in the treatment of diabetes mellitus. Best Pract Res Clin Endocrinol Metab 2001; 15: 241–64.
- 3 Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343: 230–238.
- 4 Vajkoczy P, Olofsson AM, Lehr HA, Leiderer R, Hammersen F, Arfors KE, Menger MD. Histogenesis and ultrastructure of pancreatic islet graft microvasculature. Evidence for graft revascularization by endothelial cells of host origin. Am J Pathol 1995; 146: 1397–1405.
- 5 Bulte JW, Duncan ID, Frank JA. In vivo magnetic resonance tracking of magnetically labeled cells after transplantation. J Cereb Blood Flow Metab 2002; 22: 899–907.
- 6 Jendelova P, Herynek V, DeCroos J, Glogarova K, Andersson B, Hajek M, Sykova E. Imaging the fate of implanted bone marrow stromal cells labeled with superparamagnetic nanoparticles. Magn Reson Med 2003; 50: 767–776.
- 7 Norman AB, Thomas SR, Pratt RG, Lu SY, Norgren RB. Magnetic resonance imaging of neural transplants in rat brain using a superparamagnetic contrast agent Brain Res 1992; 594: 279–283.
- 8 Shen T, Weissleder R, Papisov M, Bogdanov AJ, Brady TJ. Monocrystalline iron oxide nanocompounds (MION): Physicochemical properties. Magn Reson Med 1993; 29: 599–604.
- 9 Bulte JW, Brooks RA, Moskowitz BM, Bryant LHJ, Frank JA. T1 and T2 relaxometry of monocrystalline iron oxide nanoparticles (MION-46L): Theory and experiment. Acad Radiology 1998; 5: S137–S140.
- 10
Bulte JW,
Brooks RA,
Moskowitz BM,
Bryant LHJ,
Frank JA.
Relaxometry and magnetometry of the MR contrast agent MION-46L.
Magn Reson Med
1999;
42:
379–384.
10.1002/(SICI)1522-2594(199908)42:2<379::AID-MRM20>3.0.CO;2-L CAS PubMed Web of Science® Google Scholar
- 11 Hoehn M, Kustermann E, Blunk J, Wiedermann D, Trapp T, Focking M, Arnold H, Hescheler J, Fleischmann BK, Buhrle C. 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 2002; 100: 1073–1078.
- 12 Kalish H, Arbab AS, Miller BR, Lewis BK, Zywicke HA, Bulte JW, Bryant LH Jr., Frank JA. Combination of transfection agents and magnetic resonance contrast agents for cellular imaging: Relationship between relaxivities, electrostatic forces, and chemical composition. Magn Reson Med 2003; 50: 275–282.
- 13 Kaufman CL, Williams M, Ryle LM, Smith TL, Tanner M, Ho C. Superparamagnetic iron oxide particles transactivator protein-fluorescein isothiocyanate particle labelling for in vivo magnetic resonance imaging detection of cell migration: Uptake and durability. Transplantation 2003; 76: 1043–1046.
- 14 Moore A, Sun PZ, Cory D, Hogemann D, Weissleder R, Lipes MA. MRI of insulitis in autoimmune diabetes Magn Reson Med 2002; 47: 751–758.
- 15 Hinds KA, Hill JM, Shapiro EM, Laukkanen MO, Silva AC, Combs CA, Varney TR, Balaban RS, Koretsky AP, Dunbar CE. Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells. Blood 2003; 102: 867–872.
- 16 Lacy PE, Kostianovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 1967; 16: 35–39.
- 17 Saudek F, Cihalova E, Karasova L, Kobylka P, Lomsky R. Increased glucagon-stimulated insulin secretion of cryopreserved rat islets transplanted into nude mice. J Mol Med 1999; 77: 107–110.
- 18 Wang YX, Hussain SM, Krestin GP. Superparamagnetic iron oxide contrast agents: Physicochemical characteristics and applications in MR imaging. Eur Radiology 2001; 11: 2319–2331.
- 19 Reimer P, Balzer T. Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: Properties, clinical development, and applications. Eur Radiology 2003; 13: 1266–1276.
- 20 Giannarelli R, Coppelli A, Marchetti P, Tellini C, Del Guerra S, Lupi R, Lorenzetti M, Masiello P, Carmellini M, Mosca F, Lencioni C, Navalesi R. Preparation and long-term culture of isolated human pancreatic islets. Transplant Proc 1998; 30: 384–385.
- 21 Markmann JF, Rosen M, Siegelman ES, Soulen MC, Deng S, Barker CF, Naji A. Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: A functional footprint of islet graft survival? Diabetes 2003; 52: 1591–1594.
- 22 Hadjivassiliou V, Green MH, Green IC. Immunomagnetic purification of beta cells from rat islets of Langerhans. Diabetologia 2000; 43: 1170–1177.
