title: Magnetic resonance imaging of mouse islet grafts labeled with novel chitosan-coated superparamagnetic iron oxide nanoparticles.
abstract: OBJECTIVE
  To better understand the fate of islet isografts and allografts, we utilized a magnetic resonance (MR) imaging technique to monitor mouse islets labeled with a novel MR contrast agent, chitosan-coated superparamagnetic iron oxide (CSPIO) nanoparticles.
  
  
  METHODS
  After being incubated with and without CSPIO (10 µg/ml), C57BL/6 mouse islets were examined under transmission electron microscope (TEM) and their insulin secretion was measured. Cytotoxicity was examined in α (αTC1) and β (NIT-1 and βTC) cell lines as well as islets. C57BL/6 mice were used as donors and inbred C57BL/6 and Balb/c mice were used as recipients of islet transplantation. Three hundred islets were transplanted under the left kidney capsule of each mouse and then MR was performed in the recipients periodically. At the end of study, the islet graft was removed for histology and TEM studies.
  
  
  RESULTS
  After incubation of mouse islets with CSPIO (10 µg/mL), TEM showed CSPIO in endocytotic vesicles of α- and β-cells at 8 h. Incubation with CSPIO did not affect insulin secretion from islets and death rates of αTC1, NIT-1 and βTC cell lines as well as islets. After syngeneic and allogeneic transplantation, grafts of CSPIO-labeled islets were visualized on MR scans as persistent hypointense areas. At 8 weeks after syngeneic transplantation and 31 days after allogeneic transplantation, histology of CSPIO-labeled islet grafts showed colocalized insulin and iron staining in the same areas but the size of allografts decreased with time. TEM with elementary iron mapping demonstrated CSPIO distributed in the cytoplasm of islet cells, which maintained intact ultrastructure.
  
  
  CONCLUSIONS
  Our results indicate that after syngeneic and allogeneic transplantation, islets labeled with CSPIO nanoparticles can be effectively and safely imaged by MR.
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital and Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. jjuang@adm.cgmh.org.tw
authors: Jyuhn-Huarng
authors: JH
authors: Juang
authors: Chia-Rui
authors: CR
authors: Shen
authors: Jiun-Jie
authors: JJ
authors: Wang
authors: Chien-Hung
authors: CH
authors: Kuo
authors: Yu-Wen
authors: YW
authors: Chien
authors: Hsiao-Yunn
authors: HY
authors: Kuo
authors: Fu-Rong
authors: FR
authors: Chen
authors: Ming H
authors: MH
authors: Chen
authors: Tzu-Chen
authors: TC
authors: Yen
authors: Zei-Tsan
authors: ZT
authors: Tsai
mesh_terms: D000818:Animals; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D003287:Contrast Media / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D050416:Glucagon-Secreting Cells / Q000378:metabolism / Q000637:transplantation / Q000648:ultrastructure*; D007328:Insulin / Q000096:biosynthesis; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000637:transplantation / Q000648:ultrastructure*; D016381:Islets of Langerhans Transplantation; D007668:Kidney; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D014184:Transplantation, Homologous
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D007328:Insulin; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D048271:Chitosan
references: Nat Med. 2006 Jan;12(1):144-8
references: 16380717
references: N Engl J Med. 1986 May 22;314(21):1360-8
references: 3517648
references: Endocr Rev. 2012 Dec;33(6):892-919
references: 22889646
references: Chem Rev. 2004 Dec;104(12):6017-84
references: 15584695
references: N Engl J Med. 2006 Sep 28;355(13):1318-30
references: 17005949
references: Transplantation. 2004 Apr 27;77(8):1133-7
references: 15114073
references: Transplantation. 2009 Jun 15;87(11):1659-66
references: 19502957
references: Transplantation. 2005 Dec 15;80(11):1596-603
references: 16371931
references: Diabetes. 2006 Nov;55(11):2931-8
references: 17065328
references: Am J Transplant. 2005 Jul;5(7):1635-45
references: 15943621
references: Pancreas. 2009 Apr;38(3):293-302
references: 19169173
references: J Clin Invest. 2011 Jan;121(1):442-5
references: 21123946
references: Nat Rev Endocrinol. 2009 Aug;5(8):444-52
references: 19546863
references: Eur Radiol. 2005 Jul;15(7):1369-77
references: 15726379
references: Am J Transplant. 2009 Oct;9(10):2372-82
references: 19681816
references: Contrast Media Mol Imaging. 2009 May-Jun;4(3):135-42
references: 19489041
references: Pediatr Transplant. 2009 Nov;13(7):892-7
references: 19017287
references: Transplantation. 2008 Jan 15;85(1):155-9
references: 18192927
references: Anat Rec (Hoboken). 2008 Dec;291(12):1684-92
references: 18951510
references: Diabetes. 2005 Jul;54(7):2060-9
references: 15983207
references: Transplant Proc. 2010 Dec;42(10):4217-20
references: 21168668
references: Biomaterials. 2007 Mar;28(9):1629-42
references: 17178155
references: Transplant Proc. 2005 Oct;37(8):3496-8
references: 16298640
references: Cell Transplant. 2001 Apr;10(3):277-284
references: 28866945
references: Invest Radiol. 2006 Jul;41(7):560-71
references: 16772849
references: Am J Transplant. 2008 Mar;8(3):701-6
references: 18294167
references: Transplantation. 2008 Apr 27;85(8):1091-8
references: 18431227
references: AJR Am J Roentgenol. 1989 Jan;152(1):167-73
references: 2783272
references: Transplant Proc. 2008 Mar;40(2):444-8
references: 18374096
references: N Engl J Med. 2000 Jul 27;343(4):230-8
references: 10911004
references: Magn Reson Med. 2004 Dec;52(6):1228-33
references: 15562474
references: Cancer Res. 1989 Jul 15;49(14):3776-82
references: 2736519
references: Transplantation. 2010 Dec 27;90(12):1602-6
references: 21197715
references: Diabetes. 2006 Sep;55(9):2419-28
references: 16936189
references: Transplant Proc. 2010 Jul-Aug;42(6):2104-8
references: 20692419
references: World J Gastroenterol. 2007 Dec 21;13(47):6347-55
references: 18081223