title: Trimodal gadolinium-gold microcapsules containing pancreatic islet cells restore normoglycemia in diabetic mice and can be tracked by using US, CT, and positive-contrast MR imaging.
abstract: OBJECTIVE
  To develop microcapsules that immunoprotect pancreatic islet cells for treatment of type I diabetes and enable multimodal cellular imaging of transplanted islet cells.
  
  
  METHODS
  All animal experiments were approved by the institutional animal care and use committee. Gold nanoparticles functionalized with DTDTPA (dithiolated diethylenetriaminepentaacetic acid):gadolinium chelates (GG) were coencapsulated with pancreatic islet cells by using protamine sulfate as a clinical-grade alginate cross linker. Conventional poly-l-lysine-cross-linked microcapsules and unencapsulated islets were included as controls. The viability and glucose responsiveness of islet cells were assessed in vitro, and in vivo insulin (C-peptide) secretion was monitored for 6 weeks in (streptozotocin-induced) diabetic mice with (n = 7) or without (n = 8) intraabdominally engrafted islet cells. Five nondiabetic mice were included as controls. Differences between samples were calculated by using a nonparametric Wilcoxon Mann-Whitney method. To adjust for multiple comparisons, a significance level of P < .01 was chosen. Generalized estimating equations were used to model cell function over time. Three mice with engrafted capsules were imaged in vivo with high-field-strength (9.4-T) magnetic resonance (MR) imaging, micro-computed tomography (CT), and 40-MHz ultrasonography (US).
  
  
  RESULTS
  Encapsulated human pancreatic islets were functional in vitro for at least 2 weeks after encapsulation. Blood glucose levels in the diabetic mice transplanted with GG-labeled encapsulated mouse βTC6 insulinoma cells returned to normal within 1 week after transplantation, and normoglycemia was sustained for at least 6 weeks without the use of immunosuppressive drugs. GG microcapsules could be readily visualized with positive-contrast high-field-strength MR imaging, micro-CT, and US both in vitro and in vivo.
  
  
  CONCLUSIONS
  Cell encapsulation with GG provides a means of trimodal noninvasive tracking of engrafted cells.
authors: Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 720 Rutland Ave, 217 Traylor, Baltimore, MD 21205, USA.
authors: Dian R
authors: DR
authors: Arifin
authors: Christopher M
authors: CM
authors: Long
authors: Assaf A
authors: AA
authors: Gilad
authors: Christophe
authors: C
authors: Alric
authors: Stéphane
authors: S
authors: Roux
authors: Olivier
authors: O
authors: Tillement
authors: Thomas W
authors: TW
authors: Link
authors: Aravind
authors: A
authors: Arepally
authors: Jeff W M
authors: JW
authors: Bulte
mesh_terms: D000818:Animals; D002214:Capsules; D058948:Cell Tracking / Q000379:methods*; D003921:Diabetes Mellitus, Experimental / Q000175:diagnosis* / Q000601:surgery*; D005682:Gadolinium; D006046:Gold; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome; D014463:Ultrasonography / Q000379:methods
chemical_list: D002214:Capsules; D006046:Gold; D005682:Gadolinium