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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.
MedLine Citation:
PMID:  21734156     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Purpose: To develop microcapsules that immunoprotect pancreatic islet cells for treatment of type I diabetes and enable multimodal cellular imaging of transplanted islet cells. Materials and 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 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 (9.4T) 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. Conclusion: Cell encapsulation with GG provides a means of trimodal noninvasive tracking of engrafted cells. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101608/-/DC1.
Authors:
Dian R Arifin; Christopher M Long; Assaf A Gilad; Christophe Alric; Stéphane Roux; Olivier Tillement; Thomas W Link; Aravind Arepally; Jeff W M Bulte
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-6
Journal Detail:
Title:  Radiology     Volume:  -     ISSN:  1527-1315     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0401260     Medline TA:  Radiology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering; Department of Biomedical Engineering.
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