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

Dian Arifin, Christopher M. Long, Assaf A. Gilad, Christophe Alric, Stéphane Roux, Olivier Tillement, Thomas W. Link, Aravind Arepally, Jeff W Bulte

Research output: Contribution to journalArticle

Abstract

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 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 b TC6 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.

Original languageEnglish (US)
Pages (from-to)790-798
Number of pages9
JournalRadiology
Volume260
Issue number3
DOIs
StatePublished - Sep 2011

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Gadolinium
Islets of Langerhans
Gold
Capsules
Ultrasonography
Tomography
Magnetic Resonance Imaging
Animal Care Committees
Multimodal Imaging
Cell Tracking
Insulinoma
Protamines
C-Peptide
Immunosuppressive Agents
Streptozocin
Type 1 Diabetes Mellitus
Nanoparticles
Lysine
Blood Glucose
Transplantation

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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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. / Arifin, Dian; Long, Christopher M.; Gilad, Assaf A.; Alric, Christophe; Roux, Stéphane; Tillement, Olivier; Link, Thomas W.; Arepally, Aravind; Bulte, Jeff W.

In: Radiology, Vol. 260, No. 3, 09.2011, p. 790-798.

Research output: Contribution to journalArticle

Arifin, Dian ; Long, Christopher M. ; Gilad, Assaf A. ; Alric, Christophe ; Roux, Stéphane ; Tillement, Olivier ; Link, Thomas W. ; Arepally, Aravind ; Bulte, Jeff W. / 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. In: Radiology. 2011 ; Vol. 260, No. 3. pp. 790-798.
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abstract = "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 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 b TC6 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.",
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AU - Long, Christopher M.

AU - Gilad, Assaf A.

AU - Alric, Christophe

AU - Roux, Stéphane

AU - Tillement, Olivier

AU - Link, Thomas W.

AU - Arepally, Aravind

AU - Bulte, Jeff W

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