Magnetization transfer contrast MRI for non-invasive assessment of innate and adaptive immune responses against alginate-encapsulated cells

Chan, Kannie W. Y.; Liu, Guanshu; Zijl, Peter C.M. van; Bulte, Jeff W.M.; McMahon, Michael T.

doi:10.1016/j.biomaterials.2014.05.057

Cited by 16 publications

(18 citation statements)

References 54 publications

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“…After transfer of their saturation to bulk water, from which the proton MRI signal is derived, the water signal is reduced; hence these exchangeable protons are detected indirectly. CEST imaging is now being recognized as an emerging technique for molecular and cellular MR imaging: it can be used to detect MRI reporter genes [15–17], enzyme activity [18], pH changes associated with cell death [14], and the occurrence of an immune response against foreign body materials [19]. …”

Section: Discussionmentioning

confidence: 99%

Label-free imaging of gelatin-containing hydrogel scaffolds

et al. 2015

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Composite hyaluronic acid (HA) hydrogels containing gelatin are used in regenerative medicine as tissue-mimicking scaffolds for improving stem cell survival. Once implanted, it is assumed that these biomaterials disintegrate over time, but at present there is no non-invasive imaging technique available with which such degradation can be directly monitored in vivo. We show here the potential of chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) as a label-free non-invasive imaging technique to monitor dynamic changes in scaffold composition in vivo. The CEST properties of the three individual hydrogel components (HA, gelatin-GelinS, and polyethylene glycol diacrylate) were first measured in vitro. The complete hydrogel was then injected into the brain of immunodeficient rag2−/− mice and CEST MR images were obtained at day 1 and 7 post-transplantation. In vitro, GelinS gave the strongest CEST signal at 3.6 ppm offset from the water peak, originating from the amide protons present in gelatin. In vivo, a significant decrease in CEST signal was observed at 1 week post-implantation. These results were consistent with the biodegradation of the GelinS component, as validated by fluorescent microscopy of implanted hydrogels containing Alexa Fluor 488-labeled GelinS. Our label-free imaging approach should be useful for further development of hydrogel formulations with improved composition and stability.

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Section: Discussionmentioning

confidence: 99%

Label-free imaging of gelatin-containing hydrogel scaffolds

et al. 2015

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“…Using magnetic transfer ratio MRI images, Chan et al quantified differences in local immune response to implanted alginate microbeads both with and without cells and in the presence and absence of immunosuppression therapy. 63 This study demonstrated how MRI can be used to detect variances in the local response to the implant.…”

Section: Discussionmentioning

confidence: 99%

Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast

Appel

Ibarra

Somo

et al. 2016

Tissue Engineering Part C: Methods

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Transplantation of functional islets encapsulated in stable biomaterials has the potential to cure Type I diabetes. However, the success of these materials requires the ability to quantitatively evaluate their stability. Imaging techniques that enable monitoring of biomaterial performance are critical to further development in the field. Xray phase-contrast (XPC) imaging is an emerging class of X-ray techniques that have shown significant promise for imaging biomaterial and soft tissue structures. In this study, XPC imaging techniques are shown to enable three dimensional (3D) imaging and evaluation of islet volume, alginate hydrogel structure, and local soft tissue features ex vivo. Rat islets were encapsulated in sterile ultrapurified alginate systems produced using a highthroughput microfluidic system. The encapsulated islets were implanted in omentum pouches created in a rodent model of type 1 diabetes. Microbeads were imaged with XPC imaging before implantation and as whole tissue samples after explantation from the animals. XPC microcomputed tomography (mCT) was performed with systems using tube-based and synchrotron X-ray sources. Islets could be identified within alginate beads and the islet volume was quantified in the synchrotron-based mCT volumes. Omental adipose tissue could be distinguished from inflammatory regions resulting from implanted beads in harvested samples with both XPC imaging techniques. Individual beads and the local encapsulation response were observed and quantified using quantitative measurements, which showed good agreement with histology. The 3D structure of the microbeads could be characterized with XPC imaging and failed beads could also be identified. These results point to the substantial potential of XPC imaging as a tool for imaging biomaterials in small animal models and deliver a critical step toward in vivo imaging.

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“…It could also be advantageous to develop imaging techniques to show local tissue response to the transplanted cells and biomaterials because it could help predict the long-term success or failure of the graft. Magnetic Transfer Ratio images produced by MRI have been used to quantify differences in local immune response to implanted alginate microbeads both with and without cells as well as in the presence and absence of immunosuppression therapy (88). X-ray Phase Contrast (XPC) imaging is also an emerging technique that allows for visualization of biomaterials and soft tissue (89).…”

Section: More Recently Investigators Have Moved From Labeling the Cementioning

confidence: 99%

Long-Term Function of Alginate-Encapsulated Islets

Köllmer

Appel

Somo

et al. 2016

Tissue Engineering Part B: Reviews

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Human trials have demonstrated the feasibility of alginate-encapsulated islet cells for the treatment of type 1 diabetes. Encapsulated islets can be protected from the host's immune system and remain viable and functional following transplantation. However, the long-term success of these therapies requires that alginate microcapsules maintain their immunoprotective capacity and stability in vivo for sustained periods. In part, as a consequence of different encapsulation strategies, islet encapsulation studies have produced inconsistent results in regard to graft functioning time, stability, and overall metabolic benefits. Alginate composition (proportion of M- and G-blocks), alginate purity, the cross-linking ions (calcium or barium), and the presence or absence of additional polymer coating layers influence the success of cell encapsulation. This review summarizes the outcomes of long-term studies of alginate-encapsulated islet transplants in animals and humans and provides a critical discussion of the graft failure mechanisms, including issues with graft biocompatibility, transplantation site, and integrity of the encapsulated islet grafts. Strategies to improve the mechanical stability of alginate capsules and methods for monitoring graft survival and function in vivo are presented.

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Magnetization transfer contrast MRI for non-invasive assessment of innate and adaptive immune responses against alginate-encapsulated cells

Cited by 16 publications

References 54 publications

Label-free imaging of gelatin-containing hydrogel scaffolds

Label-free imaging of gelatin-containing hydrogel scaffolds

Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast

Long-Term Function of Alginate-Encapsulated Islets

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