Good glycemic control is critical in reducing the end-stage complications of Type I Diabetes Mellitus (TIDM) and, for this reason, islet transplantation (ITx) has received considerable attention in recent years, with one of the complications in the treatment involves finding an effective means to prevent rejection. Immuno-isolation of islets provides a means to reduce or avoid immunosuppressive therapy altogether. In the most commonly used method of immuno-isolation, microencapsulation, individual islets are surrounded with thin alginate membranes that are permeable to insulin and metabolites, but are impermeable to native antibodies. However, the viability and in particular the insulin secretion of these islets are critical for the success of the therapy, and would be important to monitor for refinement of the treatment protocol. This proposal is focused on the production of micron sized CEST MR detectable alginate capsules containing both islet and mesenchymal stem cells which are appropriate for the treatment of T1DM. These capsules will have CEST MR contrast agents built into the capsule to allow: 1) detection, 2) discrimination between encapsulated islet and mesynchymal stem cells and 3) remote sensing of the pH of the environment. The source of the CEST contrast will be 6-24 amino acid long peptides and CEST liposomes embedded within the alginate. We will perform pre-clinical studies using a nude based mouse model of diabetes to allow monitoring of the status of encapsulated islets/ mesenchymal cells through firefly luciferase expression.

Public Health Relevance

Islet transplantation (ITx) has received considerable attention in recent years for treatment of Type 1 Diabetes Melitus (T1DM). This proposal is focused on the production of immunoprotective islet cell capsules which are appropriate for treatment and allow MR monitoring of the pH these islets using biodegradable CEST contrast agents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB012590-03
Application #
8323997
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Liu, Christina
Project Start
2010-09-22
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$348,195
Indirect Cost
$131,925
Name
Hugo W. Moser Research Institute Kennedy Krieger
Department
Type
DUNS #
155342439
City
Baltimore
State
MD
Country
United States
Zip Code
21205
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Song, Xiaolei; Yang, Xing; Ray Banerjee, Sangeeta et al. (2015) Anthranilic acid analogs as diamagnetic CEST MRI contrast agents that feature an intramolecular-bond shifted hydrogen. Contrast Media Mol Imaging 10:74-80
Yang, Xing; Yadav, Nirbhay N; Song, Xiaolei et al. (2014) Tuning phenols with Intra-Molecular bond Shifted HYdrogens (IM-SHY) as diaCEST MRI contrast agents. Chemistry 20:15824-32
Chan, Kannie W Y; Yu, Tao; Qiao, Yuan et al. (2014) A diaCEST MRI approach for monitoring liposomal accumulation in tumors. J Control Release 180:51-9
Chan, Kannie W Y; Bulte, Jeff W M; McMahon, Michael T (2014) Diamagnetic chemical exchange saturation transfer (diaCEST) liposomes: physicochemical properties and imaging applications. Wiley Interdiscip Rev Nanomed Nanobiotechnol 6:111-24
Chan, Kannie W Y; Liu, Guanshu; van Zijl, Peter C M et al. (2014) Magnetization transfer contrast MRI for non-invasive assessment of innate and adaptive immune responses against alginate-encapsulated cells. Biomaterials 35:7811-8
Yadav, Nirbhay N; Xu, Jiadi; Bar-Shir, Amnon et al. (2014) Natural D-glucose as a biodegradable MRI relaxation agent. Magn Reson Med 72:823-8
Chan, Kannie W Y; Liu, Guanshu; Song, Xiaolei et al. (2013) MRI-detectable pH nanosensors incorporated into hydrogels for in vivo sensing of transplanted-cell viability. Nat Mater 12:268-75
Liu, Guanshu; Song, Xiaolei; Chan, Kannie W Y et al. (2013) Nuts and bolts of chemical exchange saturation transfer MRI. NMR Biomed 26:810-28
Bar-Shir, Amnon; Gilad, Assaf A; Chan, Kannie W Y et al. (2013) Metal ion sensing using ion chemical exchange saturation transfer 19F magnetic resonance imaging. J Am Chem Soc 135:12164-7

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