用于免疫保护、MR 检测和 pH 传感的 DIACEST 胰岛细胞胶囊-猫眼课题宝

用于免疫保护、MR 检测和 pH 传感的 DIACEST 胰岛细胞胶囊

批准号：

8525116

负责人：

MICHAEL T MCMAHON

金额：

$32.83万

依托单位：

HUGO W. MOSER RES INST KENNEDY KRIEGER

依托单位国家：

美国

项目类别：

财政年份：

2010

资助国家：

美国

项目状态：

已结题

起止时间：

2010-09-22 至 2015-08-31

来源：

https://reporter.nih.gov/project-details/8525116

关键词：

Acute Liver Failure Alginates Amino Acids Antibodies Apoptosis Arginine Attention Biocompatible Cell Line Cell Survival Cell Therapy Cell physiology Cells Chemicals Clinic Clinical Color Contrast Media Crosslinker Detection Diabetic mouse Discrimination Disease Encapsulated Environment Firefly Luciferases Goals Hemophilia A Human Image Imagery In Vitro Individual Insulin Insulin-Dependent Diabetes Mellitus Islet Cell Islets of Langerhans Islets of Langerhans Transplantation Label Libraries Life Lipids Liposomes Magnetic Resonance Magnetic Resonance Imaging Malignant Neoplasms Measures Membrane Mesenchymal Mesenchymal Stem Cells Metals Methods Microencapsulations Monitor Mus Parkinson Disease Patients Peptides Physiological Population Production Reporting Signal Transduction Source Staging Stem cells Streptozocin Techniques Testing Therapeutic immunosuppression Time Toxic effect Treatment Protocols Validation base capsule cell capsule design functional status glycemic control in vivo insulin secretion insulinoma islet mouse model pre-clinical preclinical study prevent public health relevance remote sensing small molecule libraries success

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DESCRIPTION (provided by applicant): 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.

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