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Tracking cardiac engraftment and viability of MiPSC by MRI

通过 MRI 追踪 MiPSC 的心脏移植和活力

基本信息

批准号：
9142123
负责人：
Caleb B. Bell
金额：
$ 98.34万
依托单位：
BELL BIOSYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9142123
关键词：
Address Adoption Adverse effects Affect Anatomy Astrocytes Bacteria Biological Assay Biological Preservation Bioluminescence Capital Cardiac Cardiovascular Diseases Cell Death Cell Therapy Cell Transplants Cell physiology Cells Cessation of life Clinical Clinical Trials Contrast Media Data Development Diagnosis Digestion Disease Engraftment Genetic Engineering Goals Human Image In Vitro Individual Investments Label Left Ventricular Ejection Fraction Life Longitudinal Studies Luciferases Magnetic Resonance Imaging Malignant Neoplasms Measurement Mediating Medicine Microglia Modeling Monitor Morphology Motor Neurons Myocardial Infarction Myocardium Neuraxis Neurodegenerative Disorders Particle Size Phase Positron-Emission Tomography Protocols documentation Rattus Reagent Reporter Genes Risk Rodent Role Safety Signal Transduction Specificity Spinal Cord Stem cells Surface Techniques Technology Therapeutic Thymidine Kinase Tissues Toxic effect Transplantation Validation Work Yang abstracting base biomaterial compatibility commercialization endosymbiont functional improvement functional restoration glial cell-line derived neurotrophic factor imaging agent improved in vivo injured insight macrophage magnetite ferrosoferric oxide nerve injury nerve stem cell public health relevance response tool uptake

项目摘要

DESCRIPTION (provided by applicant): Project Summary/Abstract In order to harness the potential of cell therapies, more needs to be understood about cells post transplantation. Our goal is to experimentally validate magnetoendosymbionts (MEs) as a living MRI contrast agent to provide this insight into stem cell engraftment and viability in cardiac and neural injury model by demonstrating live cell specificity (LCS), in vivo. Bioluminescence and commercial MRI contrast agents will be used as controls for validation and to demonstrate competitive advantages. Reporter gene approaches have LCS but suffer from other complications such as need for genetic engineering that complicates regulatory developments. Existing MRI contrast agents provide full anatomic access, but lack LCS due to uptake by macrophages and nonspecific signal. Our preliminary results suggest that MEs can be used to successfully label cardiomyoctyes (iCMs) and human neural progenitor cells (hNPCs), without perturbing cell function. ME- labeled iCMs were successfully engrafted and visualized for 2 weeks in vivo (the overall goal of Phase 1). Moreover, preliminary results suggest MEs provide LCS whereas the passive MRI agent did not. In Phase 2, we propose to extend from this positive progress and fully demonstrate the value of ME- based cell tracking in a second model (hNPCs) and firmly experimentally define the LCS competitive advantage in both models. Development of imaging reagents that can effectively and specifically label cells in vivo with minimal toxicity addresses critical barrier for the cell therapies. Such a tool will lower the risk of capital investments forR&D and clinical trials, by providing the information on bio-distribution and viability needed to optimize cell therapies.