The goal of this proposal is to demonstrate the effectiveness of using magneto-endosymbionts for MRI tracking of transplanted iPS cells in the myocardium. MRI is an important technique for visualizing implanted cells because it is non-invasive and provides high anatomical resolution of cell location. Existing MRI contrast reagents have several critical limitations, when used to label mammalian cells, including an uptake of labeled cells by macrophages leading to the persistent, unspecific MRI signal, and induction of changes in labeled cell function. Magneto-endosymbionts have the potential to overcome these limitations by exerting minimal effects on labeled cells and preventing stable macrophage-dependent signal from occurring. The effectiveness of magneto-endosymbionts as a cell tracking reagent will be assessed by monitoring labeled iPS cell in vitro and in the myocardium and comparing the results with that obtained with currently available techniques. Cell therapies are considered extremely promising for treating cardiovascular disease, including myocardial infarction, congestive heart failure, and coronary artery disease. Recently there has been an intense search for novel techniques that can become effective therapies. Here, we will investigate the viability and engraftment of transplanted magneto-endosymbiont labeled iPS in the heart. Optimizing the tools that can help to monitor transplanted cells in vivo can rapidly accelerate the development of effective cell therapies for cardiovascular disease.

Public Health Relevance

Cell therapies are heralding a new era a medicine and have the potential to cure many devastating diseases. The number of clinical trials for cell therapies i rapidly increasing, but many questions about the safety and efficacy of such treatments remain. There is an urgent need for tools that can address these concerns by providing insight into cell function in the body. Bell Biosystems, Inc. is developing a non-invasive and efficient technology for monitoring transplanted cells in the body using MRI. We believe that our technology will be able to overcome some of the issues with conventional imaging reagents and will help to accelerate the development of cardiac therapies for humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43EB019239-01
Application #
8779306
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Liu, Christina
Project Start
2014-09-01
Project End
2015-02-28
Budget Start
2014-09-01
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Bell Biosystems, Inc.
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94107
Lee, Kayla R; Wakeel, Abdul; Chakraborty, Papia et al. (2018) Cell Labeling with Magneto-Endosymbionts and the Dissection of the Subcellular Location, Fate, and Host Cell Interactions. Mol Imaging Biol 20:55-64
Mahmoudi, Morteza; Tachibana, Atsushi; Goldstone, Andrew B et al. (2016) Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes. Sci Rep 6:26960