SBIR-STTR Award

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.

Thesaurus Terms:
Address;Animals;Apoptosis;Bacteria;Base;Cardiac;Cardiac Myocytes;Cardiovascular Diseases;Cardiovascular Disorder Therapy;Cardiovascular System;Cell Count;Cell Division;Cell Physiology;Cell Survival;Cell Therapy;Cell Transplants;Cells;Characteristics;Clinical Trials;Congestive Heart Failure;Contrast Media;Coronary Arteriosclerosis;Data;Daughter Cell;Development;Digestion;Disease;Effective Therapy;Effectiveness;Embryonic Stem Cell;Engineering;Engraftment;Ensure;Family Suidae;Generations;Genome;Goals;Harvest;Heart;Human;Image;Impairment;Implant;In Vitro;In Vivo;Induced Pluripotent Stem Cell;Insight;Iron;Label;Life;Location;Luciferases;Macrophage;Magnetic Resonance Imaging;Magnetism;Mammalian Cell;Medicine;Mesenchymal Stem Cells;Methods;Modeling;Monitor;Mus;Myocardial Infarction;Myocardium;Novel;Optic Imaging;Particle;Phase;Phenotype;Pluripotency;Prevent;Public Health Relevance;Reagent;Regenerative Medicine;Reporter Genes;Reporting;Research Study;Resolution;Safety;Signal Induction;Signal Transduction;Small Business Innovation Research Grant;Specificity;Stem Cell Transplant;Success;Techniques;Technology;Tissues;Tool;Transplantation;Uptake;Use Effectiveness;

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.

Public Health Relevance Statement:


Public Health Relevance:
Project Narrative 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 is 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-invasiv and efficient technology for monitoring transplanted cells in the body using MRI. Our technology can accelerate the development of cell therapies for individuals suffering from diseases such as cancer, neurodegenerative diseases, and cardiovascular disease.

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