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MADISON, WI, United States

Invivosciences, Inc. | Date: 2013-10-23

Clinical and laboratory analyzers for measuring, testing, and analyzing biological tissues.

Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 2.09M | Year: 2012

DESCRIPTION provided by applicant Current NIGMS SBIR funding supported InvivoSciences LLCandapos s IVS launch of several product lines in IVS generated revenues from the sales of three dimensional D cell culture tools MC TM and IVS InsertsTM that can grow various hydrogel tissues without any support layers The culture tools enable Palpator TM and Tissue StretcherTM to stretch the hydrogel tissues for biomechanical measurements and mechanical conditioning e g cyclic stress applications respectively IVS also performed contract research services using our tools and devices for industry and academic laboratories for profiling compound induced effects on cell and tissue physiology To further demonstrate our ability to screen drug candidates especially for drug developers the market demands benchmark studies against compounds and drugs whose pharmacological functions including toxicity information have been well characterized To fully commercialize our current start up activities IVS will improve its rapid drug screening system that uses engineered heart tissues EHTs to monitor the effects of test compounds on cardiac contractility and associated regulatory molecules In Aim EHTs will be developed using cardiomyocytes derived from human induced pluripotent stem iPS cells to commercialize a drug screening system using human samples Using this system we will determine the beneficial and toxic effects of a panel of drugs based on the drug induced changes in the cardiac functions of EHTs as well as the signal transduction pathways that underlie their activities In Aim we will establish ISO specified requirements for a quality management system so that we may more confidently provide contract research services for drug developers In addition using a list of well known cardio effective and toxic drugs compounds we will measure drug induced cardiac function changes using EHTs to establish the benchmark In Aim we will identify mechanisms of cardiotoxicity and will demonstrate the ability of the EHTs to predict cardiotoxicity in vitro without the need for establishing animal studies Our approach will advance drug target identification and optimization as well as biomarker discovery critical for diagnosing cardiotoxicity As a demonstration of the ability of our approach to elucidate a mechanism of cardiotoxicity we will use as an example genetic knockdown with shRNA and drugs to inhibit mTOR mammalian target of rapamycin Successful completion of our aims will prove the ability of our in vitro system to predict drug induced cardiotoxicity in humans clearly benefiting early stage drug discovery Existing cardiotoxicity testing in vitro is not sufficient to accurately predict drug induced cardiotoxicity The proposed project will establish a comprehensive cardiotoxicity assessment system using engineered heart tissues fabricated with cardiomyocytes derived from human induced pluripotent stem cells With the new technology drug developers can predict potential drug induced cardiotoxicity at the early stages of drug discovery so will reduce late stage attrition and protect patients from developing cardiac failure

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 91.49K | Year: 2006

DESCRIPTION (provided by applicant): This project will optimize an existing innovative method for performing high-throughput screening assays using engineered tissues that mimic the myocardium and a novel, screening instrument that can rapidly measure the mechanical properties of those tissues. Our engineered tissues significantly reduce the need for whole animal testing. In the proposed research, we will focus on refining our heart tissue model growing in a 96-well format. We will produce samples with identical physiological properties that have Z-factors >0.5 in high-throughput screening assays using our screening instrument. We will perform a blind screen using known compounds with known effects on myocardium to evaluate our measure of success. Further, we will test three drugs, known to affect cardiovascular functions, using an established toxicity assay and our engineered tissue assay system and correlate the results. Our strategic business partner, Gilson, Inc. (Middleton, WI), which has more than 50 years of business development experience in the life science industry, will collaborate with us on the engineering efforts to improve our screening instrument and develop consumable products with our engineered tissues. After confirming the usefulness and reproducibility of the assay, we will profile a small library of plant extracts from the Philippines. The full library of extracts (16,000 samples) is available only to scientists at the Medical College of Wisconsin who collaborate on this project. NCI has previously screened and ranked the extracts in this library for cytotoxicity on HL60 cells. The sub-library consists of 1,045 extracts that showed the lowest toxicity in the NCI study. We will identify "hit" extracts by their ability to alter two important parameters of myocardial contraction measured by our tissue assay system. In Phase II studies, we will focus on characterizing the active components in any extracts that changed myocardial contraction in our assay and screening and profiling the entire library. The ultimate goal of this project is to rapidly and cost-effectively identify an herbal remedy, or compounds from natural products, that could treat cardiovascular diseases.

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 99.37K | Year: 2004

DESCRIPTION (provided by applicant): The availability of libraries containing large numbers of chemical compounds potentially applicable as drugs poses the challenge of screening these compounds for their pharmaceutical utility. High throughput screening methods that measure chemical interactions between the candidate compound and a selected target molecule such as a receptor can screen compounds at high speed, but provide no information about the biological response of cells. As a result many compounds are selected that are inactive biologically or are toxic. Therefore, it is important to have rapid screening methods based on cellular biological responses. The major goal of this proposal is to develop and validate a prototype device that screens compounds based on cellular responses that produce mechanical changes in biological tissue constructs. This approach measures changes of contractile force and stiffness of miniaturized tissue constructs in a format suitable for rapid screening. This approach is advantageous in several respects: . the assay is based on the measurement of a cellular contractile response that is activated by many biologically important signaling pathways; the assay can be carried out rapidly and in a parallel format on many samples; . the assay can be carried out with miniaturized samples to conserve precious materials; . the assay provides quantitative information about cellular and extracellular responses to test compounds; . tissue constructs can be assembled to provide models for specific disease conditions, e.g., elevated contractility of vascular smooth muscle cells in hypertension or fibrosis and cardiovascular remodeling responsible for congestive heart failure or diastolic dysfunction and for scar formation. The specific aims are to optimize a prototype device for measuring mechanical responses of minitissue constructs, to validate the device by comparison with measurements of previously studied tissue constructs and then to demonstrate the utility of this device in a screen for compounds that can regulate blood pressure by reducing contractile force exerted by vascular smooth muscle cells.

Invivosciences, Inc. | Date: 2012-06-06

Engineered cardiac tissues are provided herein. The tissues include cardiomyocyte cells derived from a pluripotent cell, fibroblast cells and extracellular matrix components. Methods of using the tissues described herein are also provided.

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