High-Throughput Heart-on-a-Chip Platform for Studies of SARS-CoV-2 Induced Myocardial Injury

  • Funded by Canadian Institutes of Health Research (CIHR)
  • Total publications:0 publications

Grant number: 202012MFE

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2022
  • Known Financial Commitments (USD)

    $67,500
  • Funder

    Canadian Institutes of Health Research (CIHR)
  • Principal Investigator

    N/A

  • Research Location

    Canada
  • Lead Research Institution

    University of Toronto
  • Research Priority Alignment

    N/A
  • Research Category

    Clinical characterisation and management

  • Research Subcategory

    Disease pathogenesis

  • Special Interest Tags

    N/A

  • Study Type

    Non-Clinical

  • Clinical Trial Details

    N/A

  • Broad Policy Alignment

    Pending

  • Age Group

    Not Applicable

  • Vulnerable Population

    Not applicable

  • Occupations of Interest

    Not applicable

Abstract

Recent study reported that 78% of the patients recovered from COVID-19 have cardiac involvement and 60% of the patients have ongoing myocardial inflammation based on cardiac magnetic resonance imaging. However, the direct contribution of SARS-CoV-2 infection on the beating cells types of the heart, cardiomyocytes, versus supporting cells that makeup the blood vessels and the matrix as well as immune cells homing to the heart after the infection are not well understood. Human stem cell derived heart-on-a-chip models afford the most direct and efficient route for answering these questions. My preliminary data collected in the CL3 facility demonstrate profound and progressive loss of contractile ability in my heart-on-a-chip platform upon SARS-CoV-2 infection. Stem cell based heart-on-a-chip model is additionally unique as it enables us to systematically study infection on different cell types that make up the heart, an experiment that is not possible in vivo. I will first scale up the production of the heart-on-a-chip platform using 3D printing. I will situate this platform in a 24 well plate, a setting that is suitable for working in biohazard level 3 facility. After infecting the human heart tissue with SARS-CoV-2, I will non-invasively measure how the contractile force changes with time. At the same time, I can collect culture media and determine the extent of inflammation. Through electron microscopy, I will visualize the virus in the human heart tissue. Therapies for covid19 infected heart currently do not exist. I hypothesize that extracellular vesicles derived from healthy cells could represent a viable biological therapy. These consist of a rich mixture of micro RNAs and proteins that are known to be able to protect the heart in other settings, such as loss of oxygen. I will isolate these EVs from healthy cells and apply them to the infected heart-on-a-chip to study preservation of beating function and subsequent improvement.