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Human pluripotent stem cell tools for cardiac optogenetics.

Yan Zhuge, Bhagat Patlolla, Charu Ramakrishnan

    Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
    |January 9, 2015
    PubMed
    Summary
    This summary is machine-generated.

    Researchers engineered human embryonic stem cell-derived cardiomyocytes (hESC-CM) to respond to light using channelrhodopsin-2 (ChR2). This optical control of hESC-CM offers a potential strategy to avoid arrhythmias in stem cell therapies.

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    Area of Science:

    • Biomedical Engineering
    • Stem Cell Biology
    • Cardiology

    Background:

    • Arrhythmias are a significant concern for therapies using human pluripotent stem cell (hPSC)-derived cardiomyocytes (CM).
    • Effective therapies require precise control over hPSC-CM function to prevent adverse cardiac events.

    Purpose of the Study:

    • To introduce light-activated channelrhodopsin-2 (ChR2) into human embryonic stem cells (hESC) for optical control of hESC-derived cardiomyocytes (hESC-CM).
    • To evaluate the feasibility of using optical stimulation for activating hESC-CM in vitro and its potential for future in vivo applications.

    Main Methods:

    • Lentiviral vector-mediated transduction of channelrhodopsin-2 (ChR2) into undifferentiated hESCs.
    • Directed differentiation of hESC(ChR2) into cardiomyocytes (hESC(ChR2)-CM).
    • In vitro assessment of optical and electrical stimulation responses of hESC(ChR2)-CM compared to wild-type hESC-CM.

    Main Results:

    • hESC(ChR2)-CM were successfully generated and exhibited light-activated responses to 480 nm light.
    • Optically stimulated hESC(ChR2)-CM showed similar contractility features to electrically stimulated wild-type hESC-CM.
    • Optimal optical activation was observed above specific light intensity and pulse width thresholds.

    Conclusions:

    • A light-sensitive protein (ChR2) can enable in vitro optical control of hESC-CM.
    • Optical stimulation offers a novel method for precise control of hPSC-CM function.
    • Future in vivo optical stimulation and inhibition could synchronize implanted hPSC-CM with patient cardiac rhythms, potentially preventing arrhythmias.