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Related Experiment Videos

Genetically engineered biologically based hemostatic bioassay.

Lilong Tang1, David J Christini, Jay M Edelberg

  • 1Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.

Annals of Biomedical Engineering
|March 12, 2003
PubMed
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Researchers engineered cardiac myocytes to detect thrombin, a key clotting protein. This novel biosensor shows promise for real-time monitoring of blood coagulation in vivo, aiding treatment optimization.

Area of Science:

  • Biomedical Engineering
  • Cardiovascular Research
  • Cellular Engineering

Background:

  • Real-time in vivo monitoring of hemostatic parameters is crucial for optimizing coagulation-modifying pharmacotherapies.
  • Existing in vivo sensors have limited capacity to monitor thrombotic and hemostatic activity due to restricted sensory inputs.

Purpose of the Study:

  • To develop a genetically engineered excitable cell line for an implantable thrombin biosensor.
  • To overcome limitations of current sensors in monitoring thrombotic and hemostatic activity.

Main Methods:

  • Generated stem cell-derived cardiac myocyte aggregates overexpressing the human thrombin receptor, protease activated receptor-1 (PAR-1).
  • Exploited the inherent electropotential input-output relationship of engineered cells to detect local thrombin activity.

Related Experiment Videos

  • Assessed cellular response to thrombin in vitro (cAMP levels) and in vivo (chronotropic activity).

    • Main Results:

    • PAR-1 cardiac myocytes showed a sixfold increase in intracellular cAMP in response to thrombin in vitro, compared to twofold in control cells.
    • Implanted PAR-1 engineered cells in vivo detected local thrombin increases, doubling chronotropic activity versus a 50% increase in control aggregates.
    • Demonstrated that genetic engineering can expand the range of physiological signals recognized by excitable cells.

    Conclusions:

    • Genetically engineered cardiac myocytes expressing PAR-1 can function as a biosensor for thrombin.
    • This approach shows potential for real-time in vivo monitoring of hemostatic function.
    • Facilitates translation for dynamic pharmacotherapy delivery and coagulation management.