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Related Experiment Videos

Phenotypic screening for pharmaceuticals using tissue constructs.

T Wakatsuki1, J A Fee, E L Elson

  • 1Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 South Euclid Ave, St Louis, MO 63110, USA.

Current Pharmaceutical Biotechnology
|April 14, 2004
PubMed
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Researchers developed advanced tissue constructs for phenotypic screening, enabling early identification of toxic compounds and assessment of cellular mechanical functions. This method complements molecular screening by evaluating drug effects on cell and tissue structure and function.

Area of Science:

  • Biotechnology and Pharmaceutical Sciences
  • Cellular and Tissue Engineering
  • Drug Discovery and Development

Background:

  • Pharmaceutical compound screening traditionally involves molecular screening (target-based) or phenotypic screening (cell/tissue-based).
  • Molecular screening, enhanced by fluorescence methods, offers high throughput but lacks cellular function insights.
  • Phenotypic screening provides crucial cellular response data but is often slower.

Purpose of the Study:

  • To develop advanced tissue constructs for improved phenotypic screening.
  • To assess the utility of these constructs in evaluating drug effects on cellular mechanical functions and structure.
  • To complement high-throughput molecular screening with functional cellular data.

Main Methods:

  • Reconstitution of tissue constructs using specific cell types and extracellular matrix components.

Related Experiment Videos

  • Utilizing these constructs to detect compound effects on cellular mechanical functions (e.g., contractile force).
  • Evaluating compound impacts on cell and matrix structure and stiffness.

    • Main Results:

    • Demonstrated the ability of tissue constructs to provide information on cellular contractile force, aiding in the identification of agents affecting blood pressure.
    • Successfully produced tissue constructs mimicking skeletal, smooth, and heart muscles, as well as connective tissues.
    • These constructs allow for the study of mechanical and structural responses to active compounds.

    Conclusions:

    • Tissue constructs offer a valuable platform for phenotypic screening, providing insights into cellular mechanical functions and structural integrity.
    • This approach can identify compounds with desired cellular effects and eliminate toxic agents early in the drug discovery process.
    • The developed constructs represent a significant advancement for studying drug responses in physiologically relevant tissue models.