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Adaptable pulsatile flow generated from stem cell-derived cardiomyocytes using quantitative imaging-based signal

Tongcheng Qian1, Daniel A Gil, Emmanuel Contreras Guzman

  • 1Morgridge Institute for Research, Madison, WI 53715, USA. tqian5@wisc.edu.

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|October 13, 2020
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Summary

Researchers developed an adaptable pump (Adapt-Pump) to create pulsatile blood flow from cardiac spheroids. This system models endothelial cell (EC) behavior under various shear stresses, revealing abnormal EC organization in disease models.

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Area of Science:

  • Cardiovascular Research
  • Cell Biology
  • Biomedical Engineering

Background:

  • Endothelial cells (ECs) are crucial for cardiovascular health, constantly influenced by mechanical forces like fluidic shear stress from blood flow.
  • Understanding EC behavior under diverse shear stress conditions requires advanced methods to generate physiologically and pathologically relevant pulsatile flows.

Purpose of the Study:

  • To introduce and validate an adaptable pump (Adapt-Pump) platform for generating pulsatile flows using human pluripotent stem cell-derived cardiac spheroids (CS).
  • To investigate endothelial cell responses to varying mechanical microenvironments simulated by the Adapt-Pump system.

Main Methods:

  • Development of the Adapt-Pump platform capable of generating pulsatile flows from CS.
  • Utilizing quantitative imaging-based signal transduction to analyze CS contraction characteristics.
  • Differentiating and exposing ECs to pulsatile flows generated under normal and pathological (long QT syndrome) conditions.

Main Results:

  • The Adapt-Pump system successfully recapitulated unique CS contraction patterns and drug responses.
  • Simulations showed CS contraction changes in response to fluidic mechanical stimulation.
  • ECs exposed to pathological pulsatile flow derived from long QT syndrome models exhibited abnormal monolayer organization.

Conclusions:

  • The Adapt-Pump platform is a powerful tool for modeling the cardiovascular system and studying EC behavior.
  • This system enhances our understanding of how mechanical microenvironments affect endothelial cells, with implications for cardiovascular disease research.