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A new flow co-culture system for studying mechanobiology effects of pulse flow waves

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Abstract

Artery stiffening is known as an important pathological change that precedes small vessel dysfunction, but underlying cellular mechanisms are still elusive. This paper reports the development of a flow co-culture system that imposes a range of arterial-like pulse flow waves, with similar mean flow rate but varied pulsatility controlled by upstream stiffness, onto a 3-D endothelial-smooth muscle cell co-culture. Computational fluid dynamics results identified a uniform flow area critical for cell mechanobiology studies. For validation, experimentally measured flow profiles were compared to computationally simulated flow profiles, which revealed percentage difference in the maximum flow to be <10, <5, or <1% for a high, medium, or low pulse flow wave, respectively. This comparison indicated that the computational model accurately demonstrated experimental conditions. The results from endothelial expression of proinflammatory genes and from determination of proliferating smooth muscle cell percentage both showed that cell activities did not vary within the identified uniform flow region, but were upregulated by high pulse flow compared to steady flow. The flow system developed and characterized here provides an important tool to enhance the understanding of vascular cell remodeling under flow environments regulated by stiffening.

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Acknowledgments

The authors wish to thank CVP group for providing the cells and acknowledge funding from American Heart Association (SDG 2110049 to W.T.), and NIH (HL K25 097246 to W.T., HL T32 072738 to R.S.).

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Authors and Affiliations

  1. Department of Mechanical Engineering, University of Colorado at Boulder, Boulder, CO, 80309, USA

    Devon Scott-Drechsel, Zhenbi Su, Robin Shandas & Wei Tan

  2. Department of Bioengineering, University of Colorado at Denver, Aurora, CO, 80045, USA

    Kendall Hunter, Min Li, Robin Shandas & Wei Tan

  3. Department of Pediatrics-Cardiology, University of Colorado at Denver, Aurora, CO, 80045, USA

    Kendall Hunter, Min Li, Robin Shandas & Wei Tan

Authors
  1. Devon Scott-Drechsel
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  2. Zhenbi Su
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  3. Kendall Hunter
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  4. Min Li
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  5. Robin Shandas
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  6. Wei Tan
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Corresponding author

Correspondence to Wei Tan.

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Scott-Drechsel, D., Su, Z., Hunter, K. et al. A new flow co-culture system for studying mechanobiology effects of pulse flow waves. Cytotechnology 64, 649–666 (2012). https://doi.org/10.1007/s10616-012-9445-2

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  • DOI: https://doi.org/10.1007/s10616-012-9445-2

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