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Human Induced Pluripotent Stem Cell-Derived Endothelial Cells for Three-Dimensional Microphysiological Systems.

Yosuke K Kurokawa1, Rose T Yin1, Michael R Shang1

  • 11 Department of Biomedical Engineering, Washington University in St. Louis , St. Louis, Missouri.

Tissue Engineering. Part C, Methods
|June 17, 2017
PubMed
Summary

Human induced pluripotent stem cell-derived endothelial cells (iPS-ECs) can create reproducible 3D vascular networks in microphysiological systems (organ-on-a-chip). This advance enhances human disease modeling and overcomes limitations of primary endothelial cells.

Keywords:
endothelial cellsinduced pluripotent stem cellsmicrofluidicsvascularization

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Area of Science:

  • Biomedical Engineering
  • Stem Cell Biology
  • Vascular Biology

Background:

  • Microphysiological systems (MPS) aim to mimic human physiology in vitro.
  • Reproducibility challenges exist due to reliance on primary endothelial cells.
  • Human induced pluripotent stem cell-derived endothelial cells (iPS-ECs) offer a potential solution.

Purpose of the Study:

  • To develop and characterize 3D microvascular networks using iPS-ECs in microfluidic devices.
  • To assess the functionality and stability of iPS-EC-derived vessels.
  • To investigate factors influencing vascular network formation.

Main Methods:

  • Established a CDH5-mCherry reporter iPS cell line.
  • Cultured iPS-ECs in 3D microfluidic devices for 14 days.
  • Performed in vitro assays to evaluate endothelial cell function and vessel stability.
  • Investigated the effect of TGF-β signaling inhibition.

Main Results:

  • iPS-ECs exhibited physiological functions comparable to primary endothelial cells.
  • Stable, perfusable 3D microvascular networks were formed over 14 days.
  • Inhibition of TGF-β signaling enhanced vascular network formation.

Conclusions:

  • iPS-ECs are a viable and reproducible source for endothelial cells in MPS.
  • This approach facilitates human disease modeling.
  • The use of iPS-ECs improves the reproducibility of 3D vascular networks.