Vascular Cells and Tissue Constructs Derived from Human Pluripotent Stem Cells for Toxicological Screening

Stem Cells Dev. 2019 Oct 15;28(20):1347-1364. doi: 10.1089/scd.2018.0246. Epub 2019 Sep 18.

Abstract

The ability of human stem cells to generate somatic cell lineages makes them ideal candidates for use in toxicological testing and eventually, preclinical drug development. Such resources would support an evolution away from human primary cells or research animal models, which suffer from variability and poor predictability, toward off-the-shelf assays of chemical toxicity and drug efficacy using human cells and tissues. To this end, we generated vascular cell populations (smooth muscle cells and endothelial cells) from human pluripotent stem cells (hPSCs), arranged them into 3D co-cultures within supportive gel matrices, and directed their propensity for self-organization resembling microvasculature. The resulting vascular cell populations and co-cultured constructs were then arrayed in high throughput and used for screening a library of environmental and clinical chemical agents for immunological and toxicological responses. The screen effectively stratified the chemicals into various levels of toxicity, with both cell type-specific and co-culture-dependent responses observed. Thus, hPSC-derived vascular cells and constructs could be progressed further toward use in toxicant and drug screening.

Keywords: 3D culture; drug screening; endothelial cell; human pluripotent stem cell; smooth muscle cell; toxicology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Coculture Techniques
  • Dose-Response Relationship, Drug
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • High-Throughput Screening Assays
  • Humans
  • Models, Biological
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / drug effects*
  • Pluripotent Stem Cells / metabolism
  • Small Molecule Libraries / toxicity*

Substances

  • Small Molecule Libraries