Vascular organs-on-chip made with patient-derived endothelial cells: technologies to transform drug discovery and disease modeling

Expert Opin Drug Discov. 2024 Mar;19(3):339-351. doi: 10.1080/17460441.2023.2294947. Epub 2023 Dec 20.

Abstract

Introduction: Vascular diseases impart a tremendous burden on healthcare systems in the United States and across the world. Efforts to improve therapeutic interventions are hindered by limitations of current experimental models. The integration of patient-derived cells with organ-on-chip (OoC) technology is a promising avenue for preclinical drug screening that improves upon traditional cell culture and animal models.

Areas covered: The authors review induced pluripotent stem cells (iPSC) and blood outgrowth endothelial cells (BOEC) as two sources for patient-derived endothelial cells (EC). They summarize several studies that leverage patient-derived EC and OoC for precision disease modeling of the vasculature, with a focus on applications for drug discovery. They also highlight the utility of patient-derived EC in other translational endeavors, including ex vivo organogenesis and multi-organ-chip integration.

Expert opinion: Precision disease modeling continues to mature in the academic space, but end-use by pharmaceutical companies is currently limited. To fully realize their transformative potential, OoC systems must balance their complexity with their ability to integrate with the highly standardized and high-throughput experimentation required for drug discovery and development.

Keywords: Blood outgrowth endothelial cell; Vascular disease; disease modeling; drug discovery; endothelial colony forming cell; induced pluripotent stem cells; organ-on-chip.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Discovery
  • Drug Evaluation, Preclinical
  • Endothelial Cells*
  • Humans
  • Induced Pluripotent Stem Cells*
  • Lab-On-A-Chip Devices