Francesca Moretti

Originally from Rome, Italy, earned a PhD in Molecular Biology from the European Molecular Biology Laboratory in Heidelberg, Germany. Trained in cell biology, high content imaging and genetic screening as an EMBO Long-Term postdoctoral fellow at the Department of biomedicine of the University of Basel and, subsequently, at the Chemical Biology and Therapeutics department of NIBR (Novartis Institutes for BioMedical Research). Since November 2019, leading the Cellular Models lab in the Preclinical Safety Department at Novartis and supporting in vitro mechanistic safety assessment of compounds across all stages of development.

NextGen Basel 1

3D vessel on-chip system for the assessment of vascular toxicities

Vascular toxicity can be observed during pre-clinical and clinical development of novel compounds. Drug-induced endothelial dysfunction can manifest, for example, as increased adhesiveness and transmigration of leukocytes, increased endothelial barrier permeability and/or perturbation of angiogenesis. We set out to evaluate 2D and 3D human endothelial cell models for their ability to recapitulate drug-induced vascular toxicity. We used the Mimetas OrganoPlate system to generate 3D endothelial tubes subjected to gravity-driven perfusion and compared them to 2D static endothelial cell cultures. We observed that 2D static endothelial cell cultures are better suited to recapitulate vascular inflammation and leukocyte adhesion than 3D cultures. The 3D cultures allowed us to perform assessment of endothelial barrier integrity and recapitulate vascular leakage findings from the clinic. Furthermore, the 3D cultures allowed the establishment of angiogenic sprouting and the evaluation of compounds with both pro- and anti-angiogenic potential. In summary, we have established a combination of 2D and 3D cellular assay that allow the identification and characterization of various human vascular toxicities.