Show results for
  • Sygnature
  • News
  • Drug Discovery
  • Therapeutic Areas
  • Events
  • Vacancies

The application of Design of Experiment to optimise a spheroid model of kidney fibrosis

Fibrosis, the accumulation of scar tissue in response to a variety of physiological and environmental insults, can lead to progressive organ failure. The quantification of fibrosis biomarkers in in vitro models is a powerful tool for assessing novel
anti-fibrotics, but these models have historically been poor predictors of in vivo efficacy due to complicated disease provenance and pathophysiology. There is growing recognition that 3-dimensional (3D) cellular models may offer superior
predictivity by better recapitulating the complexity of diseased tissue. In this poster, we present the development of a 3D in vitro rat kidney spheroid assay to improve translation to in vivo models.
As more traditional One Factor at a Time (OFAT) optimisation of assay parameters is unrealistic for protracted fibrosis assays, we utilised a Design of Experiment (DoE) approach to evaluate multiple non-linear parameters simultaneously in a
Design Expert statistical model. A D-optimal Response Surface model was developed to determine the parameters essential for evolution of a fibrotic phenotype by NRK-49F spheroids. DoE enabled a rapid and comprehensive evaluation of the
assay design space. Testing 200 conditions across 5 numeric and 3 categorical parameters, we optimised our model for screening small molecules and validated against known TGF-b1 signalling inhibitors. Assay quality and response window
were improved over the corresponding 2D assay.

Download Poster

Poster download form with organisation field
Invalid email address provided.
Please only use your business email address.