Cell Culture Model Initiative

A rapid, cost effective way to predict the efficacy of potential drug candidates alone, and in combination.

When NTAP began to work on cutaneous neurofibromas in 2016, the lack of cellular model systems was identified as a major gap in cutaneous neurofibroma (cNF) research. Without this, investigators’ progress was slow due to reliance on costly, time-consuming animal systems to identify agents that might be effective against these tumors.

The NTAP Cell Culture Models initiative addressed a basic need in cNF research: a rapid, cost effective way to predict the efficacy of potential drug candidates alone and in combination.

The range of cell-lines being generated now support multiple applications from quantifiable high throughput screening to secondary assay systems that model the importance of the micro-environment in cNF and the heterogeneity of these tumors.

Projects NTAP funded were focused on building cell culture models that could be used for the following applications:
• Preclinical drug screening
• Exploration of the effects of the mutation type within the NF1 gene on cNF disease pathophysiology
• Elucidation of the critical steps and cell types involved in cNF tumor formation

Visit the index of funded NF1 research programs to learn more about the following NTAP-funded projects and activities to establish a cell culture model that accelerates the search for NF1 therapies.

  • Development of a Novel Plexiform Neurofibroma Farming System for 96-well Plate Drug Screening
  • Development of Plexiform Neurofibroma Cellular Assay for High-Throughput Screening
  • Perpetuating NF1+/- and NF1-/- plexiform neurofibroma-derived tumor cells through the generation of induced pluripotent stem (iPS) cells
  • A primary plexiform neurofibroma cell culture model for use in cell-based high-throughput screens.
  • Plexiform Neurofibroma Model Systems for Preclinical Drug Screening
  • Transition to confirmatory and secondary screening of plexiform neurofibroma models in 96-well format
  • CIDr/NTAP Collaboration: (1) Genetic characterization studies (Cell Line Authentication, SNP Array, Exome Sequencing, and RNA Sequencing) of NF1-/-, NF1-/+, and NF1+/+ cell-lines to be available as tool-set for community, and (2) Analyses conducted by Sage Bionetworks
  • Screening (Single Agent MIPEs, combo): As a result of a collaboration between UFLNTAP, and NCATS, a panel of cell culture systems that represented cNF complexity was used to screen new compounds (as single and combination agents) and identify novel therapeutic targets
  • Validation Studies to validate the results of preliminary HTS at NIH/NCATS by Dr. Ferrer