Cell Culture Model Initiative

A lack of cellular model systems was identified as a major gap in cutaneous neurofibroma (cNF) research, slowing investigators’ progress 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 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 were focused on building cell culture models that can 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 UFL, NTAP, 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