The most common tumor in children and adults with NF1 is the neurofibroma, a peripheral nerve sheath tumor composed of Schwann-like cells. While mouse models of plexiform neurofibromas have been developed, Dr. Lu Le, Professor of Dermatology at the University of Texas-Southwestern joined forces with Drs. Corina Anastasaki and David Gutmann to develop a human model of neurofibroma.
To do this, the team took advantage of human stem cell engineering methods, called CRISPR, to develop a series of NF1 patient-specific human induced-pluripotent stem cells (hiPSCs), which they used to create human Schwann-like cells. They found that implanting human NF1 Schwann-like cells into the nerves of mice resulted in the formation of bona fide neurofibromas, thus creating the first human model of this common tumor.
Moreover, they identified the cell that gives rise to cutaneous neurofibromas, and used this information to design mice that develop classic cutaneous neurofibromas, similar to those found in people with NF1. Dr. Le and his team then used these mice to show that drugs that block MEK activity decrease the growth of cutaneous neurofibromas.
Together, these two laboratories established complementary humanized neurofibroma explant and first-in-kind mouse genetically engineered cutaneous neurofibroma models amenable to future therapeutic target discovery and evaluation.
This report was published in the Journal of Clinical Investigation.