Biofabrication of a three dimensional human-based personalized neurofibroma model

• Published in: Biotechnology journal p. e2000250
• Main Authors: Roy, Vincent, Lamontagne, Rémy, Talagas, Matthieu, Touzel-Deschênes, Lydia, Khuong, Hélène T, Saikali, Stéphan, Dupré, Nicolas, Gros-Louis, François
• Format: Journal Article
• Language: English
• Published: Germany 01.06.2021
• Subjects: neurofibromatosis type 1; tissue engineering; neurofibromas; three dimensional in vitro model; Schwann cells
• ISSN: 1860-7314
• DOI: 10.1002/biot.202000250

Neurofibromas are the most characteristic feature of neurofibromatosis type 1 (NF1), a multisystemic disorder caused by aberrations in the neurofibromin gene (NF1). Despite significant progress over the last several years in understanding this disease, a suitable in vitro model to better mimic neurofibroma formation and growth has yet to be described. There is therefore a need to establish an in vitro, three dimensional model that allows the incorporation of multicellular lineages and the modulation of the cellular microenvironment-known to be important for cellular crosstalk and distribution of soluble factors-to study neurofibroma biology and morphogenesis. A self-assembly approach was used to generate tissue-engineered skins (TES) in which patient-derived spheroids made of NF1-associated Schwann cells and fibroblasts were seeded. We describe the first in vitro three dimensional neurofibroma model-directly derived from NF1 patients presenting with histopathological features-having an ECM protein expression profile quite similar to that of a native tumor. We observed efficient incorporation, proliferation, and migration of spheroids within NF1-TES over time. This biotechnological approach could provide a unique tool for precision medicine targeting NF1 and for assessing the tumorigenic properties of each NF1 gene mutation linked to tumor formation.