Development of reconstructed human skin by tissue engineering for the modelling and study of neurofibromatosis type 1

Neurofibromatosis Type 1 (NF1) is a disease characterized by the development of cutaneous tumours along nerve pathways. Cutaneous tumours are benign tumours, but have the potential to become malignant over time. To date, there has been no in vitro model making it possible to study the appearance and formation of cutaneous neurofibromas. Moreover, the genetic and pathological mechanisms of the disease and the appearance of cutaneous manifestations in NF are also widely unknown. No specific treatment is available for patients. Only the numerous complications may be treated or controlled. The general objective of the research project is to create an in vitro model, through tissue engineering, of the morphogenesis process of cutaneous neurofibromas. The development of a human skin model reconstructed in a laboratory could represent a renewable source of human tissue. This project would therefore have a considerable impact on the understanding of pathogenic mechanisms leading to the formation of cutaneous neurofibromas and, ultimately, on the identification of therapeutic agents capable of slowing or even preventing the development of cutaneous neurofibromas.


The goal of this project is to create an in vitro model through tissue engineering of the process of morphogenesis of neurofibromas.


  • Objective 1: Create a cell bank of NF1 and NF2 patients, that includes skin cells (fibroblasts, keratinocytes) and cells extracted from cutaneous neurofibromas

  • Objective 2: Create an in vitro model of the morphogenesis of neurofibromas through tissue engineering in skin reconstructed in the laboratory

  • Objective 3: Study the in vitro effects of the addition to the model of pharmacological molecules or other types of isolated neurofibroma cells from patients


To date, we have succeeded in establishing a bank of isolated fibroblasts and keratinocytes from the skin of 14 NF1 and NF2 patients. We continue to work on the development and optimization of a reliable protocol for the extraction of Schwann cells derived from cutaneous neurofibromas. The model of reconstructed skin derived from patients is already well established. We are now attempting to recreate the tumours inside our skin model following the addition of Schwann cells, isolated from neurofibromas. We have observed very interesting preliminary results that demonstrate a strong densification of cells in the equivalent. Is this a prelude to the formation of cutaneous neurofibromas or schwannomas, as they are described in the literature? Time will tell, but we can already hope that the research project will have a considerable impact on the comprehension of cellular and molecular mechanisms involved in the development of neurofibromas. This model could also allows us to target medicine banks in order to identify new therapeutic treatments to reduce, slow, or even prevent the formation of these cutaneous tumours.


Our exceptional research team includes many individuals with varied professional and scientific backgrounds. The participation of each one will allow us to explore the topic presented herein more widely. Our team consists of a neurologist, Dr Nicolas Dupré, a neurosurgeon, Dr Hélène Khuong, a neuropathologist, Dr Peter Gould, a fundamental researcher, Dr François Gros-Louis, who hold the position of Research Chair of Canada in biomodels and treatment of brain diseases, as well as his research group dedicated to the project, composed of a research assistant, Lydia Touzel-Deschênes, and a PhD student, Vincent Roy. Furthermore, the research group evolves in the clinic for neuromuscular and neurogenetic diseases of the CHU de Québec at the Hôpital de l’Enfant-Jésus. Our multidisciplinarity and the synergy between us contribute greatly to the advancement of our research.


Dr François Gros-Louis