Dr. Véronique J. Moulin is a professor at Université Laval’s Faculty of Medicine, Department of Surgery, and a researcher and director of the Regenerative Medicine Division at the CHU de Québec Research Center. Her work focuses on the normal and pathological mechanisms of skin healing. To achieve this, she uses various cell culture models reconstituted through tissue engineering to reproduce fibrotic skin diseases in vitro, such as hypertrophic scars or systemic scleroderma. Understanding these mechanisms aims to identify new treatments to prevent or cure the formation of fibrotic tissues. Simultaneously, she employs tissue engineering methods to reconstruct substitutes for patient treatment. She is leading a nationwide clinical trial in Canada to evaluate the efficacy and safety of in vitro autologous reconstructed skin for treating patients with burns covering more than 50% of their bodies. Her research is funded by CIHR, NSERC, the Stem Cell Network, TheCell Network, and the Canadian Foundation for Innovation. She has published approximately 80 scientific articles, reviews, and book chapters, and has been invited to present her findings at numerous international conferences.

Title: Setting up the conditions for the biobanking of tissues and cells from hypertrophic scars

Lay Abstract: Hypertrophic scars (Hsc) are very common sequelae of deep wounds in general but especially following burns. However, treatments of these pathological scars show a low efficacy whereas the level of research in Canada is low. To stimulate research in this field, access to the human tissues or cells is needed. Our goal is to set up the conditions to create a biobank dedicated to Hsc. We are therefore requesting funds to carry out the administrative work to set up the conditions for a biobank including Hsc samples as well as normal skin samples from the same patients. This project will be carried out in 4 main steps: 1. Determine the area and number of biopsies that can be taken to allow for maximum studies; 2. Obtain ethical and administrative approval to begin biobanking; 3: Develop a protocol and train research staff to process, store and ship samples. 4: Perform the first biopsies to evaluate the process. The ability for researchers to have access to a biobank is a factor that will encourage them to focus on this condition and find a way to treat it.

Scientific Summary: Hypertrophic scars (Hsc) are very common sequelae of deep wounds in general but especially after burns. However, treatments of these pathological scars show low efficacy while the level of research in Canada is low. To stimulate research in this field, access to human tissues or cells is necessary. Our goal is to put in place the conditions to create a biobank dedicated to Hsc. We are therefore requesting funds to do the administrative work to set up the conditions for a biobank including Hsc samples as well as normal skin samples from the same patients. This project will have 4 main steps: 1. Determine the area and number of biopsies that can be taken to allow for maximum studies; 2. Obtain ethical and administrative approval to begin biobanking; 3: Develop a protocol and train research staff to process, store and ship the samples. 4: Perform the first biopsies to evaluate the process. The ability for researchers to have access to a biobank is a factor that will encourage them to focus on this condition and find a way to treat it.

The research group is composed of a basic scientist who work with cells and tissues to understand fibrosis, 2 plastic surgeons who treat Hsc, an ethicist who will help structure the biobank et 2 patient partners that will contribute their insights as patients.

Dr. Lucie Germain is Full professor at the Faculty of Medicine, Université Laval, Québec, Canada. She is director of the LOEX Tissue Engineering Research Center of Laval University. Her research is dedicated to post-natal stem cells and the reconstruction of human tissues for experimental and clinical applications. Dr. Germain is Member of the Canadian Academy of Health Sciences and Fellow of the Tissue Engineering and Regenerative Medicine International Society. She has received the Léo Pariseau Award of ACFAS for her achievement in biologic and health sciences. She published more than 185 peer-reviewed articles, 72 book chapters and review articles. The LOEX invention of a tissue engineering method, the self-assembly approach, led to the development of a bilayered skin substitute, which is very similar to native skin and allow the preservation of stem cells. Her work led to clinical trials on humans involving engineered tissues produced in vitro including autologous bilayer skin substitutes for grafting severely burned patients. The autologous tissues are reconstructed in Québec city in the CHU de Québec-Université Laval/LOEX and grafted to patients in several hospitals of 5 provinces in Canada.

Project title: Epidermolysis bullosa multidisciplinary team focusing on developing an effective cure for this severe rare skin disease.

Lay title: Together to treat epidermolysis bullosa

Lay summary: Epidermolysis bullosa (EB) is a group of rare diseases that cause the skin to blister easily. 300 to 500 patients live with this pathology in Canada. Wounds are very painful and can persist for years or become aggressive skin cancer, which is a major cause of death. Until now, the treatment for these patients is palliative, mainly with bandages to protect epithelial wounds. Since 2022, we have formed a multicenter group gathering clinicians, researchers and patient partners from three Canadian provinces (Quebec, Ontario and British Columbia) in order to find a treatment for this severe rare skin disease. This group has worked together to prepare a multicenter clinical trial for the most severe form of this disease, the recessive dystrophic EB in order that discoveries from the laboratory reach patients. This clinical trial consists of the use of gene therapy combined with tissue engineering to develop genetically corrected skin substitutes that will be grafted on the EB wounds to replace the lost skin. We estimate that patient’s recruitment will begin in 2025. In this proposal, we will extend our team to include persons interested to a therapeutic approach for the other EB forms as the dominant dystrophic EB, the Junctional EB and the kindler syndrome.

Scientific summary: With around 300-500 patients in Canada, epidermolysis bullosa is a group of heterogeneous rare inherited skin disorders in which minor mechanical stress in the skin and mucous membranes causes the formation of blisters and erosions. The severity of this disease varies among subtypes with mild blistering to severe bulla formation, erosions, scarring, mutilation and lethal outcome. Current treatment is strictly palliative which severely compromise the quality of life for patients and their families. This underlines the need for effective treatment options. The LOEX (CHU de Québec-Université Laval), one of the leading organ reconstruction labs in the world, invented the autologous self-assembled skin substitute (SASS) therapy for burn patients since 2005. The discussion about a clinical trial for the recessive dystrophic EB (RDEB) form has been initiated in the LOEX. Our approach consists of the production of a gene modified epidermolysis bullosa-self assembled skin substitute (GMEB-SASS) by combining gene therapy and tissue engineering. All the required preclinical tests were achieved and showed results that support the safety and efficacy of the proposed approach to cure the disease in the treated areas as well as the long-term skin durability and wound healing. The required documentation for regulatory approval were finalized with the required reports and submitted to Health Canada. The design and the progress of the preparation of the clinical trial was regularly discussed in our multicenter group meetings with patients, researchers and clinicians. We are aiming to start the phase I/II clinical trial in 2025 in accordance with the Good Clinical Practices (GCP). This will be a first-in-human clinical trial to test the safety and advantages of gene-modified epidermolysis bullosa-self-assembled skin substitute (GMEB-SASS) for RDEB treatment. In the present proposal, our multicenter collaborative skin research group will continue the implementation of the clinical trial for RDEB and consider expanding our ambitious therapeutic approach to other EB forms.