Chirurgie plastique et reconstructive pédiatrique
2000-2011 : Congenital Diaphragmatic Hernia in children
Congenital diaphragmatic hernia (CDH) is a defect of the muscle located between the abdominal and the thoracic cavities. Children born with a CDH have two hypoplastic lungs, associated with pulmonary hypertension resulting in hypoxemia, right to left extrapulmonary shunting of blood, acidosis, heart failure and death. CDH occurs in 1/2500 to 1/5000 live births, with an estimated mortality rate of 50%.
The treatment of CDH challenges obstetricians, pediatric surgeons and neonatologists. Depending on prenatal parameters, fetuses with CDH can be classified in “low¨ and “high” risk groups. The fetuses at “high” risk could benefit from prenatal intervention. But even for “low” risk fetuses, mortality at birth remains present despite intensive treatment.
In order to test drugs (anti-hypertension) at birth, to test fetal pulmonary circulation and modulate pulmonary vascular tone, we used lambs with and without CDH created during pregnancy. CDH was surgically created in fetal lambs at 85 days of gestation. Pulmonary hemodynamics were assessed by means of pressure and blood flow catheters (135 days). In vitro, we tested drugs on rings of isolated pulmonary vessels.We tested also the same drugs on isolated pulmonary vessels from near-term fetal lambs with and without CDH. We also try to show by immunohistochemistry the presence of channels in lungs of lambs with CDH.
Six publications were done on this subject
Development and Characterization of a progenitor Skin Cell Bank for Tissue Engineering and its Clinical Application for Acute, Chronic Wounds and Burns
- 2002-2005 and 2010-present :
Wound healing in progenitor skin is characterized by the absence of scar tissue formation, which is not dependent on the intrauterine environment and amniotic fluid. Based on the scarless progenitor skin wound repair model, we postulated that the characteristics of progenitor and adult cells are different, and that the use of progenitor cells may be beneficial for wound healing. Based on cell culture and immunohistochemistry, we showed the difference in resistance against physical and oxidative stress, and in growth capacity between progenitor and adult cells. Progenitor skin cells were shown to grow faster and possess a higher cell turnover rate than adult fibroblasts. They were up to three times more resistant to UVA radiation and about two times more resistant to hydrogen peroxide. Progenitor cells are capable of extraordinary expansion, and we describe herein the development of a progenitor skin cell bank from one single organ donation (4cm2). Therefore, tens of thousands of patients could potentially be treated for acute and chronic wounds from one standardized and controlled cell bank. Progenitor skin cells were seeded onto a collagen matrix to form a three dimensional construct for delivery to burns and acute wounds in children. Clinically, this new technique has been used on both acute and chronic wounds for children that would normally need autografting techniques. Using progenitor skin cell constructs, we are able to eliminate the painful autografting procedures and repair damaged skin completely. Our use of progenitor skin cell constructs resulted in faster and better healing of burns and other wounds in children. The use of tissue engineered fetal skin constructs may provide a simple and efficient therapeutic treatment of wounds and burns of all kinds.
- 2010-present : Transplantation of progenitor human myoblasts: toward new strategies of tissue engineering
Skeletal muscle tissue engineering is a new strategy of tissue repair which aims to reconstruct skeletal muscle defect caused by traumatic injury, burns, congenital malformation or tumor removal. In our laboratory, we have already shown that human progenitor muscular cells seeded on a collagen scaffold were able to be integrated in a wounded mouse muscle without immune rejection. The aim of this study was to analyze the biomechanic properties of this muscle wound healing in our mouse model. We wanted to show that the functional recovery of the repaired tissue repair of a same wounded mouse muscle treated with progenitor skeletal muscle cells associated to the same collagen scaffold. Human muscle progenitor cells from the research cell bank were taken and expanded for the experimentation These human primary progenitor skeletal muscle cells were associated with a collagen scaffold. The right gastrocnemius muscle of C57BL/6 mice were injured with a punch of 4 mm diameter. The injured thigh muscles were partially replaced (hole of 4 mm) either with a collagen scaffold disc with human marked progenitor muscle cells (1x105), with the scaffold disc alone or with nothing. The gastrocnemius muscle on the opposite thighs served as control-samples. An analysis of the force of the muscle contraction as well as the tetanization and the endurance of the muscle was performed at day one and at 8 weeks. We showed that our mouse model was well adapted to test the muscle contractility even after a severe injury. Our preliminary results showed that the absolute peak twitch obtained from the injured muscle was lower than the one obtained from the non-injured contra-lateral muscle at different time point after the intervention. The use of progenitor cells in an injured muscle seemed to improve the absolute peak twitch. Progenitor human cells wer able to engraft on mouse muscle. These cells associated with a collage scaffold were able to improve the functional recovery after a muscle injury.
Retrospective study of the burned patients care at the CHUV and the use of biological bandages: swiss medic (dossier prioritaire, CHUV)
The CHUV/Unit of Regenerative Therapy (hereafter CHUV) has requested Medidee Service SA (hereafter Medidee) to support them in ongoing discussions with the Swiss Competent Authority (SwissMedic) regarding the use of bandages combined with cell therapies (hereafter progenitor biological bandages) in burn care. As Swiss Legal context regulating such therapies changed lately, SwissMedic obliged CHUV to demonstrate safety and performance of these progenitor biological bandages in burn care based on marketing authorization processes. In this perspective, CHUV is willing to establish a formal clinical validation file that will be used to demonstrate the risk/benefit status of the therapy and ensure compliant use of the developed therapy for the benefit of their patients.
CHUV has therefore requested Medidee to perform a review and appraisal of all existing data (published data, unpublished data, literature on equivalent or similar therapies, etc) to establish a first version of the current state of the art. This clinical evaluation report will be used to (1) demonstrate the safety of the progenitor biological bandages and (2) to define a proper clinical strategy associated with appropriate clinical endpoints for use of the progenitor biological bandages.
This clinical evaluation report assesses the clinical risk-benefit ratio of progenitor biological bandages, consisting of human skin progenitor cells seeded on a collagen scaffold, applied on superficial to partial-thickness burn in pediatric and adult patients at the Centre Hospitalier Universitaire Vaudois (CHUV, Burn Center), manufactured by the Cell Production Center at CHUV (CPC), Department of Interdisciplinary Centers (DCI)/Building CHUV-EPCR/CH-1066 Epalinges, which is GMP compliant (Swissmedic authorization N°507482) .
This clinical evaluation report consists of state of the art on burn wound management, a summary of a retrospective clinical study relating to the progenitor biological bandages and of relevant scientific literature currently available, in the aspects of safety, performance, design characteristics, and intended purpose. I am in charged of this retrospective analysis and of the discussion with SwissMedic as medical referent of the ¨projet prioritaire¨ du CHUV
Nos publications peuvent être consultées dans la base de données Unisciences de l'Université de Lausanne.