Transplantation hépatique | EPFL Graph Search

La transplantation hépatique, ou greffe du foie, est une intervention chirurgicale consistant à remplacer un foie malade par un foie sain, prélevé sur un donneur. La transplantation est utilisée comme traitement pour les cirrhoses en phase terminale, les hépatites fulminantes et d'autres syndromes métaboliques ou auto-immuns particuliers touchant le foie. Le foie étant le seul organe du corps humain possédant la capacité de se régénérer, il est possible de réaliser une transplantation hépatique à partir d'un greffon prélevé chez un donneur vivant. Plus fréquemment cependant, le greffon provient d'un donneur déclaré en état de mort encéphalique. Ainsi, la principale technique chirurgicale est la transplantation orthotopique, où le foie malade est remplacé par celui du donneur dans la position anatomique originale. D'autres techniques incluent la transplantation d'un seul lobe (gauche pour les enfants et droit pour les adultes), ou la greffe auxiliaire. Pour éviter le rejet, il est nécessaire d'avoir une compatibilité sanguine optimale et le traitement immunosuppresseur est indispensable. Comme pour les autres greffes d'organes, la greffe hépatique fait l'objet de nombreuses régulations, et est conduite dans des centres de transplantation où travaillent des équipes médicales et chirurgicales spécialisées. première transplantation hépatique réalisée par le Thomas Starzl chez un patient de 3 ans atteint d'une atrésie des voies biliaires ayant conduit à une insuffisance hépatique. L'enfant décède d'une hémorragie lors de l'opération qui a lieu à Denver, Colorado. 1963 : quatre autres interventions infructueuses sont effectuées chez des adultes 1968 : le docteur Jean Paul Clot, avec son maître le professeur Henri Garnier, réalise en France la première greffe du foie suivie d'une survie relativement prolongée pour l'époque 1969 : à Louvain en Belgique, est réalisée par le Kestens et le Otte la première transplantation hépatique en Europe, chez un patient atteint d'une hépatite B qui décédera d'une pneumopathie un mois plus tard.

Advanced metabolite mapping at ultra-high field using 1H-MRS, 1H-MRSI and macromolecules: applications in a rat model of type C hepatic encephalopathy

Dunja Simicic

Magnetic Resonance Spectroscopy (MRS) is the only technique capable of measuring a large number of metabolites simultaneously in vivo. Ultra-high magnetic fields (UHF) combined with ultra-short echo time (TE) sequences allow the detection of high-quality 1H MR spectra and the quantification of 20 different metabolites in the brain (markers of energy metabolism, osmoregulation etc.).In vivo brain localized 1H MR spectra at short TEs contain the contribution of mobile macromolecules (MM). Reliable detection and fitting of MM are crucial for accurate quantification. Higher spectral resolution at UHF led to increased interest in using a parametrized MM spectrum and flexible spline baselines to address unpredicted spectroscopic components.In this thesis the MM spectra (from the rat brain at 9.4T) were characterized using an improved methodological approach for their post-processing, fitting and quantification. This method provided an efficient tool for parametrization of the MM spectrum into individual components and estimation of their T2app relaxation times. An extensive assessment on how the MM spectrum and spline baseline stiffness affect the metabolite and MM quantification is also reported Type C hepatic encephalopathy (HE) is a complication of chronic liver disease (CLD). Children and adults respond differently to CLD and its related toxic accumulation of molecules (i.e. ammonium (NH4+), glutamine (Gln)). Children with CLD may grow up with significant neurocognitive deficits even after liver transplantation. Despite considerable advances in understanding the pathogenesis of type C HE, the exact metabolic mechanisms and their regional variations are not fully understood.The advantages of UHF short TE 1H MRS were used herein to describe the regional distribution of metabolites in the developing and adult brain using the bile duct ligated model (BDL) of type C HE (adult and postnatal day 21 rats). Three brain regions were assessed (hippocampus, cerebellum and striatum) pointing towards cerebellum as a region with the heaviest burden of Gln and unique metabolic response. Changes in cell morphology were followed longitudinally and related to the metabolic alterations. Elevated oxidative stress is reported using electron paramagnetic resonance, together with the decreased antioxidants (1H MRS) emphasizing its important role in HE. The brain regional measurements confirmed the higher susceptibility of developing brain to the disease and the increased vulnerability of cerebellum. Finally, the beneficial effect of Cr supplementation on the neurometabolic profile is described using 1H MRS and 31P MRS in CLD pups (BDL at postnatal day 15) suggesting that an appropriate treatment may have significant public health impact.MRSI is a powerful tool to non-invasively and spatially map the brain regional distribution of metabolites in vivo. While MRSI in human brain is increasingly used, preclinical MRSI is not widely applied mainly due to the small rodent brain, long acquisition times and low signal to noise ratio. The implementation of a novel approach: free induction decay (FID) MRSI on the 14.1T preclinical scanner is described herein. This method offers a fast and robust data acquisition with high spatial resolution resulting in high quality spectroscopic maps. Finally, preliminary assessment of the effect of two noise reduction techniques (MP-PCA and TGV reconstruction) on the spectra from preclinical MRSI datasets is briefly presented.

EPFL2022

A single epidermal stem cell strategy for safe ex vivo gene therapy

Graham Knott, Jacques Rougemont, Yann Barrandon, Ariane Rochat, Andrea Zaffalon, Nicolas Grasset, Stéphanie Danièle Hélène Droz-Georget, Sara Benmohammed, Emmanuelle Savioz-Dayer, Alessandra Recchia

There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy.

Wiley Open Access2015

Advanced metabolite mapping at ultra-high field using 1H-MRS, 1H-MRSI and macromolecules: applications in a rat model of type C hepatic encephalopathy

Dunja Simicic

EPFL2022

A single epidermal stem cell strategy for safe ex vivo gene therapy

Wiley Open Access2015