226 research outputs found
Students' perceptions of the nature of evolutionary theory
No full textThis study explored how some college students understand the nature of the theory of evolution and how they evaluate its scientific status. We conducted semistructured interviews with 15 college biology seniors in which we asked them to explain why they think evolution assumes the status of a scientific theory, how it compares to other scientific theories, and what criteria do they use to determine if an explanation is scientific or not. Students' responses encompassed five themes that include evidence, certainty, experimentation, method of theory generation, and prediction. Those themes focused on the theory's empirical dimension which seemed to be derived from a generic and simplistic model of physical science theories that valued direct evidence. Demanding that evolutionary theory conform to this model reveals a misunderstanding of its nature. This misunderstanding was expressed in relation to aspects of methodology, explanation, and prediction. The findings underscore the need for using explicit discipline- and context-specific approaches to teaching and learning about scientific theories. © 2005 Wiley Periodicals, Inc.Abd-El-Khalick F., 2001, J SCI TEACHER ED, V12, P215, DOI DOI 10.1023-A:1016720417219; Abd-El-Khalick F, 2000, INT J SCI EDUC, V22, P665, DOI 10.1080-09500690050044044; Abd-El-Khalick F, 2000, J RES SCI TEACH, V37, P1057, DOI 10.1002-1098-2736(200012)37:101057::AID-TEA33.0.CO;2-C; ALEIXANDRE MJ, 1992, INT J SCI ED, V14, P51; American Association for the Advancement of Science, 1990, SCI ALL AM; Anderson DL, 2002, J RES SCI TEACH, V39, P952, DOI 10.1002-tea.10053; Bartholomew H, 2004, SCI EDUC, V88, P655, DOI 10.1002-sce.10136; BISHOP BA, 1990, J RES SCI TEACH, V27, P415, DOI 10.1002-tea.3660270503; Brem SK, 2003, SCI EDUC, V87, P181, DOI 10.1002-sce.10105; Brickhouse N. W., 2002, SCI ED, V11, P573, DOI 10.1023-A:1019693819079; Cartwright N., 1983, HOW LAWS PHYS LIE; CLOUGH M, 1995, AM BIOL TEACH, V5, P401; Dagher ZR, 2004, INT J SCI EDUC, V26, P735, DOI 10.1080-0950069032000138806; Dagher ZR, 1997, J RES SCI TEACH, V34, P429, DOI 10.1002-(SICI)1098-2736(199705)34:5429::AID-TEA23.0.CO;2-S; Driver R., 1996, YOUNG PEOPLES IMAGES; Duschl R. A., 1990, RESTRUCTURING SCI ED; Elgin M, 2003, PHILOS SCI, V70, P1380, DOI 10.1086-377415; Ferrari M, 1998, INT J SCI EDUC, V20, P1231, DOI 10.1080-0950069980201005; Fysh R., 1998, RES SCI EDUC, V28, P399, DOI 10.1007-BF02461507; Ghiselin Michael T., 1997, METAPHYSICS ORIGIN S; GIBBS A, 1992, AM BIOL TEACH, V54, P137; DEMASTES SS, 1995, SCI EDUC, V79, P637, DOI 10.1002-sce.3730790605; Griffiths A. K., 1995, SCH SCI MATH, V95, P248, DOI DOI 10.1111-J.1949-8594.1995.TB15775.X; JACKSON D, 1995, J RES SCI TEACH, V34, P93; Khishfe R, 2002, J RES SCI TEACH, V39, P551, DOI 10.1002-tea.10036; Leach J, 2003, SCI EDUC, V87, P831, DOI 10.1002-sce.10072; Lemke J. L, 1990, TALKING SCI; Mahner M., 1997, FDN BIOPHILOSOPHY; Matthews M., 2000, TIME SCI ED TEACHING; Mayr E., 1982, GROWTH BIOL THOUGHT; Mayr E., 2001, WHAT EVOLUTION IS; MCCOMAS W, 1909, NATURE SCI SCI ED RA, P3; McComas W. F., 1998, NATURE SCI SCI ED RA, P41; Meyling H., 1997, SCI EDUC, V6, P397, DOI 10.1023-A:1017908916810; National Academy of Sciences, 1998, TEACH EV NAT SCI; National Research Council, 1996, NAT SCI ED STAND; NORRIS S, 1995, J RES SCI TEACH, V22, P817; Osborne J, 2003, J RES SCI TEACH, V40, P692, DOI 10.1002-tea.10105; Passmore C, 2002, J RES SCI TEACH, V39, P185, DOI 10.1002-tea.10020; Root-Bernstein R., 1984, P64; Rose Steven, 1998, LIFELINES BIOL DETER; Roth WM, 1997, J RES SCI TEACH, V34, P145, DOI 10.1002-(SICI)1098-2736(199702)34:2145::AID-TEA43.0.CO;2-T; Rudolph JL, 2000, J CURRICULUM STUD, V32, P403, DOI 10.1080-002202700182628; Ruse M., 1988, PHILOS BIOL TODAY; RYAN AG, 1992, SCI EDUC, V76, P559, DOI 10.1002-sce.3730760602; Sandoval WA, 2003, J RES SCI TEACH, V40, P369, DOI 10.1002-tea.10081; Schwab J. J., 1962, TEACHING SCI, P1; Shipman HL, 2002, SCI EDUC, V86, P526, DOI 10.1002-sce.10029; Sinatra GM, 2003, J RES SCI TEACH, V40, P510, DOI 10.1002-tea.10087; Sober E., 1993, PHILOS BIOL; SOLOMON J, 1992, J RES SCI TEACH, V29, P409, DOI 10.1002-tea.3660290408; Stewart J, 2001, SCI EDUC, V85, P207, DOI 10.1002-sce.1006; Strauss A. L., 1987, QUALITATIVE ANAL SOC34323
Long-term Outcomes of Combined Endoscopic-Radiological Approach for the Management of Complete Transection of the Biliary Tract
No full textComplete transection of the main bile duct (CTMD) is a major complication during hepato-bilio-pancreatic (HBP) surgery and is associated with high morbidity and mortality. In recent years, a combined endoscopic-radiological approach (CERA) for minimally invasive treatment of CTMD has been introduced, but evidence on its long-term outcomes is limited. Our aim is to report efficacy, safety, and long-term outcomes of CERA for the management of post-surgical CTMD in a tertiary referral center
Single-port sleeve gastrectomy: a comparison between transumbilical and left hypochondrium approaches
No full textBackground: Left hypochondrium (LHC) approach has been routinely used in our department for performing single-port sleeve gastrectomy (SPSG). Starting from 2019, a transumbilical approach (TU) has been adopted in selected patients. The aim of this study was to report and compare our results of both approaches (LHC and TU) with special focus on incisional hernia (IH).
Methods: The data of patients who underwent sleeve gastrectomy via both approaches between 2019 and 2022 were retrospectively analyzed. An assessment of IH rate was carried out by reviewing abdominal computed tomography scans performed one year after surgery.
Results: During the study period, 449 patients who underwent SPSG were included in the final analyze. Patients in the TU group (n = 136, 30%) were more frequently female with a lower BMI and fewer comorbidities. An umbilical hernia was observed in 60% of patients in the TU group. Operative duration was longer in the LHC group (80 min vs. 64 min, P < 0.0001). Early complications rates did not differ between the groups (1.9% LHC vs. 0.7% TU, P = 0.353). During follow-up, 65 patients (14%) developed an IH: 9.9% and 25% in the LHC and TU groups, respectively (P < 0.0001). Weight loss and comorbidities resolution at 1 year were globally similar between the two groups.
Conclusion: We have demonstrated the feasibility, safety, and efficacy of SPSG via both LHC and TU approaches. The advantage of the LHC approach is its routine applicability. The TU approach offers an esthetic advantage and a shorter operative time but is associated with a much higher IH rate
Liver regeneration : stimulus for hepatocyte transplantation
No full textLe foie a des capacités de régénérations importantes qui lui permettent de reconstituer progressivement sa masse cellulaire suite à une agression. L’induction d’une régénération hépatique est une approche qui a été utilisée dans de nombreux modèles animaux afin de favoriser la prise de greffe hépatocytaire pour le traitement des maladies métaboliques héréditaires hépatiques (MMHH). Par ailleurs, les capacités de régénération du foie sont utilisées en pratique clinique courante dans le cadre de la chirurgie hépatique afin de préparer le foie à une hépatectomie majeure. Les principaux objectifs de ce travail ont été d’étudier des moyens peu invasifs pour induire une importante régénération hépatique dans deux buts précis : i) favoriser la transplantation d’hépatocytes thérapeutiques pour le traitement des MMHH ; ii) élargir les possibilités de prise en charge des patients nécessitant une hépatectomie.Dans un premier temps, nous avons évalué l’effet d’une embolisation portale partielle (EPP) au cours de la transplantation d’hépatocytes dans un des modèles animaux de l’hypercholestérolémie familiale de type IIA, le lapin Watanabe. Dans un deuxième temps, nous avons mis au point chez le rat, une technique d’EPP résorbable répétée visant à entrainer un stimulus répété de régénération hépatocytaire afin d’envisager par la suite l’utilisation de cette technique avant transplantation d’hépatocytes. En parallèle de ces travaux fondamentaux, nous avons évalué en approche clinique l’intérêt de l’EPP résorbable avant hépatectomie majeure. Nos travaux dans le modèle du lapin Watanabe ont montré la faisabilité du protocole, une correction phénotypique in vitro, une amélioration de la prise de greffe hépatocytaire et une expression prolongée du transgène. Notre équipe a développé chez le rat un stimulus additionnel de prolifération hépatocytaire qui permet une augmentation du poids et du volume du foie non embolisé en comparaison à une seule EPP résorbable. Enfin, dans une série rétrospective préliminaire, la technique d’EPP résorbable a été utilisée avant hépatectomie majeure. L’approche a été bien tolérée chez tous les patients et a permis de systématiquement envisager la chirurgie.L’EPP résorbable est une technique peu invasive capable d’induire une régénérative hépatique efficace. Cette approche pourrait permettre notamment d’augmenter les capacités de proliférations hépatiques par la répétition du stimulus d’embolisation. A terme, l’EPP résorbable répétée pourrait permettre de modeler à la demande l’organisation du volume hépatique favorisant ainsi l’hypertrophie de tel ou tel secteur en fonction des besoins.The liver has an important regenerative capacity allowing progressive reconstitution of the hepatic volume after an aggression. The induction of liver regeneration was used in different animal models in order to increase engraftment during hepatocyte transplantation for the treatment of inherited metabolic liver diseases (IMLD). Furthermore, liver regenerative capacities are used in routine clinical practice before liver surgery in order to prepare the liver for major hepatectomy.The main objective of this doctoral thesis was to evaluate minimally invasive approaches inducing substantial liver regeneration, focusing in two specific aims: i) increasing the engraftment of therapeutic cells for the treatment of IMLD; ii) expanding the therapeutic options for patients requiring an hepatectomy In a first study, we evaluated the impact of a partial portal vein embolization (PVE) during hepatocyte transplantation in the animal model of familial hypercholesterolemia type IIA, the Watanabe rabbit. In a second investigation, we developed an approach of repeated reversible PVE in a rat model to further boost liver hypertrophy, planning to apply this approach in hepatocyte transplantation. In parallel, we evaluated the clinical interest of reversible PVE before major hepatectomy.Our results of PVE during hepatocyte transplantation in the Watanabe rabbit model demonstrated the feasibility of the procedure, in vivo phenotypic correction, increase of liver cell engraftment and stable transgene expression. Our team developed in the rat an additional stimulus of hepatocyte proliferation allowing increase of non-embolized liver lobe weight and volume in comparison to a single reversible PVE. Finally, the reversible PVE approach was evaluated before major hepatectomy in a preliminary retrospective series of 20 patients. The procedure was well tolerated and allowed to plan surgery in all patients.Reversible PVE is a minimally invasive technique allowing to successfully induce liver regeneration. This approach could increase hepatocyte proliferation capacity by using an additional stimulus of repeated embolization. In the future, reversible PVE may allow on demand modeling of liver volumes organization by supporting the hypertrophy of a specific liver lobe when required
Transplantation of genetically modified hepatocytes : liver regeneration and approaches for improving hepatocyte engraftment
No full textLa transplantation d’hépatocytes est un procédé séduisant pour remplacer les cellules déficientes dans un foie anatomiquement normal. Dans les maladies métaboliques héréditaires hépatiques (MMHH), la thérapie cellulaire présente un potentiel espoir thérapeutique. Le remplacement d'un pourcentage restreint (5-10%) d’hépatocytes déficients par des hépatocytes normaux pourrait rétablir durablement la fonction métabolique. Les résultats des essais cliniques de transplantation d'hépatocytes génétiquement modifiés ou non sont moins concluants, montrent une prise de greffe insuffisante et, dans la plupart des études, un effet thérapeutique transitoire. L’efficacité limitée de la transplantation d’hépatocytes isolés dans le traitement des MMHH semble en partie liée au faible pourcentage de la masse hépatocytaire reconstituée par les hépatocytes définitivement greffés et fonctionnels. De nombreux modèles animaux ont été développés pour étudier les facteurs pouvant augmenter le nombre et le pourcentage d’hépatocytes transplantés et greffés. Cependant, la majorité de ces modèles ne sont pas transposables en clinique car ils présentent des risques importants ou mal évalués pour les patients. Les principaux objectifs de ce travail ont été d’étudier des moyens peu invasifs pour induire une régénération hépatique et une prise de greffe hépatocytaire significatives dans le but de développer une nouvelle approche de transplantation d’hépatocytes génétiquement modifiés ex vivo pour le traitement de l’hypercholestérolémie familiale. L’effet d’une embolisation portale partielle (EPP) réversible sur la prolifération hépatocytaire et la régénération hépatique a été évalué chez le macaque. A la différence de l’EPP par un produit non résorbable, il ne s’agit pas d’une approche potentiellement délétère à long terme. Une obstruction veineuse plus complète a été provoquée en utilisant le Curaspon®, une gélatine biodégradable, en forme de poudre. Nous avons démontré pour la première fois dans la littérature l’efficacité d’une EPP réversible à induire une importante prolifération hépatocytaire et régénération hépatique. Nos données suggèrent qu’une occlusion portale initiale et temporaire est suffisante pour déclencher les mécanismes responsables d’une régénération hépatique dans le foie non-embolisé. L’utilisation du Curaspon® en poudre peut être considérée comme la forme la plus évoluée d’EPP : très distale, résorbable, qui dure suffisamment pour induire l’hypertrophie hépatique. Cette technique pourrait être indiquée dans des situations cliniques nécessitant une régénération hépatique de courte durée (ex. le traitement des cancers du foie en plusieurs étapes) ou dans des cas qui ne nécessitent pas une résection hépatique, comme la transplantation d’hépatocytes pour le traitement de MMHH. Ces résultats nous ont permis d’évaluer cette approche dans notre protocole préclinique de thérapie génique pour le traitement de l’hypercholestérolémie familiale chez le primate, par autotransplantation d’hépatocytes génétiquement modifiés ex vivo par un vecteur lentiviral. Nous avons démontré que l’EPP réversible induit une régénération hépatique du foie non-embolisé et améliore notablement les résultats de la transplantation d’hépatocytes isolés génétiquement modifiés exprimant la GFP. Seize semaines après la transplantation, les hépatocytes transduits et greffés exprimaient le transgène contrôlé par le promoteur apo-AII humain. Notre protocole a montré pour la première fois chez un gros animal que l’EPP par un produit résorbable entraine avec des conditions de sécurité optimales une repopulation hépatique importante par des hépatocytes transduits par un vecteur lentiviral, et ceci même à distance de la transplantation hépatocytaire. Les résultats encourageants de ces travaux nous ont ouvert la voie pour avancer sur notre projet préclinique et envisager la réalisation d’une étude clinique de phase I/II pour le traitement de l’hypercholestérolémie familiale.Hepatocyte transplantation is an attractive process for replacing deficient cells in an anatomically normal liver. In metabolic liver diseases, cell therapy could be an interesting alternative to orthotopic liver transplantation. The replacement of a small percentage (5-10%) of deficient hepatocytes by normal hepatocytes could restore the metabolic defect at a long term. Data from clinical studies of hepatocyte autotransplantation or allotransplantation, genetically modified or not, provided poor results, insufficient cell engraftment in the liver parenchyma and, in the majority of cases, a transient therapeutic effect. The limited efficacy of hepatocyte transplantation in metabolic liver diseases is mainly due to the poor percentage of engrafted and finally functional hepatocytes. Numerous animal models have been developed in order to study the factors that could increase the number and the percentage of transplanted and engrafted hepatocytes. However, the majority of these models cannot be used in patients since they present important risks for them. The aim of this work was to evaluate less invasive procedures for inducing liver regeneration and significant hepatocyte engraftment in order to develop a new approach of transplantation of ex vivo genetically modified hepatocytes for the treatment of familial hypercholesterolemia. The effect of reversible portal vein embolization (PVE) on liver regeneration and hepatocyte proleferation was evaluated in monkeys. In contrast to PVE by a permanent embolizing agent, reversible PVE has not a long term deleterious effect on embolized liver. A more complete venous occlusion was obtained by using the powdered form of an absorbable gelatin sponge (Curaspon®). We showed for the first time in the literature the safe and successful use of reversible PVE for inducing significant hepatocyte proliferation and liver regeneration. Our data support that an initial occlusion of the portal branch, even if not permanent, is sufficient to start the mechanisms of liver regeneration in the contralateral lobe. Embolization with Curaspon® powder could be considered to be the ultimate form of embolization: very distal, reversible and lasting sufficiently in order to induce substantial liver hypertrophy. Our findings suggest that this method could reliably be used for clinical purposes, particularly in situations in which short-term regeneration is required (i.e. multi-step management of hepatic malignancies) or in cases where resection of the liver is not finally necessary, such as in hepatocyte transplantation for the treatment of metabolic liver diseases. These promising results on reversible PVE allowed us to evaluate this approach in our preclinical study of gene therapy for the treatment of familial hypercholesterolemia in macaques. Our protocol consisted of an autotransplantation of ex vivo genetically modified hepatocytes by a lentiviral vector. We showed that reversible PVE induces liver regeneration of the non-embolized liver segments and improves considerably hepatocyte transplantation of genetically modified cells expressing Green Fluorescent Protein (GFP). Sixteen weeks after transplantation, transduced engrafted hepatocytes expressed the transgene, which was under control of the human apo-AII promoter. Our protocol showed for the first time in a big animal that PVE by an absorbable agent leads safely to an important and long-term repopulation of the liver by lentivirally transduced hepatocytes. The extremely encouraging results of this work opened our way advancing in our preclinical study and preparing a phase I/II clinical trial for the treatment of familial hypercholesterolemia based on our protocol of autotransplantation of ex vivo genetically modified hepatocytes by a lentiviral vector
Computed tomography assessment of postoperative gastric vascular supply and staple-line leak development after sleeve gastrectomy
No full textBackground: Residual arterial supply of the gastric tube after sleeve gastrectomy (SG) can be damaged by surgery, which can reduce gastric tube perfusion and could promote postoperative leakage. Objective: To compare the postoperative vascularization of the gastric tube using early computed tomography (CT) scanning after SG in patients with or without postoperative staple-line leak. Setting: University hospital. Methods: A retrospective analysis of a prospective database was performed in consecutive patients undergoing SG. Patients who presented with a staple-line leak were matched (1:3) with a control group of patients who underwent surgery without postoperative morbidity during the same period. Gastric tube vascularization was studied on a postoperative day 2 CT scan in both groups of patients. Results: During the study period, 1826 patients underwent SG, including 42 patients (2.3%) who presented with a staple-line leak. Those 42 patients were successfully matched to 126 control patients. Global identification of residual gastric arterial supply in early postoperative CT scans was similar in patients with or without staple-line leak after SG. However, residual vascular supply of the gastroesophageal junction (i.e., terminal and anterior cardiotuberosity branches of the left gastric artery or left inferior phrenic artery) was more frequently interrupted by the staple line in the group of patients who developed a gastric leak. Conclusion: This study suggests a correlation between interruption of the main arteries supplying the gastroesophageal junction by the staple line on early postoperative CT scans and the development of gastric leak after SG. These results support the vascular theory as one of the causes of leak after SG
Total pancreatectomy for pancreatic carcinoma. when, why, and what are the outcomes? Results of a systematic review
No full textThe role of total pancreatectomy (TP) to treat pancreatic carcinoma is still debated. The aims of this study were to systematically review the previous literature and to summarize the indications and results of TP for pancreatic carcinoma. A systematic search was performed to identify all studies published up to November 2018 analyzing the survival of patients undergoing TP for pancreatic carcinoma. Clinical effectiveness was synthetized through a narrative review with full tabulation of results. Six studies published between 2009 and 2016 were retrieved, including 316 patients. The major indication was positive pancreatic margin at frozen section during partial pancreatectomy. The overall morbidity ranged from 36% to 69%, and mortality from 0% to 27%. Overall survival ranged from 52.7% to 67% at 1 year, from 20% to 42% at 3 years of follow-up, whereas the 5-year estimated overall survival ranged from 4.5% to 21.9%. Total pancreatectomy has an important role in the armamentarium of pancreatic surgeons. Postoperative morbidity and mortality are not negligible, but a trend for better postoperative outcomes in recent years is noticed. Mortality related to difficult glycemic control is rare. Long-term survival is comparable with survival after partial pancreatectomy for carcinoma
Seismic strengthening of bond-critical regions in rectangular reinforced concrete columns using fiber-reinforced polymer wraps
No full textThe use of external fiber-reinforced polymer (FRP) wraps for bond strengthening of spliced reinforcement in rectangular reinforced concrete (RC) columns and the consequent effect on the seismic response of the columns are experimentally investigated. Fullscale-unconfined and FRP-confined column specimens with lap-spliced reinforcement at the base were tested Also, companion columns with continuous reinforcement and with internal steel confinement to satisfy the ACI building code requirements for regions of high seismic hazard (earthquake-resistant columns) were tested for comparison. It was found that confining the spliced zone with FRP wraps increased the bond strength of the spliced bars, reduced the bond deterioration and pinching under cyclic loading, and increased the lateral load resistance and ductility of the columns. The corresponding improvements approached those of the earthquake-resistant columns. The lateral strain developed in the FRP increased with decreasing ratio of concrete cover to splice diameter and with increasing area of FRP wraps. The predictions of bond strength of spliced bars in FRP-confined concrete using available design expressions were in good agreement with the test data. © 2008, American Concrete Institute. All rights reserved.ACI Committee, 2002, 31802 ACI; ACI Committee 440, 2002, 4402R02 ACI; *ACI INN TASK GROU, 1999, ITGT1199 ACI; Darwin D, 2005, ACI STRUCT J, V102, P892; Harajli MH, 2005, J COMPOS CONSTR, V9, P4, DOI 10.1061-(ASCE)1090-0268(2005)9:1(4); HARAJLI MH, 2005, FIBER REINFORCED POL, P579; Harajli MH, 2004, ACI STRUCT J, V101, P47; Harries KA, 2006, ACI STRUCT J, V103, P874; ORANGUN CO, 1975, 1543F1975 U TEX AUST; Sause R, 2004, ACI STRUCT J, V101, P708; Seible F, 1997, J COMPOS CONSTR, V1, P52, DOI 10.1061-(ASCE)1090-0268(1997)1:2(52); Sheikh SA, 2002, ACI STRUCT J, V99, P72; Zuo J, 2000, ACI STRUCT J, V97, P63023212
Response: "Conversion During Laparoscopic Liver Resections: a Step Forward"
No full textOperations should be then broken down in steps (i.e. trocar position, preparation of Pringle maneuver, intraoperative ultrasound, mobilization of the liver, pedicle dissection, hepatic veins exposure...) and reviewed with the proctor multiple times in order to speed up the learning process and facilitate the approach to the technique. Every laparoscopic liver resection is in fact made up of different steps each having potential pitfalls; the difficulty of accurately stage the disease through the intraoperative ultrasound, the challenges of managing potential bleeding and the different view during liver mobilization are only examples of what a surgeon has to get through during a laparoscopic resection of the liver
Repeated resorbable portal vein embolization : stimulating liver regeneration
No full textLe foie possède une capacité de régénération importante qui lui permet de reconstituer son volume suite à une agression. L’induction d’une régénération hépatique est réalisée en pratique courante en chirurgie hépatique afin de préparer le foie à une hépatectomie majeure. Elle est également utilisée dans de nombreux modèles animaux afin de favoriser la prise de greffe hépatocytaire au cours de la transplantation d’hépatocytes pour le traitement de maladies métaboliques héréditaires hépatiques. Les principaux objectifs de ce travail ont été d’étudier une méthode peu invasive pour induire une importante régénération hépatique : d’une part pour élargir les possibilités de prise en charge des patients nécessitant une hépatectomie, et d’autre part pour favoriser la prise de greffe des hépatocytes transplantés pour le traitement des maladies métaboliques héréditaires hépatiques.Dans un premier temps, nous avons mis au point chez le rat une technique d’embolisation portale partielle résorbable répétée (EPPRR) visant à entrainer un stimulus additionnel de régénération hépatique. Ces travaux ont validé le concept de la méthode d’EPPRR en montrant une augmentation de la prolifération hépatocytaire et une hypertrophie dans la partie du foie non embolisée.Ce protocole d’EPPRR a ensuite été appliqué dans un modèle préclinique de gros animal. Nous avons étudié chez le porc les conséquences de l’EPPRR et montré que cette technique était reproductible, bien tolérée, et qu’elle permettait une hypertrophie de la partie du foie non embolisée.Parallèlement, nous avons appliqué l’EPPRR avant transplantation d’hépatocytes chez le rat. A partir du foie de rats transgéniques exprimant la GFP (green fluorescent protein), nous avons pu isoler des hépatocytes GFP+. Ces cellules ont été transplantées dans le foie de rats receveurs GFP- en association avec une EPPRR. Nous avons montré que le stimulus de régénération répété provoqué par l’EPPRR permettait une augmentation de la prise de greffe.En conclusion, l’EPPRR est une technique peu invasive capable d’induire une régénérative hépatique efficace. Cette approche pourrait jouer un rôle dans la prise en charge des tumeurs hépatique et l’optimisation de la transplantation d’hépatocytes pour le traitement des maladies métaboliques héréditaires hépatiques.The liver has an important regenerative capacity allowing reconstitution of the hepatic volume after an aggression. The induction of liver regeneration is used in routine clinical practice before liver surgery in order to prepare the liver for major hepatectomy. It is also used in numerous animal models in order to increase hepatocyte engraftment during hepatocyte transplantation for the treatment of inherited metabolic liver diseases. The main objective of this work was to evaluate a minimally invasive approach to induce substantial liver regeneration: firstly, to expand the therapeutic options for patients requiring an hepatectomy, and secondly to increase the engraftment of transplanted hepatocytes for the treatment of inherited metabolic liver diseases.In a first study, we developed in the rat model a technique of repeated reversible portal vein embolization (RRPVE) to induce an additional stimulus of liver regeneration. This study established the proof of concept of the RRPVE method, showing an increase in hepatocyte proliferation and hypertrophy in the non-embolized liver.This RRPVE protocol was then used in a preclinical model of large animal. We studied in swine the consequences of the RRPVE and showed that the procedure was reproducible, well tolerated, and allowed hypertrophy of the non-embolized liver.In parallel, we applied RRPVE before hepatocyte transplantation in the rat model. From the liver of transgenic rats expressing GFP (green fluorescent protein), we were able to isolate GFP+ hepatocytes. These cells were transplanted in the liver of recipient GFP- rats in association with RRPVE. We demonstrated that the repetition of the regeneration stimulus induced by RRPVE allowed increased hepatocyte engraftment.In conclusion, RRPVE is a minimally invasive technique able to induce efficient liver regeneration. This approach could play a part in the management of hepatic malignancies and the optimization of hepatocyte transplantation in the treatment of inherited metabolic liver diseases
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