Centre de Recherche du\u00a0CHU Ste-Justine m.paganelli@umontreal.ca<\/a><\/p>\n L\u2019objectif ultime de notre recherche est le traitement des maladies du\u00a0foie par le moyen de la th\u00e9rapie\u00a0cellulaire. Au laboratoire nous g\u00e9n\u00e9rons les\u00a0cellules souches pluripotentes induites (iPS) \u00e0 partir du sang des patients\u00a0avec\u00a0maladie h\u00e9patique, dans le but de les utiliser pour:<\/p>\n 1.\u00a0 \u00a0\u00a0\u00a0Diff\u00e9renciation\u00a0en h\u00e9patocytes\u00a0et cr\u00e9ation des mod\u00e8les\u00a0in vitro des maladies. Ces mod\u00e8les son pr\u00e9cieux pour\u00a0\u00e9tudier la\u00a0physiopathologie, essayer des nouveaux traitements, et tester\u00a0l\u2019effet des traitements\u00a0d\u00e9j\u00e0 connus avant de les administrer au patient donneur\u00a0des cellules (dans le but d\u2019une m\u00e9dicine\u00a0personnalis\u00e9e). Research in the lab aims\u00a0at treating liver diseases by the means of cellular therapy. We generate\u00a0induced pluripotent stem (iPS) cells\u00a0from the blood of patients with liver\u00a0diseases in order to achieve the following objectives:<\/p>\n 1.\u00a0In vitro\u00a0differentiation to hepatocyte-like cells\u00a0and establishment of cellular models of the different diseases.\u00a0Such\u00a0models are used to study the pathophysiology of the disease, try new\u00a0treatments, and assess the effect of\u00a0known drugs in order to predict\u00a0in vivo\u00a0responses (personalized\u00a0medicine).<\/p>\n 2.\u00a0Genome editing to\u00a0correct the disease-causing mutation (for inborn errors of liver\u00a0metabolism), with subsequent expansion of the corrected population,\u00a0differentiation to hepatocyte-like cells\u00a0and transplantation. Such an\u00a0approach aims at restoring the deficient function eliminating the need for\u00a0liver\u00a0transplantation.<\/p>\n 3.\u00a0Generation of liver organoids with tridimensional\u00a0structure and function comparable to the human liver. Such\u00a0liver buds will\u00a0be created from corrected iPS obtained from patients with metabolic liver\u00a0disease. Once their\u00a0creation protocol and culture conditions improved and\u00a0their safety proven, liver organoids might be\u00a0transplanted to patients to\u00a0replace their diseased liver.<\/p>\n The projects currently ongoing\u00a0in the lab imply the study of iPS cells-to-hepatocyte differentiation process,\u00a0the creation and validation of an in\u00a0vitro\u00a0model of hereditary tyrosinemia type I, the correction of the\u00a0disease-causing mutation in\u00a0such a model, and the assessment of the efficacy and\u00a0safety of the transplantation of hepatocytes derived form corrected\u00a0iPS cells\u00a0in a murine model of tyrosinemia.<\/p>\n<\/div>\n Coordonn\u00e9es Centre de Recherche du\u00a0CHU Ste-Justine 3175, Chemin de la C\u00f4te-Sainte-Catherine Montr\u00e9al (Qu\u00e9bec) – H3T 1C5 T 514 345-4931, poste 4278 F 514 345-4999 m.paganelli@umontreal.ca Consultez le site web institutionnel […]<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":3557,"menu_order":0,"comment_status":"closed","ping_status":"open","template":"","meta":{"footnotes":""},"class_list":["post-4156","page","type-page","status-publish","hentry"],"yoast_head":"\n
\n3175, Chemin de la C\u00f4te-Sainte-Catherine
\nMontr\u00e9al (Qu\u00e9bec) – H3T 1C5
\nT<\/strong> 514 345-4931, poste 4278
\nF<\/strong> 514 345-4999<\/p>\nAxes de recherche<\/h2>\n
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Description de la recherche<\/h2>\n
\n2.\u00a0 \u00a0\u00a0\u00a0Pour les maladies m\u00e9taboliques du foie, correction\u00a0de la mutation causant la maladie, expansion de la\u00a0population\u00a0corrig\u00e9e, diff\u00e9renciation en h\u00e9patocytes et transplantation chez le\u00a0patient. Cette technique vise \u00e0 corriger la\u00a0d\u00e9ficience enzymatique causant la\u00a0maladie par th\u00e9rapie cellulaire autologue, en \u00e9liminant la n\u00e9cessit\u00e9 de la\u00a0transplantation h\u00e9patique et la d\u00e9pendance de l\u2019immunosuppression.
\n3.\u00a0 \u00a0\u00a0\u00a0G\u00e9n\u00e9ration\u00a0d\u2019organo\u00efds h\u00e9patiques avec structure tridimensionnelle et fonction comparable\u00a0au foie humain.\u00a0Ces bourgeons h\u00e9patiques seront cr\u00e9\u00e9s \u00e0 partir des cellules iPS\u00a0corrig\u00e9es des patients avec maladie\u00a0m\u00e9tabolique. Une fois am\u00e9lior\u00e9e la\u00a0technologie de cr\u00e9ation et les condition de culture, et prouv\u00e9 leur\u00a0s\u00e9curit\u00e9, ces\u00a0organo\u00efds pourront \u00eatre transplant\u00e9s chez les patients pour remplacer leur foie\u00a0malade.
\nLes projets en cours au laboratoire impliquent l\u2019\u00e9tude\u00a0in vitro\u00a0de\u00a0tyrosin\u00e9mie de type I, la correction de la mutation causant cette maladie,\u00a0et\u00a0l\u2019\u00e9valuation de l\u2019efficacit\u00e9 et s\u00e9curit\u00e9 de la transplantation des h\u00e9patocytes\u00a0d\u00e9riv\u00e9s des cellules iPS corrig\u00e9es dans un\u00a0mod\u00e8le murin de tyrosin\u00e9mie.<\/p>\n<\/div>\nResearch axis<\/h2>\n
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Research description<\/h2>\n
Consultez le site web institutionnel du chercheur<\/a><\/h3>\n