L'utilisation des cellules souches dans l'étude et le traitement des maladies du foie

 

Massimiliano Paganelli

Centre de recherche du CHU Sainte-Justine

 

Domaine :  santé de la mère, des enfants et des adolescents

Programme chercheurs-boursiers-cliniciens  - Junior 1

Concours 2017-2018

One in ten Canadians is affected by liver disease. The standard of care for acute and chronic liver failure (the common outcome of any progressive liver disease), as for most inborn errors of liver metabolism, is liver transplantation. Unfortunately, only 400 transplants are performed each year in Canada, for over 5000 deaths/year secondary to liver disease. My research aims at developing innovative stem cell-based therapies to restore the lacking liver functions in children and adults with liver disease. In my laboratory, we obtain stem cells (called induced pluripotent stem cells, or iPSCs) from small blood samples of patients and healthy subjects, and use them to generate liver cells (the hepatocytes) and 3D livers-in-a-dish ("organoids"). Such hepatocytes and organoids are employed to model liver diseases in order to advance our knowledge and test new drugs. We are assessing the feasibility of using iPSC-derived hepatocytes to treat inborn errors of liver metabolism (rare conditions caused by a gene mutation entailing multiple severe and often lethal consequences).

We plan to generate hepatocytes from patient-derived iPSCs in which the DNA mutation causing the disease will be previously corrected. Such "healthy" liver cells will be injected back to the patient ("autologous" cell transplantation), thus curing the disease while freeing the patient from the need of liver transplantation, lifelong treatments and compelling diets. We will test such an approach in a murine model of hereditary tyrosinemia type I (a severe condition being particularly frequent in Quebec) as a demonstration in principle, and then extend the results to other metabolic liver diseases. Furthermore, we are using our liver organoids to develop a pioneering stem cell-derived product to restore the lacking liver functions in patients with acute and chronic liver failure, thus preventing/treating the complications and improving survival without the need of liver transplantation or lifelong treatments.