CryOrg

Chronic liver diseases affect more than 500 million people worldwide. Liver transplantation is the only treatment for severe diseases, but it is limited to a small number of patients due to the shortage of organs. The implantation of bioengineered liver tissue represents a major hope. To this end, it is necessary to propose an efficient strategy for the production and freezing of tissue-engineered products that can be rapidly available at the patient's bed. We have gathered several internationally renowned academic and industrial partners with a high level of expertise in complementary fields (liver biology, human induced pluripotent stem cells (hiPSCs), organoids, encapsulation in biomaterials, and cryopreservation) to address this multidisciplinary challenge. We propose to develop protocols to freeze and thaw encapsulated organoids formed from hepatocytes, mesenchymal stem cells, and endothelial cells all derived from hiPSCs. Their cryopreservation being the major issue of this project. Different processes have already been identified and will be evaluated. Encapsulation in porous alginate beads will ensure the protection of the organoids during these phases and will facilitate future implantation in the patient. Different cellular functions will be studied in vitro during all production steps and evaluated in a preclinical mouse model. This is the first time that a project integrates all these innovations to meet the healthcare needs of the 21st century in liver regenerative medicine. Indeed, the development of cryopreservation is necessary to allow a complete characterisation of the different batches (safety/efficacy) while ensuring the rapid availability of functional and implantable encapsulated organoids in the liver.