Greffe de cellules par la veine porteMicrocapsules made of biosynthetic hydrogel scaffolds for intravascular liver tissue regeneration Therapy (Présenté en français)

Introduction: The liver is the natural microenvironment for hepatocytes transplantation but unfortunately engraftment efficiency is low. We have developed hydrogel scaffolds that can be used for intra-hepatic or intravascular injection. They are made of fibrinogen crosslinked with polyethylene glycol (PEG-Fib) - diacrylates side chains, that form a hydrogel when mixed with cells and exposed to UV light. The hydrogel scaffolds may reduce shear stress and immediate immunological pressure after intravascular injection and thus may improve engraftment. Aims: Assessment of intraportal transplantation of PEG-Fib microcapsules with HuH7 cells and adult hepatocytes.Methods: Development of the model of intravascular transplantation of encapsulated cells. Assessment of encapsulated cell viability (PI/FDA). Comparing engraftment efficiency of encapsulated and non-encapsulated cells in rat model in-vivo using semiquantitative PCR (human 16q23.1) or real time qPCR (rat SRY-gene) and histology.Results: HuH-7 cell-polymer constructs were transplanted to the liver, spleen and sub cutis allowing cells to proliferate for two weeks. The viability of cells immediately after preparation of microcapsules was 70%. Microcapsules cell constructs at a size of 200-700 mm comprising HuH-7 or adult hepatocytes have been successfully injected into portal vein and transplanted cells were shown at 24h, 72h and 168h after procedure by histology and PCR. When adult hepatocytes viability was compared with and without the polymer we found early loss of cells but very good long term survival.Conclusions: The cells within the constructs after intraportal transplantation were viable for a week. This is an important method for the development of intravascular liver tissue engineering.Intervenant : Dominique FRANCO