Bio-engineering functional liver tissue from human biomatrix and liver stem cells: The Matrix Reloaded!

Project summary

The aim of this project is to develop a closed loop perfusion platform to construct functional liver tissue by repopulation of human liver extracellular matrix scaffolds (biomatrix) with patient-specific liver stem cells: The Matrix Reloaded. To develop such an extremely advanced perfusion system, academia-private partnership between Erasmus MC and Organ Assist MedTech company is paramount to join stem cell technology with innovative technical perfusion strategies.

A stunning 29 million Europeans suffer from a chronic liver condition, responsible for 150,000 deaths annually. Liver transplantation is the only effective treatment, but the number of good quality donor organs is desperately insufficient to meet the need. In fact, despite an adaptation of the Organ Donation Act just accepted by the Dutch Parliament, suitable donor organs are declining at alarming speed due to increasing age and obesity of the donor population. Thus, one in five patients will not make it to transplantation while on the waiting list.

Recently, our group was able to grow patient-specific liver stem cells (organoids) from both healthy and diseased liver tissue. These stem cells can be expanded infinite and can be used to fill an empty liver biomatrix with healthy cells. Understanding liver organoid recellularization and differentiation capacity in this empty liver biomatrix is the key to revolutionize organ transplantation as an on-demand personalized tissue transplantation without dependence on human organ donors. Better perfusion devices are needed to support multi-stage recellularization.

Key deliverables are human liver biomatrix (scaffolds) of known composition and tested biological safety to serve as transplantable carriers. Also, optimal closed loop perfusion conditions for long-term reseeding procedures will be formulated and finally, recellularization strategies to get the stem cells in the liver biomatrix will be developed.

At the end of the project we aim to grow a liver outside the body and measure developing liver function with non-invasive techniques.