Building a new liver from matrix and human stem cells
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 XVIVO (formerly 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-derived cholangiocyte 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-derived 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.
We were able to generate empty liver biomatrices with retained intrinsic properties, which are free of bacteria, fungi, viruses, and endotoxins to meet safety criteria. Also, a closed-loop perfusion system for long-term reseeding procedures was developed, allowing sterile perfusion for 14 days. Different recellularization strategies have been tested, and seeding of new blood vessels was successful. A protocol was established to grow multiple cells from one culture medium and recellularization experiments were successful at small scale. We successfully developed two methods to measure liver function non-invasively during machine perfusion. A major limitation that hampered generation of large segments of functional liver-like tissue, is the lack of large amounts of suitable liver cells. This area is our focus of interest for new projects, to complete our recellularization system into a functional unit.
