Freezing Hearts

Background

Heart failure has become a modern epidemic, with an overall prevalence of 2% in the western world. Despite advances in medical and device therapy, the five-year mortality is still 50%. For patients with advanced heart failure a heart transplantation is the only curative option. However, due to the extreme shortage of usable donor hearts many patients die on the waiting list. Although the shortage of donor organs is partially caused by an insufficient number of registered donors, an equally important cause is the limited quality and matching of potential donor organs. The main reason for this is the current maximum preservation time of 4 hours (from excision to implantation).

Project description

In order to extend the preservation time of hearts, they need to be frozen with extreme control and without ice crystal formation. By taking inspiration from naturally occurring ice-binding proteins, especially antifreeze glycoproteins (AFGPs), new cryoprotectants can be developed to extend heart life-time.

In this project, antifreeze glycoprotein from arctic fish will be produced in Nicotiana bentamiana plants. By engineering the post-translational machinery of the plant, new sugar motifs are introduced that are crucial for the functioning of these AFGPs. These novel bio-inspired cryoprotectants can be applied to preserve whole organs as well as cultured cardiomyocytes, and are elevant to advance the field of regenerative medicine.