01 January 2014 → 14 April 2015
Regional and community funding: Industrial Research Fund
Research disciplines
  • Medical and health sciences
    • Immunology
    • Immunology
    • Immunology
connexins cell death vitrification (cryo)preservation viability
Project description

Grafts consisting of entire organs like heart or kidney, composite tissues like blood vessels and embryos, or a collection of dispersed cells like stem cells and hepatocytes are often preserved via cold storage, cryopreservation or vitrification before they are transplanted in /or transferred to animals including humans. While cooling in general is necessary to preserve some degree of cell viability within the graft, by slowing down potentially toxic chemical processes, the procedure is intrinsically associated with various degrees of cell stress that may ultimately result in cell damage and cell death. Gap junctions and connexin hemichannels (half gap junction channels) play a role in cell death processes. Gap junctions allow the passage of cell death messengers thereby contributing to the propagation of cell death known as bystander cell death. Unapposed hemichannels may promote cell death by uncontrolled opening and thereby contribute, as a toxic pore, to the entrance or escape from the cell of ions and small metabolites. Inhibiting connexin channels may thus lead to improved cell viability after exposure to cooling/freezing related stress associated with these preservation techniques. A recent patent application from our research group focused on a method to protect grafts against cell death based on blocking gap junctions and hemichannels by making use of connexin/pannexin mimetic peptides in the preservation/thawing medium. In particular, we were able to demonstrate that connexin mimetic peptides reduce cell death in cryopreserved/thawed human blood vessels. Supplemental data and evidence from other tissues and cell systems are however needed in order to expand and strenghten the proof of concept and to prepare a licencing track.