The clinical realization of machine-based organ and tissue preservation opens up a novel chapter in medicine. This technology allows ex vivo organ/tissue perfusion, hence mimicking an in vivo situation while bridging the time to transplantation. It further minimizes the duration of true ischemia and offers assessment of organ viability, quality, and function during this state. Most importantly, this innovative preservation technology provides the unique possibility of organ/tissue reconditioning, immunomodulation, regeneration, and treatment while outside the human body.
So far, the impact of ex vivo machine perfusion on the immunological status of an organ/tissue is largely unknown. Advances in multi-color flow cytometry, next-generation sequencing technologies, and platforms at single-cell population levels have recently opened up new opportunities to draw an accurate picture of cell compositions, and compositions and provide novel insights into immune responses and their dynamic changes over time within machine-perfused organs/tissues.
During transplantation, a significant amount of donor leukocytes residing in the graft is transplanted to the recipient and favors direct recognition of MHC class II alloantigens on donor antigen-presenting cells by recipient T cells. There is evidence that during machine perfusion a great number of passenger leukocytes extravasate into the perfusate. The concept of mobilization and removal of a proportion of passenger leukocytes and cytokines prior to transplantation may hold great potential to reduce ischemia/reperfusion injury and acute allograft rejection and ultimately improve clinical outcomes. Moreover, ex vivo machine perfusion provides a unique platform in order to create an immunologically “masked” organ/tissue, hence reducing the risk of rejection and eventually immunosuppression levels. Replacement of donor cells with patient-specific, non-immunogenic cells could allow for the generation of intra organ/tissue chimerism, which might further reduce alloimmunity. All of these exciting new opportunities for ex vivo organ manipulations could pave the way for the realization of “personalized organs" for transplant in the future.
This Research Topic aims to collect Original Research and state-of-the-art Review and Mini-Review articles on assessment of the immunologic status, the dynamic change, and the possibility of immunomodulation/-masking of organs and tissues during ex vivo machine perfusion, including, but not limited to, the following sub-topics:
1. Characterizing cell migration and leukocyte trafficking during machine perfusion of organs and tissues
2. Characterizing the immune response during machine perfusion of organs and tissues
3. Utilization of immune repertoire profiling in the perfusate during machine perfusion to assess organ quality and transplantation outcome
4. Advances and limitations of novel sequencing platforms to evaluate immunological processes and understand the impact of machine perfusion on immunomodulation of healthy and diseased organs and tissues
5. The role of ischemia/reperfusion injury and immune activation in the course of machine perfusion of organs and tissues
6. Pre-conditioning regimens during machine perfusion of organs and tissues to attenuate ischemia/reperfusion injury and immune activation
7. Potential options of immunomodulation during machine perfusion of organs and tissues to reduce acute rejection after transplantation
8. Generating immunologically masked and “patients-specific” organs and tissues to reduce the alloimmune response and eventually immunosuppression after transplantation.
Topic Editor Stefan Schneeberger received financial support from Neovii and Organ Recovery. The other Topic Editors declare no competing interests.
The clinical realization of machine-based organ and tissue preservation opens up a novel chapter in medicine. This technology allows ex vivo organ/tissue perfusion, hence mimicking an in vivo situation while bridging the time to transplantation. It further minimizes the duration of true ischemia and offers assessment of organ viability, quality, and function during this state. Most importantly, this innovative preservation technology provides the unique possibility of organ/tissue reconditioning, immunomodulation, regeneration, and treatment while outside the human body.
So far, the impact of ex vivo machine perfusion on the immunological status of an organ/tissue is largely unknown. Advances in multi-color flow cytometry, next-generation sequencing technologies, and platforms at single-cell population levels have recently opened up new opportunities to draw an accurate picture of cell compositions, and compositions and provide novel insights into immune responses and their dynamic changes over time within machine-perfused organs/tissues.
During transplantation, a significant amount of donor leukocytes residing in the graft is transplanted to the recipient and favors direct recognition of MHC class II alloantigens on donor antigen-presenting cells by recipient T cells. There is evidence that during machine perfusion a great number of passenger leukocytes extravasate into the perfusate. The concept of mobilization and removal of a proportion of passenger leukocytes and cytokines prior to transplantation may hold great potential to reduce ischemia/reperfusion injury and acute allograft rejection and ultimately improve clinical outcomes. Moreover, ex vivo machine perfusion provides a unique platform in order to create an immunologically “masked” organ/tissue, hence reducing the risk of rejection and eventually immunosuppression levels. Replacement of donor cells with patient-specific, non-immunogenic cells could allow for the generation of intra organ/tissue chimerism, which might further reduce alloimmunity. All of these exciting new opportunities for ex vivo organ manipulations could pave the way for the realization of “personalized organs" for transplant in the future.
This Research Topic aims to collect Original Research and state-of-the-art Review and Mini-Review articles on assessment of the immunologic status, the dynamic change, and the possibility of immunomodulation/-masking of organs and tissues during ex vivo machine perfusion, including, but not limited to, the following sub-topics:
1. Characterizing cell migration and leukocyte trafficking during machine perfusion of organs and tissues
2. Characterizing the immune response during machine perfusion of organs and tissues
3. Utilization of immune repertoire profiling in the perfusate during machine perfusion to assess organ quality and transplantation outcome
4. Advances and limitations of novel sequencing platforms to evaluate immunological processes and understand the impact of machine perfusion on immunomodulation of healthy and diseased organs and tissues
5. The role of ischemia/reperfusion injury and immune activation in the course of machine perfusion of organs and tissues
6. Pre-conditioning regimens during machine perfusion of organs and tissues to attenuate ischemia/reperfusion injury and immune activation
7. Potential options of immunomodulation during machine perfusion of organs and tissues to reduce acute rejection after transplantation
8. Generating immunologically masked and “patients-specific” organs and tissues to reduce the alloimmune response and eventually immunosuppression after transplantation.
Topic Editor Stefan Schneeberger received financial support from Neovii and Organ Recovery. The other Topic Editors declare no competing interests.
