David Al-Adra
Constanca Figueiredo
Nicco Krezdorn- 1Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
- 2Institute for Transfusion Medicine, Hannover Medical School, Hanover, Germany
- 3Clinic for Plastic, Aesthetic, Hand and Reconstructive Surgery, Center for Surgery, Hannover Medical School, Hanover, Germany
Editorial on the Research Topic
Ex-vivo graft preservation and modification
Organ transplantation is the best treatment for end-stage organ disease. However, the demand for suitable organs for transplant outweighs the supply, which has led to the expansion of the donor pool using marginal quality organs (1). With respect to kidneys, marginal organs may carry higher risks, but they have been shown to be better for patients than dialysis (2, 3). To mitigate the risks associated with marginal organs ex vivo machine perfusion has been implemented for a variety of solid organs (4–6). Variations on ex vivo perfusion technology have extended donor organ cold ischemia time, allowed for organ assessment, and opened the possibility of organ rehabilitation with drug-, cell-, or gene-therapy. As such, these perfusion platforms may allow therapies for the reduction of ischemia-reperfusion injury and attenuation of allo- or xenogeneic immunogenicity. Therefore, this Research Topic aims to showcase state-of-the-art techniques in ex vivo organ preservation and modification.
Vargas et al. begin the Research Topic with a review summarizing the rapidly advancing field of ex vivo perfusion technology with respect to the liver. This review discusses immunomodulation, gene therapy and pharmacotherapy to modify a liver graft prior to transplant using ex vivo perfusion. Although organ preservation via ex vivo perfusion systems is promising, this manuscript concludes by reflecting on the many steps still to overcome prior to the translation of these experimental ex vivo techniques to the clinical setting. One such clinical obstacle is determining the optimal oxygen carrier to supply adequate tissue oxygenation to meet the physiological metabolic demand of ex vivo perfusion when conducted at normothermic temperatures. To this end, Rother et al. studied the effects of three different oxygen carriers on porcine kidneys undergoing normothermic ex vivo perfusion. Using the Kidney Assist® device, the authors show similar kidney tissue integrity between oxygen carriers. However, using real-time polymerase chain reaction and Luminex techniques, the authors also show lower immunogenicity of the kidney after perfusion with all synthetic oxygen carriers vs. red blood cells. Similar to our recent findings in the liver, these results suggest alternative oxygen carriers to red blood cells are effective, may be more available, and have immunological advantages over packed red blood cells (7). Furthermore, Hofmann et al. presented an overview on the potential of using human amniotic membrane (hAM)-derivatives in decreasing immunogenicity and supporting tissue regeneration.
In addition to prolonging organ storage and offering functional assessment, one of the most exciting aspects of ex vivo perfusion is the unique advantage of being able to deliver therapeutics directly to the organ. However, not all ex vivo modifications require perfusion. In the study by Gao et al. recombinant adeno-associated virus (rAAV) is used to transduce rat livers with the firefly luciferase gene while undergoing cold storage. After syngeneic liver transplantation, control animals demonstrated no bioluminescent activity, while animals receiving rAAV-treated livers demonstrated gene expression based on bioluminescence and quantitative polymerase chain reaction. Taken together, these results show the effectiveness of rAAV mediated gene transduction in liver grafts when administered during cold storage.
Contained withing this Research Topic, we have demonstrated the latest techniques of ex vivo graft preservation and modification. Future studies will continue to expand the use of ex vivo perfusion and modification to expand the use of marginal organs for transplantation.
Author contributions
DA: Writing – original draft, Writing – review & editing. CF: Writing – original draft, Writing – review & editing. NK: Writing – original draft, Writing – review & editing.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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References
1. Schladt DP, Israni AK. OPTN/SRTR 2021 annual data report: introduction. Am J Transplant. (2023) 23(2 Suppl 1):S12–20. doi: 10.1016/j.ajt.2023.02.003
2. Sharma N, Mahajan A, Qazi YA. Marginal kidney transplantation: the road less traveled. Curr Opin Organ Transplant. (2019) 24(1):92–6. doi: 10.1097/MOT.0000000000000603
3. Jay CL, Washburn K, Dean PG, Helmick RA, Pugh JA, Stegall MD. Survival benefit in older patients associated with earlier transplant with high KDPI kidneys. Transplantation. (2017) 101(4):867–72. doi: 10.1097/TP.0000000000001405
4. Nasralla D, Coussios CC, Mergental H, Akhtar MZ, Butler AJ, Ceresa CDL, et al. A randomized trial of normothermic preservation in liver transplantation. Nature. (2018) 557(7703):50–6. doi: 10.1038/s41586-018-0047-9
5. Hosgood SA, Callaghan CJ, Wilson CH, Smith L, Mullings J, Mehew J, et al. Normothermic machine perfusion versus static cold storage in donation after circulatory death kidney transplantation: a randomized controlled trial. Nat Med. (2023) 29(6):1511–9. doi: 10.1038/s41591-023-02376-7
6. Divithotawela C, Cypel M, Martinu T, Singer LG, Binnie M, Chow CW, et al. Long-term outcomes of lung transplant with ex vivo lung perfusion. JAMA Surg. (2019) 154(12):1143–50. doi: 10.1001/jamasurg.2019.4079
Keywords: ex-vivo, transplantation, organ preservation and perfusion, organ modification, organ donation
Citation: Al-Adra D, Figueiredo C and Krezdorn N (2023) Editorial: Ex vivo graft preservation and modification. Front. Transplant. 2:1291543. doi: 10.3389/frtra.2023.1291543
Received: 9 September 2023; Accepted: 12 October 2023;
Published: 23 October 2023.
Edited and Reviewed by: Jerzy Kupiec-Weglinski, University of California, United States
© 2023 Al-Adra, Figueiredo and Krezdorn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: David Al-Adra aladra@wisc.edu
†These authors share senior authorship
Abbreviations rAAV, recombinant adeno-associated virus; hAM, human amniotic membrane.