A perspective on the potential detrimental role of inflammation in pig orthotopic heart xenotransplantation.

Tytuł:: A perspective on the potential detrimental role of inflammation in pig orthotopic heart xenotransplantation.
Autorzy:: Thompson CP; Xenotransplantation Program, Division of Transplantation, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Jagdale A; Xenotransplantation Program, Division of Transplantation, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Walcott G; Department of Medicine/Cardiovascular Diseases, the University of Alabama at Birmingham, Birmingham, AL, USA.
Iwase H; Xenotransplantation Program, Division of Transplantation, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Foote JB; Department of Microbiology and Animal Resources Program, University of Alabama at Birmingham, Birmingham, AL, USA.
Cron RQ; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Hara H; Xenotransplantation Program, Division of Transplantation, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Cleveland DC; Division of Cardiothoracic Surgery, Children's Hospital of Alabama, and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Cooper DKC; Xenotransplantation Program, Division of Transplantation, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Źródło:: Xenotransplantation [Xenotransplantation] 2021 Jul; Vol. 28 (4), pp. e12687. Date of Electronic Publication: 2021 Mar 30.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: Copenhagen : Munksgaard International Publishers
Original Publication: Copenhagen : Munksgaard, c1994-
MeSH Terms:: Graft Rejection*/prevention & control
Graft Survival*
Animals ; Animals, Genetically Modified ; Heterografts ; Humans ; Inflammation ; Swine ; Transplantation, Heterologous
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Grant Information:: U19 AI090959 United States AI NIAID NIH HHS
Contributed Indexing:: Keywords: cardiopulmonary bypass; cytokines; inflammation; interleukin-6; xenotransplantation
Entry Date(s):: Date Created: 20210331 Date Completed: 20210917 Latest Revision: 20220424
Update Code:: 20240104
DOI:: 10.1111/xen.12687
PMID:: 33786912
: Czasopismo naukowe

Pełny tekst

There is a critical shortage of deceased human donor organs for transplantation. The need is perhaps most acute in neonates and infants with life-threatening congenital heart disease, in whom mechanical support devices are largely unsuccessful. If orthotopic (life-supporting) heart transplantation (OHTx) were consistently successful in the genetically engineered pig-to-nonhuman primate (NHP) model, a clinical trial of bridging with a pig heart in such patients might be justified. However, the results of pig OHTx in NHPs have been mixed and largely poor. We hypothesise that a factor is the detrimental effects of the inflammatory response that is known to develop (a) during any surgical procedure that requires cardiopulmonary bypass, and (b) immediately after an NHP recipient is exposed to a pig xenograft. We suggest that the combination of these two inflammatory responses has a direct detrimental effect on pig heart graft function, but also, and possibly of more importance, on recipient baboon pulmonary function, which further impacts survival of the pig heart graft. In addition, the inflammatory response almost certainly adversely impacts the immune response to the graft. If our hypothesis is correct, the potential steps that could be taken to reduce the inflammatory response or its effects (with varying degrees of efficacy) include (a) white blood cell filtration, (b) complement depletion or inactivation, (c) immunosuppressive therapy, (d) high-dose corticosteroid therapy, (e) cytokine/chemokine-targeted therapy, (f) ultrafiltration or CytoSorb hemoperfusion, (g) reduction in the levels of endogenous catecholamines, (h) triiodothyronine therapy and (i) genetic engineering of the organ-source pig. Prevention of the inflammatory response, or attenuation of its effects, by judicious anti-inflammatory therapy may contribute not only to early survival of the recipient of a genetically engineered pig OHTx, but also to improved long-term pig heart graft survival. This would open the possibility of initiating a clinical trial of genetically engineered pig OHTx as a bridge to allotransplantation.
(© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Comment in: Xenotransplantation. 2022 Jan;29(1):e12734. (PMID: 35165939)

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