Donor's graft ex vivo T-cell depletion with fludarabine reduces graft-versus-host disease signs and improves survival after intestinal transplantation - an experimental study.
animal model
chimerism
fludarabine
graft-versus-host disease
intestinal passenger T leukocytes
intestine transplantation
Journal
Transplant international : official journal of the European Society for Organ Transplantation
ISSN: 1432-2277
Titre abrégé: Transpl Int
Pays: Switzerland
ID NLM: 8908516
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
04
03
2020
revised:
31
03
2020
accepted:
05
06
2020
pubmed:
12
6
2020
medline:
25
6
2021
entrez:
12
6
2020
Statut:
ppublish
Résumé
Intestinal passenger T leukocytes are responsible for graft-versus-host disease (GvHD) in intestinal transplantation (ITx). We hypothesized that ex vivo fludarabine treatment of the bowel graft would diminish the risk of GvHD and improve overall survival post-transplant. We performed isolated heterotopic small bowel transplantations from Lewis (LEW) to Brown Norway (BN) rat strains, which generated GvHD signs from the fourth day post-transplant. These symptoms included rash, weight loss, piloerection, and diarrhea. The grafts of one of the experimental groups were immersed and sealed in cold Celsior preservation solution with 1000 µm fludarabine for 1 h, prior to its implantation into recipient animals. No histological signs of intestinal tissue alterations were observed after fludarabine treatment. Fludarabine-treated bowel recipients showed significantly later and milder clinical signs of GvHD and reduced total donor cell chimerism, as determined by flow cytometry using strain-specific anti-HLA antibodies. Additionally, fludarabine treatment prolonged recipients' overall survival (13.5 days ± 0.3 days vs. 9.2 days ± 0.5). We conclude that active modification of the intestinal leukocyte composition is advantageous in our ITx animal model. Immunosuppression with fludarabine during the surgical procedure, which could be translated directly to the clinic, protects bowel recipients from GvHD and improves overall post-transplant survival.
Substances chimiques
Vidarabine
FA2DM6879K
fludarabine
P2K93U8740
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1302-1311Subventions
Organisme : NUPA (Patients association for parenteral nutrition and intestinal transplantation)
Organisme : Hospital La Paz Institute for Health Research (IdiPAZ)
Organisme : Mutua Madrileña Foundation
Informations de copyright
© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.
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