| Title: |
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 |
| Authors: |
Vela, Maria; Stringa, Pablo; González Navarro, Pablo; Machuca, Mariana; Pascual Miguel, Bárbara; Mestre, Carmen; Arreola, Nidia M.; Papa Gobbi, Rodrigo; Navarro Zapata, Alfonso; Pires Lobo, Sara C.; Andrés, Ane M.; Hernández Oliveros, Francisco; Pérez Martínez, Antonio |
| Contributors: |
Departamento de Pediatría; Facultad de Medicina |
| Publisher Information: |
Wiley Blackwell Publishing, Inc |
| Publication Year: |
2024 |
| Collection: |
Universidad Autónoma de Madrid (UAM): Biblos-e Archivo |
| Subject Terms: |
animal model; chimerism; fludarabine; graft-versus-host disease; intestinal passenger T leukocytes; intestine transplantation; Medicina |
| Description: |
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 ; This work was supported in part by Hospital La Paz Institute for Health Research (IdiPAZ) (TRASCHILD project), by NUPA (Patients association for parenteral nutrition and intestinal transplantation) grant to Montserrat Arreola, CRIS CANCER Foundation grant to Barbara Pascual-Miguel and by Mutua Madrileña Foundation grant to Francisco Hernández Oliveros |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Transplant International; https://doi.org/10.1111/tri.13672; https://hdl.handle.net/10486/715641; 1302; 10; 1311; 33 |
| DOI: |
10.1111/tri.13672 |
| Availability: |
https://hdl.handle.net/10486/715641; https://doi.org/10.1111/tri.13672 |
| Rights: |
© 2020 Steunstichting ESOT ; http://creativecommons.org/licenses/by-nc-sa/4.0/ ; Reconocimiento – NoComercial – CompartirIgual ; open access |
| Accession Number: |
edsbas.124BFEB |
| Database: |
BASE |