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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-11-24
pubmed:abstractText
The effects of OX40-OX40 ligand (OX40L) costimulatory pathway blockade to prevent T-cell-mediated acute rejection were investigated in a rat model of allogeneic superficial inferior epigastric artery flap transplantation. An ex vivo gene transfer technique was used to modify allografts to locally deliver an immunomodulatory molecule. The flaps were separated from donors, perfused with an adenoviral vector expressing the OX40 immunoglobulin (AdOX40Ig) for 1 hour, and incubated at 37°C for 2 hours. Before transplantation, the flaps were flushed with phosphate-buffered saline solution to remove unincorporated viral particles. Recipients were randomly divided into 5 groups, and treated with topical OX40Ig gene transfer, a single low dose of rapamycin alone, or a combination of agents. Graft survival was assessed using histopathologic classification of skin rejection. All animals in the untreated group (n = 9) or the group treated with adenovirus expressing green fluorescence protein (n = 9) developed grade 3 clinical rejection by postoperative day 7. No significant difference was observed in graft survival between the locally treated AdOX40Ig groups (mean [SD], 8.1 [0.7] days) and the untreated groups (7.7 [1.2] days) could be observed (P > .05, t test). Graft survival in the locally treated AdOX40Ig groups was extended to 18.7 (1.2) days when transduction was combined with a low dose of rapamycin, a significant improvement over survival with rapamycin treatment alone (13.2 [0.6] days) (P < .01). These results demonstrated that local immunomodulation by the allograft itself and low-dose rapamycin treatment promote graft acceptance. This protocol may enable reduction of the dosage of immunosuppressive drugs needed for successful inhibition of acute rejection in the early postoperative period.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1873-2623
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3815-9
pubmed:meshHeading
pubmed-meshheading:21094862-Acute Disease, pubmed-meshheading:21094862-Adenoviridae, pubmed-meshheading:21094862-Animals, pubmed-meshheading:21094862-Antigens, Differentiation, pubmed-meshheading:21094862-Combined Modality Therapy, pubmed-meshheading:21094862-Gene Therapy, pubmed-meshheading:21094862-Genetic Vectors, pubmed-meshheading:21094862-Graft Rejection, pubmed-meshheading:21094862-Graft Survival, pubmed-meshheading:21094862-Immunosuppression, pubmed-meshheading:21094862-Immunosuppressive Agents, pubmed-meshheading:21094862-Membrane Glycoproteins, pubmed-meshheading:21094862-Models, Animal, pubmed-meshheading:21094862-Rats, pubmed-meshheading:21094862-Rats, Inbred BN, pubmed-meshheading:21094862-Rats, Inbred Lew, pubmed-meshheading:21094862-Sirolimus, pubmed-meshheading:21094862-Skin Transplantation, pubmed-meshheading:21094862-Surgical Flaps, pubmed-meshheading:21094862-Time Factors, pubmed-meshheading:21094862-Transplantation, Homologous, pubmed-meshheading:21094862-Tumor Necrosis Factors
pubmed:year
2010
pubmed:articleTitle
Use of genetically modified allograft to deliver local immunomodulatory molecule with minimal systemic toxicity in a rat model of allogeneic skin flap transplantation.
pubmed:affiliation
Institute of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shanxi Province, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't