Modalities and future prospects of gene therapy in heart transplantation.

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Serval ID
serval:BIB_51690BCD777B
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Modalities and future prospects of gene therapy in heart transplantation.
Journal
European Journal of Cardio-thoracic Surgery
Author(s)
Vassalli G., Roehrich M.E., Vogt P., Pedrazzini G.B., Siclari F., Moccetti T., von Segesser L.K.
ISSN
1873-734X[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
35
Number
6
Pages
1036-44
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review Publication Status: ppublish
Abstract
Heart transplantation is the treatment of choice for many patients with end-stage heart failure. Its success, however, is limited by organ shortage, side effects of immunosuppressive drugs, and chronic rejection. Gene therapy is conceptually appealing for applications in transplantation, as the donor organ is genetically manipulated ex vivo before transplantation. Localised expression of immunomodulatory genes aims to create a state of immune privilege within the graft, which could eliminate the need for systemic immunosuppression. In this review, recent advances in the development of gene therapy in heart transplantation are discussed. Studies in animal models have demonstrated that genetic modification of the donor heart with immunomodulatory genes attenuates ischaemia-reperfusion injury and rejection. Alternatively, bone marrow-derived cells genetically engineered with donor-type major histocompatibility complex (MHC) class I or II promote donor-specific hyporesponsiveness. Genetic engineering of naïve T cells or dendritic cells may induce regulatory T cells and regulatory dendritic cells. Despite encouraging results in animal models, however, clinical gene therapy trials in heart transplantation have not yet been started. The best vector and gene to be delivered remain to be identified. Pre-clinical studies in non-human primates are needed. Nonetheless, the potential of gene therapy as an adjunct therapy in transplantation is essentially intact.
Keywords
Gene Therapy/methods, Gene Therapy/trends, Gene Transfer Techniques, Genetic Vectors, Graft Rejection/immunology, Graft Rejection/prevention & control, Heart Transplantation, Humans, Inflammation Mediators/metabolism, Lymphocyte Activation, T-Lymphocytes/immunology
Pubmed
Web of science
Open Access
Yes
Create date
18/11/2009 12:08
Last modification date
14/02/2022 7:55
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