hDAF expression in hearts of transgenic pigs obtained by sperm-mediated gene transfer
| Autor: | Antonella Stoppacciaro, Gabriella Marfe, M.L Bacci, G Della Casa, Marialuisa Lavitrano, Giorgio Stassi, L Renzi, V Turchi, P Sinibaldi, C Di Stefano, Raffaello Cortesini, Francesco Cappello, R. Pretagostini, Hongjun Wang, Luigi Frati, Massimo Rossi, P Giancotti, Paolo Bruzzone, Monica Forni, Davide Lazzereschi |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Swine Transgene Xenotransplantation medicine.medical_treatment Transplantation Heterologous Biology Animals Genetically Modified Sperm-mediated gene transfer DAF transgenic xenotransplantation Antigens CD medicine Animals Humans Decay-accelerating factor Genetics Transplantation CD55 Antigens Myocardium Genetic transfer Gene Transfer Techniques Immunohistochemistry Spermatozoa Complement system Cell biology Genetically modified organism Transgenesis Surgery |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0041-1345 |
| Popis: | TRANSPLANTATON has been the choice option to treat successfully an increasing number of acute and chronic human pathologies with declining morbidity and mortality. However, availability of organs from human donors is limited and dramatically inadequate with respect to patient requests. Xenotransplantation from large-sized mammals has thus been reconsidered as a tool to overcome the present unbalance between organ offers and requests. Pigs have been chosen because they can be easily and cheaply bred; they do not raise ethical questions—their use as alimentary resources is generally admitted; and they possess organs largely human compatible for size, anatomical organization, and physiology. Nevertheless, this option is usually compromised by the occurrence of an irreversible hyperacute vascular rejection of the animal transplanted organ as soon as it is perfused with human blood, mediated by natural preformed antibodies and by the activation of the complement cascade. Downregulating the complement system by expressing on the surface of the swine organs one or more species-specific negative modulators of the complement complexes, such as human decay accelerating factor (hDAF), could prevent the rejection of the graft. Our group has obtained a number of transgenic pigs for hDAF using sperm-mediated gene transfer (SMGT), an innovative and highly efficient and reproducible method. In SMGT, spermatozoa are employed as natural vectors of foreign DNA and are bound, captured, and internalized into recipient egg cells to generate a genetically modified progeny. Revealing the expression of the protein on the surface of the organs is an important confirmation for successful transgenesis. The aim of this report is to show, by immunohistochemical detection, the expression of hDAF in transgenic hearts, organs maximally eligible for xenotransplantation. |
| Databáze: | OpenAIRE |
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