Wiebe, Karsten and Oezkur, Mehmet and Poeling, Jochen and Haverich, Axel (2006) Potential of an injectable polymer to prevent hyperacute rejection of ex vivo perfused porcine lungs. TRANSPLANTATION, 82 (5). pp. 681-688. ISSN 0041-1337,
Full text not available from this repository. (Request a copy)Abstract
Background. Removal of xenoreactive antibodies in pig-to-human lung transplantation by columns or organ perfusions proofed to be unsatisfactory and associated with adverse effects. In an ex-vivo lung perfusion model, we evaluated the potential of a soluble trisaccharide polymer (GAS914) to bind alpha-Gal antibodies and to protect a pulmonary xenograft from hyperacute rejection (HAR) and pulmonary xenograft dysfunction. Methods. Porcine lungs were perfused with fresh human blood for 240 min. In the GAS914 treated group (n = 6) the polymer was applied in three different concentrations. The control group (n = 6) received no GAS914. Survival and function of perfused xenografts were monitored, and alpha-Gal antibodies as well as cytolytic anti-porcine antibodies analyzed. Results. In the GAS-treated group survival of lungs was significantly prolonged, pulmonary vascular resistance reduced, pulmonary edema prevented, and oxygenation improved. On histopathological evaluation application of GAS resulted in minimal graft injury and significantly less deposition of the terminal complement Complex C5b-9. Following application of GAS914, up to 89.8% of IgG alpha-Gal, 79.5% of IgM and 73.6% of anti-porcine antibodies in the human blood were bound by the polymer. Subsequent perfusion of porcine lungs resulted in absorption of only 3% of the baseline IgG alpha-Gal antibodies in the GAS914 group, compared to 87% in the controls. Conclusions. In this ex-vivo lung perfusion model, a trisaccharide polymer prevented immediate HAR, due to effective removal of a-Gal antibodies. In combination with additional strategies GAS914 may be a valuable tool in overcoming HAR and dysfunction of pulmonary xenografts.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BABOON HEART-TRANSPLANTATION; ANTI-PIG ANTIBODIES; TO-HUMAN MODEL; PULMONARY XENOTRANSPLANTATION; IN-VITRO; XENOGRAFT REJECTION; NATURAL ANTIBODIES; CYNOMOLGUS MONKEYS; ALPHA-GAL; ORGAN XENOTRANSPLANTATION; xenotransplantation; GAS914; alpha-Gal antibody; hyperacute rejection; pulmonary xenograft dysfunction |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Jan 2021 13:19 |
| Last Modified: | 27 Jan 2021 13:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34023 |
Actions (login required)
 |
View Item |
