異種器官供人體移植之可行性研究-使用多基因轉殖小鼠與豬器官─HO-1/hDAF/HLA-DR多基因轉殖豬細胞體外之功能測試(2/2)
Date Issued
2004-07-31
Date
2004-07-31
Author(s)
李章銘
DOI
922314B002226
Abstract
Pig to human xenotransplatation is a promising strategy to overcome the organ shortage in
clinical transplantation. However, the application is hampered by the xenoreactive antibody
mediated hyperacute rejection, delayed xenograft rejection and MHC disparity associated T cell
rejection. Previous, we have produced the HLA DPW0401 transgenic pig, which was shown
equipped with the human HLA antigenecity and, as compared to the non-transgenic litermate pig,
induced a minor cellular response to the human PBMCs that came from the HLA DPW 0401(+)
human. HO-1 (heme oxygenase-1) is the main enzyme metabolizing the heme, which has been
demonstrated to offer a protective effect for the xenograft to achieve accommodation under the
presence of xenoreactive antibodies, and help to attenuate xenoantibody mediated celll lysis and
apoptosis. To test the protective effect of HO-1 exogene from the NK related cytotoxicity, we have
establish the optimal condition for this cytotoxic assay using the NK cell line, K562. The cell
killing efficacy will be maximal when the effector/target ratio being 5: 1, 47% of cell death of the
total cell population. We have also successfully cultured the aortic endothelial cells of pig (PAEC)
from the non-transgenic pig. The culture of the PAEC of the transgenic pig is ongoing now.
Because the HLA-DR 1501 has been successfully produced, we also test the xenogenic MLC for the
HLA DR transgenic pig. We found that the tendency about xenogenic cellular response was not
evidently different between the HLADR transgenic and non-transgenic littermate control pis PBMC.
Whether this transgenic pig cell can obtain protective effect in another process of xenogenic immune
response required to be examined further.
Subjects
Transgenic Pig
Xenotransplantation
HLA
HO-1
hDAF
Publisher
臺北市：國立臺灣大學醫學院外科
Type
report
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