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(1/2)
Date Issued
2003-07-31
Date
2003-07-31
Author(s)
李章銘
DOI
912314B002233
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 the HLA DR exogene once expressed on the pig cell has a tendency to reduce
the xenogenic cellular response if the human responder PBMC has the same HLA DR
gene as the transgenic pig. The confirmative study is on the way at the present time.
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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