Selective Repopulation of Mice Liver after Fas-Resistant Hepatocyte Transplantation
Hepatocyte transplantation has been proposed as a potential therapeutic method to treat irreversible liver failure and inherited hepatic disorders, although transplanted cells do not easily reconstruct the liver tissue under intact conditions. This study was aimed at modulating the recipient liver c...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2001-05-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/000000001783986701 |
| _version_ | 1818539592830156800 |
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| author | Masayuki Fujino Xiao-Kang Li M.D., Ph.D. Yusuke Kitazawa Naoko Funeshima Lei Guo Torayuki Okuyama Takashi Amano Hiroshi Amemiya Seiichi Suzuki |
| author_facet | Masayuki Fujino Xiao-Kang Li M.D., Ph.D. Yusuke Kitazawa Naoko Funeshima Lei Guo Torayuki Okuyama Takashi Amano Hiroshi Amemiya Seiichi Suzuki |
| author_sort | Masayuki Fujino |
| collection | DOAJ |
| description | Hepatocyte transplantation has been proposed as a potential therapeutic method to treat irreversible liver failure and inherited hepatic disorders, although transplanted cells do not easily reconstruct the liver tissue under intact conditions. This study was aimed at modulating the recipient liver conditions to promote repopulation of the liver after hepatocyte transplantation. Hepatocytes isolated from male MRL-lpr/lpr (lpr) mice with a mutation of Fas antigen were transplanted in a number of 1 × 106 cells in female MRL-+/+ (wildtype mice) by intrasplenic injection. An agonistic anti-Fas antibody (0.15 mg/kg) was administered intravenously 24 h after cell transplantation. We also administrated the antibody at 0.3 mg/kg 1 week after grafting and at 0.6 mg/kg 2 weeks after transplantation. The liver specimens were taken at different time intervals for histological examination. The reconstructed male lpr hepatocytes in the female wild-type mice were determined by a real-time quantitative PCR assay using the primers and probe for the sry gene. The pathologic findings of the recipient livers after treatment with anti-Fas antibody revealed a large number of apoptotic hepatocytes. The grafted lpr hepatocytes were observed to reconstruct as much as 6.9% of the recipient liver in the anti-Fas antibody-treated group 3 months after transplantation. In contrast, we observed the transplanted cells at lower than 0.1% in the nontreated livers. These findings demonstrated that repeated induction of apoptosis in recipient hepatocytes shifts the environment of the liver to a regenerative condition. This method may be useful to promote the reconstruction of transplanted hepatocytes in a recipient liver. |
| first_indexed | 2024-12-11T21:44:07Z |
| format | Article |
| id | doaj.art-b4aeb4a121c9413a87d8970688b86444 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-11T21:44:07Z |
| publishDate | 2001-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-b4aeb4a121c9413a87d8970688b864442022-12-22T00:49:42ZengSAGE PublishingCell Transplantation0963-68971555-38922001-05-011010.3727/000000001783986701Selective Repopulation of Mice Liver after Fas-Resistant Hepatocyte TransplantationMasayuki Fujino0Xiao-Kang Li M.D., Ph.D.1Yusuke Kitazawa2Naoko Funeshima3Lei Guo4Torayuki Okuyama5Takashi Amano6Hiroshi Amemiya7Seiichi Suzuki8Department of Zootechnical Science, Tokyo University of Agriculture, Tokyo, JapanDepartment of Experimental Surgery and Bioengineering, Tokyo, JapanDepartment of Experimental Surgery and Bioengineering, Tokyo, JapanDepartment of Experimental Surgery and Bioengineering, Tokyo, JapanDepartment of Experimental Surgery and Bioengineering, Tokyo, JapanGenetics, National Children's Medical Research Center, Tokyo, JapanDepartment of Zootechnical Science, Tokyo University of Agriculture, Tokyo, JapanDepartment of Experimental Surgery and Bioengineering, Tokyo, JapanDepartment of Experimental Surgery and Bioengineering, Tokyo, JapanHepatocyte transplantation has been proposed as a potential therapeutic method to treat irreversible liver failure and inherited hepatic disorders, although transplanted cells do not easily reconstruct the liver tissue under intact conditions. This study was aimed at modulating the recipient liver conditions to promote repopulation of the liver after hepatocyte transplantation. Hepatocytes isolated from male MRL-lpr/lpr (lpr) mice with a mutation of Fas antigen were transplanted in a number of 1 × 106 cells in female MRL-+/+ (wildtype mice) by intrasplenic injection. An agonistic anti-Fas antibody (0.15 mg/kg) was administered intravenously 24 h after cell transplantation. We also administrated the antibody at 0.3 mg/kg 1 week after grafting and at 0.6 mg/kg 2 weeks after transplantation. The liver specimens were taken at different time intervals for histological examination. The reconstructed male lpr hepatocytes in the female wild-type mice were determined by a real-time quantitative PCR assay using the primers and probe for the sry gene. The pathologic findings of the recipient livers after treatment with anti-Fas antibody revealed a large number of apoptotic hepatocytes. The grafted lpr hepatocytes were observed to reconstruct as much as 6.9% of the recipient liver in the anti-Fas antibody-treated group 3 months after transplantation. In contrast, we observed the transplanted cells at lower than 0.1% in the nontreated livers. These findings demonstrated that repeated induction of apoptosis in recipient hepatocytes shifts the environment of the liver to a regenerative condition. This method may be useful to promote the reconstruction of transplanted hepatocytes in a recipient liver.https://doi.org/10.3727/000000001783986701 |
| spellingShingle | Masayuki Fujino Xiao-Kang Li M.D., Ph.D. Yusuke Kitazawa Naoko Funeshima Lei Guo Torayuki Okuyama Takashi Amano Hiroshi Amemiya Seiichi Suzuki Selective Repopulation of Mice Liver after Fas-Resistant Hepatocyte Transplantation Cell Transplantation |
| title | Selective Repopulation of Mice Liver after Fas-Resistant Hepatocyte Transplantation |
| title_full | Selective Repopulation of Mice Liver after Fas-Resistant Hepatocyte Transplantation |
| title_fullStr | Selective Repopulation of Mice Liver after Fas-Resistant Hepatocyte Transplantation |
| title_full_unstemmed | Selective Repopulation of Mice Liver after Fas-Resistant Hepatocyte Transplantation |
| title_short | Selective Repopulation of Mice Liver after Fas-Resistant Hepatocyte Transplantation |
| title_sort | selective repopulation of mice liver after fas resistant hepatocyte transplantation |
| url | https://doi.org/10.3727/000000001783986701 |
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