Treatment of Acute Liver Failure in Mice by Hepatocyte Xenotransplantation
Liver diseases still have a high mortality even though liver transplantation has become a standard treatment. Currently, hepatocyte transplantation has been proposed as another promising strategy. One limitation is the availability of human livers as a source of hepatocytes. Because of an unlimited...
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doaj-952eb11be60848a2ba14efca2217eceb2020-11-25T03:13:56ZengSAGE PublishingCell Transplantation0963-68971555-38922010-06-011910.3727/096368910X508915Treatment of Acute Liver Failure in Mice by Hepatocyte XenotransplantationTsuyoshi Yamamoto0Nalú Navarro-Alvarez1Alejandro Soto-Gutierrez2Takeshi Yuasa3Masaya Iwamuro4Yasuhiro Kubota5Masayuki Seita6Hironobu Kawamoto7Shahid M. Javed8Eisaku Kondo9Hirofumi Noguchi10Satoru Kobayashi M.D., Ph.D.11Shuhei Nakaji12Naoya Kobayashi13Department of Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, JapanDepartment of Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, JapanDepartment of Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, JapanDepartment of Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, JapanDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, JapanDepartment of Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, JapanDepartment of Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, JapanDepartment of Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, JapanDepartment of Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, JapanDepartment of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, JapanBaylor Research Institute, Islet Cell Transplantation Laboratory, Baylor Institution for Immunology Research, Dallas, TX, USA3-DMatrix, Ltd., Tokyo, JapanDepartment of Biomedical Engineering, School of Engineering, Okayama University of Science, Okayama, JapanDepartment of Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, JapanLiver diseases still have a high mortality even though liver transplantation has become a standard treatment. Currently, hepatocyte transplantation has been proposed as another promising strategy. One limitation is the availability of human livers as a source of hepatocytes. Because of an unlimited supply, the use of porcine hepatocytes might address this problem. Regardless of the source, once isolated hepatocytes lose specific functionality due to the loss of the natural microenvironment. For this reason, we tested the ability of a self-assembling peptide nanofiber (SAPNF) to provide a provisional three-dimensional (3D) support to interact with cells to control their function in vivo. Isolated porcine hepatocytes were embedded in SAPNF, or collagen type I and transplanted by direct injection into the splenic pulp of SCID mice suffering from acute liver failure (ALF) by 90% hepatectomy. SAPNF porcine hepatocyte transplantation produced engraftment that was far superior to that obtained using collagen and prolonged the survival of mice with ALF, in contrast with controls. An ultrastructural evaluation using transmission electron microscopy indicated extensive cell–cell communication and preservation of hepatocyte architecture. The transplanted SAPNF hepatocytes showed higher expression of albumin and PAS and lower apoptotic events assessed by TUNEL staining. Hepatocytes culture in a truly 3D network allows in vivo maintaining of differentiated functions, and once transplanted between widely divergent species can function to correct acute liver failure in mice and prolong their survival.https://doi.org/10.3727/096368910X508915 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tsuyoshi Yamamoto Nalú Navarro-Alvarez Alejandro Soto-Gutierrez Takeshi Yuasa Masaya Iwamuro Yasuhiro Kubota Masayuki Seita Hironobu Kawamoto Shahid M. Javed Eisaku Kondo Hirofumi Noguchi Satoru Kobayashi M.D., Ph.D. Shuhei Nakaji Naoya Kobayashi |
spellingShingle |
Tsuyoshi Yamamoto Nalú Navarro-Alvarez Alejandro Soto-Gutierrez Takeshi Yuasa Masaya Iwamuro Yasuhiro Kubota Masayuki Seita Hironobu Kawamoto Shahid M. Javed Eisaku Kondo Hirofumi Noguchi Satoru Kobayashi M.D., Ph.D. Shuhei Nakaji Naoya Kobayashi Treatment of Acute Liver Failure in Mice by Hepatocyte Xenotransplantation Cell Transplantation |
author_facet |
Tsuyoshi Yamamoto Nalú Navarro-Alvarez Alejandro Soto-Gutierrez Takeshi Yuasa Masaya Iwamuro Yasuhiro Kubota Masayuki Seita Hironobu Kawamoto Shahid M. Javed Eisaku Kondo Hirofumi Noguchi Satoru Kobayashi M.D., Ph.D. Shuhei Nakaji Naoya Kobayashi |
author_sort |
Tsuyoshi Yamamoto |
title |
Treatment of Acute Liver Failure in Mice by Hepatocyte Xenotransplantation |
title_short |
Treatment of Acute Liver Failure in Mice by Hepatocyte Xenotransplantation |
title_full |
Treatment of Acute Liver Failure in Mice by Hepatocyte Xenotransplantation |
title_fullStr |
Treatment of Acute Liver Failure in Mice by Hepatocyte Xenotransplantation |
title_full_unstemmed |
Treatment of Acute Liver Failure in Mice by Hepatocyte Xenotransplantation |
title_sort |
treatment of acute liver failure in mice by hepatocyte xenotransplantation |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2010-06-01 |
description |
Liver diseases still have a high mortality even though liver transplantation has become a standard treatment. Currently, hepatocyte transplantation has been proposed as another promising strategy. One limitation is the availability of human livers as a source of hepatocytes. Because of an unlimited supply, the use of porcine hepatocytes might address this problem. Regardless of the source, once isolated hepatocytes lose specific functionality due to the loss of the natural microenvironment. For this reason, we tested the ability of a self-assembling peptide nanofiber (SAPNF) to provide a provisional three-dimensional (3D) support to interact with cells to control their function in vivo. Isolated porcine hepatocytes were embedded in SAPNF, or collagen type I and transplanted by direct injection into the splenic pulp of SCID mice suffering from acute liver failure (ALF) by 90% hepatectomy. SAPNF porcine hepatocyte transplantation produced engraftment that was far superior to that obtained using collagen and prolonged the survival of mice with ALF, in contrast with controls. An ultrastructural evaluation using transmission electron microscopy indicated extensive cell–cell communication and preservation of hepatocyte architecture. The transplanted SAPNF hepatocytes showed higher expression of albumin and PAS and lower apoptotic events assessed by TUNEL staining. Hepatocytes culture in a truly 3D network allows in vivo maintaining of differentiated functions, and once transplanted between widely divergent species can function to correct acute liver failure in mice and prolong their survival. |
url |
https://doi.org/10.3727/096368910X508915 |
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