Cellular Origins of Regenerating Nodules and Malignancy in the FAH Model of Liver Injury after Bone Marrow Cell Transplantation

In previous reports, we and other groups have shown that proliferating hepatocytes are formed by the fusion of donor hematopoietic cells with host hepatocytes in the Fah−/− model. Thus, it would be interesting to determine whether cell fusion occurs during malignancy. However, it is difficult to dem...

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Main Authors: Pei-Rong Wang, Yi Li
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/5791317
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author Pei-Rong Wang
Yi Li
author_facet Pei-Rong Wang
Yi Li
author_sort Pei-Rong Wang
collection DOAJ
description In previous reports, we and other groups have shown that proliferating hepatocytes are formed by the fusion of donor hematopoietic cells with host hepatocytes in the Fah−/− model. Thus, it would be interesting to determine whether cell fusion occurs during malignancy. However, it is difficult to demonstrate such processes using this model. Therefore, we established a new strain to study the processes of regenerating nodules and malignancy and their origins. The FAH−/− mouse model was crossed with the ROSAnZ strain and their offspring was genotyped for FAH−/− and ROSAnZ mutations to create a new strain (Fah−/−-ROSAnZ). Using this strain as recipients, we performed bone marrow transplantation experiments. As a result, we could not demonstrate the presence of any epithelial cells except hepatocytes that were of donor origin in regenerating tissue, and no evidence of cell fusion was found in tumors. The hepatic malignancy was of host origin in these mice. There was higher expression of extracellular matrix proteins and more inflammatory cells in liver tumor nodules than in regenerating normal liver nodules. Hepatocytes generated by fusion with bone marrow cells did not form malignant tumors. Extracellular matrix and inflammatory cells had significantly accumulated in liver tumors.
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spelling doaj-art-43b1dcd425194fd9aaa7a9494c1c12952025-02-03T01:28:45ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/57913175791317Cellular Origins of Regenerating Nodules and Malignancy in the FAH Model of Liver Injury after Bone Marrow Cell TransplantationPei-Rong Wang0Yi Li1Department of Pediatrics, Second Hospital of Shandong University, Jinan 250033, ChinaDepartment of Medicine, University of Washington, Seattle, WA 98195, USAIn previous reports, we and other groups have shown that proliferating hepatocytes are formed by the fusion of donor hematopoietic cells with host hepatocytes in the Fah−/− model. Thus, it would be interesting to determine whether cell fusion occurs during malignancy. However, it is difficult to demonstrate such processes using this model. Therefore, we established a new strain to study the processes of regenerating nodules and malignancy and their origins. The FAH−/− mouse model was crossed with the ROSAnZ strain and their offspring was genotyped for FAH−/− and ROSAnZ mutations to create a new strain (Fah−/−-ROSAnZ). Using this strain as recipients, we performed bone marrow transplantation experiments. As a result, we could not demonstrate the presence of any epithelial cells except hepatocytes that were of donor origin in regenerating tissue, and no evidence of cell fusion was found in tumors. The hepatic malignancy was of host origin in these mice. There was higher expression of extracellular matrix proteins and more inflammatory cells in liver tumor nodules than in regenerating normal liver nodules. Hepatocytes generated by fusion with bone marrow cells did not form malignant tumors. Extracellular matrix and inflammatory cells had significantly accumulated in liver tumors.http://dx.doi.org/10.1155/2016/5791317
spellingShingle Pei-Rong Wang
Yi Li
Cellular Origins of Regenerating Nodules and Malignancy in the FAH Model of Liver Injury after Bone Marrow Cell Transplantation
Stem Cells International
title Cellular Origins of Regenerating Nodules and Malignancy in the FAH Model of Liver Injury after Bone Marrow Cell Transplantation
title_full Cellular Origins of Regenerating Nodules and Malignancy in the FAH Model of Liver Injury after Bone Marrow Cell Transplantation
title_fullStr Cellular Origins of Regenerating Nodules and Malignancy in the FAH Model of Liver Injury after Bone Marrow Cell Transplantation
title_full_unstemmed Cellular Origins of Regenerating Nodules and Malignancy in the FAH Model of Liver Injury after Bone Marrow Cell Transplantation
title_short Cellular Origins of Regenerating Nodules and Malignancy in the FAH Model of Liver Injury after Bone Marrow Cell Transplantation
title_sort cellular origins of regenerating nodules and malignancy in the fah model of liver injury after bone marrow cell transplantation
url http://dx.doi.org/10.1155/2016/5791317
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AT yili cellularoriginsofregeneratingnodulesandmalignancyinthefahmodelofliverinjuryafterbonemarrowcelltransplantation