Liver Repopulation after Hepatocellular Transplantation: Integration and Interaction of Transplanted Hepatocytes in the Host
The mechanisms of donor hepatocyte integration into recipient liver are not fully understood. We investigated mechanisms of both the integration and interaction of transplanted hepatocytes with host liver cells as well as the repopulation of the host organ following intraportal transplantation. Matu...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2005-01-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/000000005783983322 |
| _version_ | 1818203355808268288 |
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| author | Sarah Koenig Claudia Stoesser Petra Krause Heinz Becker Peter M. Markus |
| author_facet | Sarah Koenig Claudia Stoesser Petra Krause Heinz Becker Peter M. Markus |
| author_sort | Sarah Koenig |
| collection | DOAJ |
| description | The mechanisms of donor hepatocyte integration into recipient liver are not fully understood. We investigated mechanisms of both the integration and interaction of transplanted hepatocytes with host liver cells as well as the repopulation of the host organ following intraportal transplantation. Mature hepatocytes were injected into the portal vein of dipeptidylpeptidase IV (DPPIV)-deficient rats pretreated with retrorsine and subjected to 30% partial hepatectomy to ensure selective donor growth. The degree of integration and proliferation was studied by colocalizing transplanted cells (DPPIV positive) with connexin 32, MMP-2, and OX-43 (multilayer immunofluorescence imaging). FACS analysis was established to assess the extent of repopulation quantitatively. Transplanted hepatocytes reached the distal portal spaces and sinusoids within 1 h after injection. A small proportion of cells succeeded in traversing the endothelial barrier through mechanical disruption in both locations. Transplanted hepatocytes lost their membrane-bound gap junctions (connexin 32) during this process. Successful integration of the donor cells required up to 5 days, heralded by gap junction reconstitution and the specific basolateral membrane expression of DPPIV. MMP-2 degraded the extracellular matrix in close proximity to donor cells, providing space for cell division. FACS analysis revealed that more than 37% of the liver was repopulated by cells derived from donors at 2 months after transplantation. Our data demonstrate a high degree of donor cell repopulation of the host organ and provide valuable insight into the specific mechanisms of donor cell integration. Connexin 32 expression in transplanted hepatocytes may serve as an indicator of their effective incorporation and communication within the recipient liver. FACS analysis reveals an accurate method to determine quantitatively the extent of liver repopulation. |
| first_indexed | 2024-12-12T03:24:02Z |
| format | Article |
| id | doaj.art-d889dba8a7054c4fbcc8096b396588b1 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-12T03:24:02Z |
| publishDate | 2005-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-d889dba8a7054c4fbcc8096b396588b12022-12-22T00:40:06ZengSAGE PublishingCell Transplantation0963-68971555-38922005-01-011410.3727/000000005783983322Liver Repopulation after Hepatocellular Transplantation: Integration and Interaction of Transplanted Hepatocytes in the HostSarah Koenig0Claudia Stoesser1Petra Krause2Heinz Becker3Peter M. Markus4Department of General Surgery, Georg-August-University Goettingen, 37099 GermanyDepartment of General Surgery, Georg-August-University Goettingen, 37099 GermanyDepartment of General Surgery, Georg-August-University Goettingen, 37099 GermanyDepartment of General Surgery, Georg-August-University Goettingen, 37099 GermanyDepartment of General Surgery, Georg-August-University Goettingen, 37099 GermanyThe mechanisms of donor hepatocyte integration into recipient liver are not fully understood. We investigated mechanisms of both the integration and interaction of transplanted hepatocytes with host liver cells as well as the repopulation of the host organ following intraportal transplantation. Mature hepatocytes were injected into the portal vein of dipeptidylpeptidase IV (DPPIV)-deficient rats pretreated with retrorsine and subjected to 30% partial hepatectomy to ensure selective donor growth. The degree of integration and proliferation was studied by colocalizing transplanted cells (DPPIV positive) with connexin 32, MMP-2, and OX-43 (multilayer immunofluorescence imaging). FACS analysis was established to assess the extent of repopulation quantitatively. Transplanted hepatocytes reached the distal portal spaces and sinusoids within 1 h after injection. A small proportion of cells succeeded in traversing the endothelial barrier through mechanical disruption in both locations. Transplanted hepatocytes lost their membrane-bound gap junctions (connexin 32) during this process. Successful integration of the donor cells required up to 5 days, heralded by gap junction reconstitution and the specific basolateral membrane expression of DPPIV. MMP-2 degraded the extracellular matrix in close proximity to donor cells, providing space for cell division. FACS analysis revealed that more than 37% of the liver was repopulated by cells derived from donors at 2 months after transplantation. Our data demonstrate a high degree of donor cell repopulation of the host organ and provide valuable insight into the specific mechanisms of donor cell integration. Connexin 32 expression in transplanted hepatocytes may serve as an indicator of their effective incorporation and communication within the recipient liver. FACS analysis reveals an accurate method to determine quantitatively the extent of liver repopulation.https://doi.org/10.3727/000000005783983322 |
| spellingShingle | Sarah Koenig Claudia Stoesser Petra Krause Heinz Becker Peter M. Markus Liver Repopulation after Hepatocellular Transplantation: Integration and Interaction of Transplanted Hepatocytes in the Host Cell Transplantation |
| title | Liver Repopulation after Hepatocellular Transplantation: Integration and Interaction of Transplanted Hepatocytes in the Host |
| title_full | Liver Repopulation after Hepatocellular Transplantation: Integration and Interaction of Transplanted Hepatocytes in the Host |
| title_fullStr | Liver Repopulation after Hepatocellular Transplantation: Integration and Interaction of Transplanted Hepatocytes in the Host |
| title_full_unstemmed | Liver Repopulation after Hepatocellular Transplantation: Integration and Interaction of Transplanted Hepatocytes in the Host |
| title_short | Liver Repopulation after Hepatocellular Transplantation: Integration and Interaction of Transplanted Hepatocytes in the Host |
| title_sort | liver repopulation after hepatocellular transplantation integration and interaction of transplanted hepatocytes in the host |
| url | https://doi.org/10.3727/000000005783983322 |
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