Adult Human Liver Mesenchymal Stem/Progenitor Cells Participate in Mouse Liver Regeneration after Hepatectomy
The advances in stem cell science have promoted research on their use in liver regenerative medicine. Beyond the demonstration of their ability to display metabolic functions in vitro, candidate cells should demonstrate achievable in situ differentiation and ability to participate to liver repopulat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2013-08-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368912X659853 |
| _version_ | 1818415611314700288 |
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| author | Dung Ngoc Khuu Omar Nyabi Cédric Maerckx Etienne Sokal Mustapha Najimi Ph.D. |
| author_facet | Dung Ngoc Khuu Omar Nyabi Cédric Maerckx Etienne Sokal Mustapha Najimi Ph.D. |
| author_sort | Dung Ngoc Khuu |
| collection | DOAJ |
| description | The advances in stem cell science have promoted research on their use in liver regenerative medicine. Beyond the demonstration of their ability to display metabolic functions in vitro, candidate cells should demonstrate achievable in situ differentiation and ability to participate to liver repopulation. In this work, we studied the in vivo behavior of adult liver mesenchymal stem/progenitor cells (ADHLSCs) after transplantation into immunodeficient mice. The kinetics of engraftment and in situ hepatogenic differentiation were analyzed. Response of transplanted ADHLSCs to regenerative stimulus was also evaluated. Nondifferentiated ADHLSCs were intrasplenically transplanted into SCID mice. Efficiency of transplantation was evaluated at the level of engraftment and in situ differentiation using immunohistochemistry, in situ hybridization, and RT-PCR. After bromodeoxyuridine (BrdU) implantation, proliferation of transplanted ADHLSCs in response to 20% hepatectomy was assessed using immunohistochemistry. We demonstrated that ADHLSC engraftment in the SCID mouse liver was low but remained stable up to 60 days posttransplantation, when albumin (ALB) immunopositive ADHLSCs were still detected and organized as clusters. Coexpression of ornithine transcarbamylase (OTC) demonstrated ADHLSC in situ differentiation mostly near the hepatic portal vein. After 20% hepatectomy on 1 month transplanted mice, the percentage of BrdU and human ALB immunopositive ADHLSCs increased from 3 to 28 days post-BrdU implantation to reach 31.3 ± 5.4% of the total analyzed human cells. In the current study, we demonstrate that transplanted ADHLSCs are able to differentiate in the non preconditioned SCID mouse liver mainly in the periportal area. In response to partial hepatectomy, integrated ADHLSCs proliferate and participate to recipient mouse liver regeneration. |
| first_indexed | 2024-12-14T11:37:45Z |
| format | Article |
| id | doaj.art-4faa57f54386483cadccbbe85b9c559a |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-14T11:37:45Z |
| publishDate | 2013-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-4faa57f54386483cadccbbe85b9c559a2022-12-21T23:02:57ZengSAGE PublishingCell Transplantation0963-68971555-38922013-08-012210.3727/096368912X659853Adult Human Liver Mesenchymal Stem/Progenitor Cells Participate in Mouse Liver Regeneration after HepatectomyDung Ngoc Khuu0Omar Nyabi1Cédric Maerckx2Etienne Sokal3Mustapha Najimi Ph.D.4Université Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, BelgiumUniversité Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, BelgiumUniversité Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, BelgiumUniversité Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, BelgiumUniversité Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, BelgiumThe advances in stem cell science have promoted research on their use in liver regenerative medicine. Beyond the demonstration of their ability to display metabolic functions in vitro, candidate cells should demonstrate achievable in situ differentiation and ability to participate to liver repopulation. In this work, we studied the in vivo behavior of adult liver mesenchymal stem/progenitor cells (ADHLSCs) after transplantation into immunodeficient mice. The kinetics of engraftment and in situ hepatogenic differentiation were analyzed. Response of transplanted ADHLSCs to regenerative stimulus was also evaluated. Nondifferentiated ADHLSCs were intrasplenically transplanted into SCID mice. Efficiency of transplantation was evaluated at the level of engraftment and in situ differentiation using immunohistochemistry, in situ hybridization, and RT-PCR. After bromodeoxyuridine (BrdU) implantation, proliferation of transplanted ADHLSCs in response to 20% hepatectomy was assessed using immunohistochemistry. We demonstrated that ADHLSC engraftment in the SCID mouse liver was low but remained stable up to 60 days posttransplantation, when albumin (ALB) immunopositive ADHLSCs were still detected and organized as clusters. Coexpression of ornithine transcarbamylase (OTC) demonstrated ADHLSC in situ differentiation mostly near the hepatic portal vein. After 20% hepatectomy on 1 month transplanted mice, the percentage of BrdU and human ALB immunopositive ADHLSCs increased from 3 to 28 days post-BrdU implantation to reach 31.3 ± 5.4% of the total analyzed human cells. In the current study, we demonstrate that transplanted ADHLSCs are able to differentiate in the non preconditioned SCID mouse liver mainly in the periportal area. In response to partial hepatectomy, integrated ADHLSCs proliferate and participate to recipient mouse liver regeneration.https://doi.org/10.3727/096368912X659853 |
| spellingShingle | Dung Ngoc Khuu Omar Nyabi Cédric Maerckx Etienne Sokal Mustapha Najimi Ph.D. Adult Human Liver Mesenchymal Stem/Progenitor Cells Participate in Mouse Liver Regeneration after Hepatectomy Cell Transplantation |
| title | Adult Human Liver Mesenchymal Stem/Progenitor Cells Participate in Mouse Liver Regeneration after Hepatectomy |
| title_full | Adult Human Liver Mesenchymal Stem/Progenitor Cells Participate in Mouse Liver Regeneration after Hepatectomy |
| title_fullStr | Adult Human Liver Mesenchymal Stem/Progenitor Cells Participate in Mouse Liver Regeneration after Hepatectomy |
| title_full_unstemmed | Adult Human Liver Mesenchymal Stem/Progenitor Cells Participate in Mouse Liver Regeneration after Hepatectomy |
| title_short | Adult Human Liver Mesenchymal Stem/Progenitor Cells Participate in Mouse Liver Regeneration after Hepatectomy |
| title_sort | adult human liver mesenchymal stem progenitor cells participate in mouse liver regeneration after hepatectomy |
| url | https://doi.org/10.3727/096368912X659853 |
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