Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory Death
Hepatocyte transplantation is a promising treatment for liver failure and inborn metabolic liver diseases, but progress has been hampered by a scarcity of available organs. Here, hepatocytes isolated from livers procured for a neonatal hepatocyte donation program within a research setting were asses...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2022-01-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/09636897211069900 |
| _version_ | 1828883697695195136 |
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| author | Emil Bluhme Ewa Henckel Roberto Gramignoli Therese Kjellin Christina Hammarstedt Greg Nowak Ahmad Karadagi Helene Johansson Öystein Jynge Maria Söderström Björn Fischler Stephen Strom Ewa Ellis Boubou Hallberg Carl Jorns |
| author_facet | Emil Bluhme Ewa Henckel Roberto Gramignoli Therese Kjellin Christina Hammarstedt Greg Nowak Ahmad Karadagi Helene Johansson Öystein Jynge Maria Söderström Björn Fischler Stephen Strom Ewa Ellis Boubou Hallberg Carl Jorns |
| author_sort | Emil Bluhme |
| collection | DOAJ |
| description | Hepatocyte transplantation is a promising treatment for liver failure and inborn metabolic liver diseases, but progress has been hampered by a scarcity of available organs. Here, hepatocytes isolated from livers procured for a neonatal hepatocyte donation program within a research setting were assessed for metabolic function and suitability for transplantation. Organ donation was considered for infants who died in neonatal intensive care in the Stockholm region during 2015–2021. Inclusion was assessed when a decision to discontinue life-sustaining treatment had been made and hepatectomy performed after declaration of death. Hepatocyte isolation was performed by three-step collagenase perfusion. Hepatocyte viability, yield, and function were assessed using fresh and cryopreserved cells. Engraftment and maturation of cryopreserved neonatal hepatocytes were assessed by transplantation into an immunodeficient mouse model and analysis of the gene expression of phase I, phase II, and liver-specific enzymes and proteins. Twelve livers were procured. Median warm ischemia time (WIT) was 190 [interquartile range (IQR): 80–210] minutes. Median viability was 86% (IQR: 71%–91%). Median yield was 6.9 (IQR: 3.4–12.8) x10 6 viable hepatocytes/g. Transplantation into immunodeficient mice resulted in good engraftment and maturation of hepatocyte-specific proteins and enzymes. A neonatal organ donation program including preterm born infants was found to be feasible. Hepatocytes isolated from neonatal donors had good viability, function, and engraftment despite prolonged WIT. Therefore, neonatal livers should be considered as a donor source for clinical hepatocyte transplantation, even in cases with extended WIT. |
| first_indexed | 2024-12-13T10:53:57Z |
| format | Article |
| id | doaj.art-e737b9a13ec74340b9124983e495745f |
| institution | Directory Open Access Journal |
| issn | 1555-3892 |
| language | English |
| last_indexed | 2024-12-13T10:53:57Z |
| publishDate | 2022-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-e737b9a13ec74340b9124983e495745f2022-12-21T23:49:42ZengSAGE PublishingCell Transplantation1555-38922022-01-013110.1177/09636897211069900Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory DeathEmil Bluhme0Ewa Henckel1Roberto Gramignoli2Therese Kjellin3Christina Hammarstedt4Greg Nowak5Ahmad Karadagi6Helene Johansson7Öystein Jynge8Maria Söderström9Björn Fischler10Stephen Strom11Ewa Ellis12Boubou Hallberg13Carl Jorns14Department of Transplantation, Karolinska University Hospital, Stockholm, SwedenDepartment of Neonatology, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, SwedenDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, SwedenDepartment of Neonatology, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, SwedenDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, SwedenDepartment of Transplantation, Karolinska University Hospital, Stockholm, SwedenDepartment of Transplantation, Karolinska University Hospital, Stockholm, SwedenDepartment of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institutet, Stockholm, SwedenOrganisation for Organ Donation in Central Sweden, Stockholm, SwedenOrganisation for Organ Donation in Central Sweden, Stockholm, SwedenDepartment of Pediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, SwedenDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, SwedenDepartment of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institutet, Stockholm, SwedenDepartment of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institutet, Stockholm, SwedenDepartment of Transplantation, Karolinska University Hospital, Stockholm, SwedenHepatocyte transplantation is a promising treatment for liver failure and inborn metabolic liver diseases, but progress has been hampered by a scarcity of available organs. Here, hepatocytes isolated from livers procured for a neonatal hepatocyte donation program within a research setting were assessed for metabolic function and suitability for transplantation. Organ donation was considered for infants who died in neonatal intensive care in the Stockholm region during 2015–2021. Inclusion was assessed when a decision to discontinue life-sustaining treatment had been made and hepatectomy performed after declaration of death. Hepatocyte isolation was performed by three-step collagenase perfusion. Hepatocyte viability, yield, and function were assessed using fresh and cryopreserved cells. Engraftment and maturation of cryopreserved neonatal hepatocytes were assessed by transplantation into an immunodeficient mouse model and analysis of the gene expression of phase I, phase II, and liver-specific enzymes and proteins. Twelve livers were procured. Median warm ischemia time (WIT) was 190 [interquartile range (IQR): 80–210] minutes. Median viability was 86% (IQR: 71%–91%). Median yield was 6.9 (IQR: 3.4–12.8) x10 6 viable hepatocytes/g. Transplantation into immunodeficient mice resulted in good engraftment and maturation of hepatocyte-specific proteins and enzymes. A neonatal organ donation program including preterm born infants was found to be feasible. Hepatocytes isolated from neonatal donors had good viability, function, and engraftment despite prolonged WIT. Therefore, neonatal livers should be considered as a donor source for clinical hepatocyte transplantation, even in cases with extended WIT.https://doi.org/10.1177/09636897211069900 |
| spellingShingle | Emil Bluhme Ewa Henckel Roberto Gramignoli Therese Kjellin Christina Hammarstedt Greg Nowak Ahmad Karadagi Helene Johansson Öystein Jynge Maria Söderström Björn Fischler Stephen Strom Ewa Ellis Boubou Hallberg Carl Jorns Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory Death Cell Transplantation |
| title | Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory Death |
| title_full | Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory Death |
| title_fullStr | Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory Death |
| title_full_unstemmed | Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory Death |
| title_short | Procurement and Evaluation of Hepatocytes for Transplantation From Neonatal Donors After Circulatory Death |
| title_sort | procurement and evaluation of hepatocytes for transplantation from neonatal donors after circulatory death |
| url | https://doi.org/10.1177/09636897211069900 |
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