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...

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Published in:	Cell transplantation Vol. 31; p. 9636897211069900
Main Authors:	Bluhme, Emil, Henckel, Ewa, Gramignoli, Roberto, Kjellin, Therese, Hammarstedt, Christina, Nowak, Greg, Karadagi, Ahmad, Johansson, Helene, Jynge, Öystein, Söderström, Maria, Fischler, Björn, Strom, Stephen, Ellis, Ewa, Hallberg, Boubou, Jorns, Carl
Format:	Journal Article
Language:	English
Published:	Los Angeles, CA SAGE Publications 01-01-2022 Sage Publications Ltd SAGE Publishing
Subjects:	Animals Blood & organ donations Collagen Collagenase Cryopreservation Donors Enzymes Gene expression Hepatectomy Hepatocytes Hepatocytes - metabolism Humans Immunodeficiency Infant, Newborn Infants Ischemia Liver - metabolism Liver diseases Liver Transplantation - methods Medicin och hälsovetenskap Metabolism Mice Neonates Original Tissue and Organ Procurement Tissue Donors Transplantation Viability neonatal organ donation warm ischemia time FRGN mice
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Summary:	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) x106 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Shared first and last authors.
ISSN:	0963-6897 1555-3892 1555-3892
DOI:	10.1177/09636897211069900