Transplantation of human stem cell-derived hepatocytes in an animal model of acute liver failure

Introduction Hepatocyte cell transplantation can be life-saving in patients with acute liver failure (ALF); however, primary human hepatocyte transplantation is limited by the scarcity of donor hepatocytes. We investigated the effect of stem cell-derived, hepatocyte-like cells in an animal xenotrans...

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Bibliographic Details
Published in:Surgery 2015-08, Vol.158 (2), p.349-359
Main Authors: Ramanathan, Rajesh, MD, Pettinato, Giuseppe, PhD, Beeston, John T., RN, Lee, David D., MD, Wen, Xuejun, MD, PhD, Mangino, Martin J., PhD, Fisher, Robert A., MD
Format: Article
Language:English
Subjects:
Albumins - metabolism
Animals
Biomarkers - blood
Cell Transplantation - methods
Cells, Cultured
Hepatocytes - transplantation
Humans
Liver Failure, Acute - blood
Liver Failure, Acute - therapy
Male
Mesenchymal Stromal Cells
Rats
Rats, Nude
Surgery
Transplantation, Heterologous - methods
Treatment Outcome
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Summary:Introduction Hepatocyte cell transplantation can be life-saving in patients with acute liver failure (ALF); however, primary human hepatocyte transplantation is limited by the scarcity of donor hepatocytes. We investigated the effect of stem cell-derived, hepatocyte-like cells in an animal xenotransplant model of ALF. Methods Intraperitoneal d -galactosamine was used to develop a lethal model of ALF in the rat. Human induced pluripotent stem cells (iPSC), human mesenchymal stem cells, and human iPSC combined with human endothelial cells (iPSC + EC) were differentiated into hepatocyte-like cells and transplanted into the spleens of athymic nude rats with ALF. Results A reproducible lethal model of ALF was achieved with nearly 90% death within 3 days. Compared with negative controls, rats transplanted with stem cell-derived, hepatocyte-like cells were associated with increased survival. Human albumin was detected in the rat serum 3 days after transplantation in more than one-half the animals transplanted with hepatocyte-like cells. Only animals transplanted with iPSC + EC-derived hepatocytes had serum human albumin at 14 days posttransplant. Transplanted hepatocyte-like cells homed to the injured rat liver, whereas the ECs were only detected in the spleen. Conclusion Transplantation of stem cell-derived, hepatocyte-like cells improved survival with evidence of in vivo human albumin production. Combining ECs may prolong cell function after transplantation.
ISSN:0039-6060
1532-7361
DOI:10.1016/j.surg.2015.04.014