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Surgery. 2015 Aug;158(2):349-59. doi: 10.1016/j.surg.2015.04.014. Epub 2015 May 29.

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

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Department of Surgery, Virginia Commonwealth University, Richmond, VA.
Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA.
Department of Surgery, Mayo Clinic Jacksonville, Jacksonville, FL.
Transplant Institute, Beth Israel Deaconess Medical Center, Boston, MA. Electronic address:



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.


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.


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.


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.

[Indexed for MEDLINE]

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