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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.

Author information

1
Department of Surgery, Virginia Commonwealth University, Richmond, VA.
2
Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA.
3
Department of Surgery, Mayo Clinic Jacksonville, Jacksonville, FL.
4
Transplant Institute, Beth Israel Deaconess Medical Center, Boston, MA. Electronic address: rafisher@bidmc.harvard.edu.

Abstract

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.

PMID:
26032830
DOI:
10.1016/j.surg.2015.04.014
[Indexed for MEDLINE]

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