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Stem Cells Dev. 2018 Nov 20. doi: 10.1089/scd.2018.0010. [Epub ahead of print]

Transplanted Human Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Support Liver Regeneration in Gunn Rats.

Author information

1
1 Institute for Stem Cell Research and Regenerative Medicine, Neonatolgy and Pediatric Cardiology, Heinrich Heine University , Düsseldorf, Germany .
2
2 Clinic of Gastroenterology, Hepatology and Infectious Diseases, and Neonatolgy and Pediatric Cardiology, Heinrich Heine University , Düsseldorf, Germany .
3
3 Department of General Pediatrics, Neonatolgy and Pediatric Cardiology, Heinrich Heine University , Düsseldorf, Germany .
4
4 Centre for Human Development, Stem Cells and Regeneration, Faculty of Medicine, University of Southampton , Southampton, United Kingdom .

Abstract

Gunn rats bear a mutation within the uridine diphosphate glucuronosyltransferase-1a1 (Ugt1a1) gene resulting in high serum bilirubin levels as seen in Crigler-Najjar syndrome. In this study, the Gunn rat was used as an animal model for heritable liver dysfunction. Induced mesenchymal stem cells (iMSCs) derived from embryonic stem cells (H1) and induced pluripotent stem cells were transplanted into Gunn rats after partial hepatectomy. The iMSCs engrafted and survived in the liver for up to 2 months. The transplanted iMSCs differentiated into functional hepatocytes as evidenced by partially suppressed hyperbilirubinemia and expression of multiple human-specific hepatocyte markers such as albumin, hepatocyte nuclear factor 4α, UGT1A1, cytokeratin 18, bile salt export pump, multidrug resistance protein 2, Na/taurocholate-cotransporting polypeptide, and α-fetoprotein. These findings imply that transplanted human iMSCs can contribute to liver regeneration in vivo and thus represent a promising tool for the treatment of inherited liver diseases.

KEYWORDS:

ESC; fetal MSC; iMSC; iPSC; liver regeneration; stem cell transplantation

PMID:
30280963
DOI:
10.1089/scd.2018.0010

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