Journal
STEM CELLS AND DEVELOPMENT
Volume 27, Issue 24, Pages 1702-1714Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2018.0010
Keywords
ESC; iPSC; iMSC; stem cell transplantation; liver regeneration; fetal MSC
Funding
- German Research Foundation (DFG) through the Collaborative Research Center SFB 974 (Communication and Systems Relevance during Liver Injury and Regeneration,'' Dusseldorf)
- Federal Ministry of Education and Research-BMBF [01GN1005]
- Medical Faculty, Heinrich-Heine-University, Dusseldorf
- BBSRC [LO21072/1]
- MRC [MR/K026682/1]
- BBSRC [BB/L021072/1] Funding Source: UKRI
- MRC [MR/K026682/1] Funding Source: UKRI
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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 4 alpha, UGT1A1, cytokeratin 18, bile salt export pump, multidrug resistance protein 2, Na/taurocholate-cotransporting polypeptide, and alpha-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.
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