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. 2019 Jan 30;68(11):2044–2056. doi: 10.1136/gutjnl-2018-316091

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© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Characterisation of human bone marrow mesenchymal stem cell (hBMSC)-derived hepatocytes in hBMSC-Fah^-/- Rag2^-/- IL-2Rγc^-/-SCID (FRGS) mice. (A) Detection of the serum human albumin (hALB) level and percentage of human leucocyte antigen-positive (HLA⁺) cells in the total population of liver cells (n=8/group). (B) Percentage of hALB⁺, hNTCP⁺ and hCD45⁺ cells in the HLA⁺ cells from week 0 to 60 after hBMSC transplantation (n=8/group). (C) Correlation analysis between the serum hALB level and the percentage of hNTCP⁺ cells in the whole population of liver cells collected from hBMSC-FRGS mice (n=8/group). (D) Morphology of fluorescent-activated cell sorting (FACS)-sorted hALB⁺ hBMSC-hepatocytes (Heps) at week 12 after transplantation (bar=50 µm). (E) Detection of perfused hBMSC-Heps by immunofluorescence (IF) staining for hALB and hNTCP at week 12 after transplantation (bar=50 µm). (F) Quantitative reverse transcription PCR (qRT-PCR) analysis of the expression of 19 hepatic genes in the perfused hBMSC-Heps from week 12 to 60 after transplantation; primary human hepatocytes and hBMSCs were used as controls (n=6/group). (G) Immunohistochemistry (IHC) staining of liver tissues collected from hBMSC-FRGS mice at week 12 after transplantation for human hepatocyte markers, including hALB, hCK18, hAAT, hFAH and hNTCP (bar=100 µm). (H) IHC staining for hALB⁺ hBMSC-Heps in the whole liver lobe showed multiple distribution patterns, including periportal, non-periportal, scatter-like, island-like and cluster-like patterns (bar=1 mm). hFAH, human hepatocyte-specific fumarate dehydrogenase; hAAT, human hepatocyte-specific alpha-1-antitrypsin; hCK18, human hepatocyte-specific cytokeratin 18; hNTCP, human sodium-sodium taurocholate co-transporting polypeptide.