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Transplanted human pluripotent stem cell-derived mesenchymal stem cells support liver regeneration in Gunn rats

Transplanted human pluripotent stem cell-derived mesenchymal stem cells support liver regeneration in Gunn rats
Transplanted human pluripotent stem cell-derived mesenchymal stem cells support liver regeneration in Gunn rats
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.
1547-3287
Oreffo, Richard
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Spitzhorn, Lucas-Sebastian
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Kordes, Claus
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Megges, M.
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Sawitza, Iris
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Gotze, Silke
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Reichert, D
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Schulze-Matz, Peggy
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Graffmann, Nina
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Bohndorf, Martina
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Wruck, Wasco
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Kohler, J
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Herebian, Diran
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Mayatepek, Ertan
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Haussinger, Dieter
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Adjaye, James
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Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Spitzhorn, Lucas-Sebastian
9c868474-9ef0-40eb-91e8-ab85b34b2016
Kordes, Claus
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Megges, M.
724e45bf-6f8d-4ae9-8bc7-da0e14bbee18
Sawitza, Iris
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Gotze, Silke
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Reichert, D
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Schulze-Matz, Peggy
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Graffmann, Nina
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Bohndorf, Martina
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Wruck, Wasco
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Kohler, J
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Herebian, Diran
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Mayatepek, Ertan
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Haussinger, Dieter
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Adjaye, James
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Oreffo, Richard, Spitzhorn, Lucas-Sebastian, Kordes, Claus, Megges, M., Sawitza, Iris, Gotze, Silke, Reichert, D, Schulze-Matz, Peggy, Graffmann, Nina, Bohndorf, Martina, Wruck, Wasco, Kohler, J, Herebian, Diran, Mayatepek, Ertan, Haussinger, Dieter and Adjaye, James (2018) Transplanted human pluripotent stem cell-derived mesenchymal stem cells support liver regeneration in Gunn rats. Stem Cells and Development, 27 (24). (doi:10.1089/scd.2018.0010).

Record type: Article

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.

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Spitzhorn_etal.2018 - Accepted Manuscript
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Accepted/In Press date: 29 September 2018
e-pub ahead of print date: 7 December 2018
Published date: December 2018

Identifiers

Local EPrints ID: 426976
URI: http://eprints.soton.ac.uk/id/eprint/426976
ISSN: 1547-3287
PURE UUID: 8dbcbe8b-0bd6-49a4-9893-b99ff6ac8cd8
ORCID for Richard Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

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Date deposited: 19 Dec 2018 17:30
Last modified: 07 Oct 2020 04:33

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