Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Mar;56(3):405-15.
doi: 10.1136/gut.2005.090050. Epub 2006 Aug 23.

Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers

Ines Aurich  1 , Lutz P Mueller, Hendryk Aurich, Jana Luetzkendorf, Kai Tisljar, Matthias M Dollinger, Wiebke Schormann, Jens Walldorf, Jan G Hengstler, Wolfgang E Fleig, Bruno Christ
Affiliations

Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers

Ines Aurich et al. Gut. 2007 Mar.

Abstract

Aims: At present, clinical success of hepatocyte transplantation as an alternative to whole liver transplantation is hampered by the limited availability of suitable donor organs for the isolation of transplantable hepatocytes. Hence, novel cell sources are required to deliver hepatocytes of adequate quality for clinical use. Mesenchymal stem cells (MSCs) from human bone marrow may have the potential to differentiate into hepatocytes in vitro and in vivo.

Methods: Isolated MSCs were selected by density gradient centrifugation and plastic adherence, differentiated in the presence of human hepatocyte growth medium and transplanted in immunodeficient Pfp/Rag2 mice.

Results: Here, we demonstrate that human MSCs gain in vitro the characteristic morphology and function of hepatocytes in response to specified growth factors. Specifically, preconditioned MSCs store glycogen, synthesise urea and feature the active hepatocyte-specific gene promoter of phosphoenolpyruvate carboxykinase (PCK1). After transplantation into livers of immunodeficient mice, preconditioned MSCs engraft predominantly in the periportal portion of the liver lobule. In situ, the cells continue to store glycogen and express PCK1, connexin32, albumin and the human hepatocyte-specific antigen HepPar1, indicating that the transplanted cells retain prominent qualities of hepatocytes after their regional integration.

Conclusion: MSCs derived from human bone marrow may serve as a novel source for the propagation of hepatocyte-like cells suitable for cell therapy in liver diseases.

PubMed Disclaimer

Conflict of interest statement

Competing Interest: None declared.

References

    1. Fox I J, Roy‐Chowdhury J. Hepatocyte transplantation. Am J Transplant 20044(Suppl. 6)7–13. - PubMed
    1. Lee S ‐ W, Wang X, Chowdhury N R.et al Hepatocyte transplantation: state of the art and strategies for overcoming existing hurdles. Ann Hepatol 2004348–53. - PubMed
    1. Grompe M. Liver repopulation for the treatment of metabolic diseases. J Inherit Metab Dis 200124231–244. - PubMed
    1. Walldorf J, Aurich H, Cai H.et al Expanding hepatocytes in vitro before cell transplantation: donor age‐dependent proliferative capacity of cultured human hepatocytes. Scand J Gastroenterol 200439584–593. - PubMed
    1. Lagasse E, Connors H, Al‐Dhalimy M.et al Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 200061229–1234. - PubMed

Publication types

Substances