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Open Access Adult Human Liver Mesenchymal Stem/Progenitor Cells Participate in Mouse Liver Regeneration After Hepatectomy

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Abstract:

The advances in stem cell science have promoted research on their use in liver regenerative medicine. Beyond the demonstration of their ability to display metabolic functions in vitro, candidate cells should demonstrate achievable in situ differentiation and ability to participate to liver repopulation. In this work, we studied the in vivo behavior of adult liver mesenchymal stem/progenitor cells (ADHLSCs) after transplantation into immunodeficient mice. The kinetics of engraftment and in situ hepatogenic differentiation were analyzed. Response of transplanted ADHLSCs to regenerative stimulus was also evaluated. Nondifferentiated ADHLSCs were intrasplenically transplanted into SCID mice. Efficiency of transplantation was evaluated at the level of engraftment and in situ differentiation using immunohistochemistry, in situ hybridization, and RT-PCR. After bromodeoxyuridine (BrdU) implantation, proliferation of transplanted ADHLSCs in response to 20% hepatectomy was assessed using immunohistochemistry. We demonstrated that ADHLSC engraftment in the SCID mouse liver was low but remained stable up to 60 days posttransplantation, when albumin (ALB) immunopositive ADHLSCs were still detected and organized as clusters. Coexpression of ornithine transcarbamylase (OTC) demonstrated ADHLSC in situ differentiation mostly near the hepatic portal vein. After 20% hepatectomy on 1 month transplanted mice, the percentage of BrdU and human ALB immunopositive ADHLSCs increased from 3 to 28 days post-BrdU implantation to reach 31.3±5.4% of the total analyzed human cells. In the current study, we demonstrate that transplanted ADHLSCs are able to differentiate in the non preconditioned SCID mouse liver mainly in the periportal area. In response to partial hepatectomy, integrated ADHLSCs proliferate and participate to recipient mouse liver regeneration.

Keywords: Engraftment; Hepatocyte; In situ differentiation; Liver; Liver regeneration; Stem/progenitor cells

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368912X659853

Publication date: August 9, 2013

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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