Adult Human Liver Mesenchymal Stem/Progenitor Cells Participate in Mouse Liver Regeneration after Hepatectomy

Cell Transplantation

Article

Etienne Sokal¹  Omar Nyabi¹  Dung Ngoc Khuu¹  Mustapha Najimi¹  Cédric Maerckx¹ 

[1] Université Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, Belgium;

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

DOI  :  10.3727/096368912X659853

 received in 2011-06-22, accepted in 2012-08-15,  发布年份 2013

来源: Sage Journals

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2013 Cognizant Comm. Corp.

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