Human mesenchymal stem cells are recruited to injured liver in a β1-integrin and CD44 dependent manner (Hepatology, 2012, 56:1063-1073)

報告日期: 2012/10/16
報告時間: 15:10/16:00
報告學生: 王筱涵 (英文報告)
講評老師: 楊倍昌
附件下載: 下載[1218-1348566389-1.pdf] 

 

Human Mesenchymal Stem Cells Are Recruited to Injured Liver in a β1-Integrin and CD44 Dependent Manner

 

Aldridge V, Garg A, Davies N, Bartlett DC, Youster J, Beard H, Kavanagh DP, et al.

 

Hepatology. 2012 Sep;56(3):1063-73.

 

Speaker:Hsiao-Han Wang (王筱涵)                        Date: 2012, 10, 16

 

Commentator:Bei-Chang Yang (楊倍昌) Ph.D                Place: Room 602

 

Abstract

Human mesenchymal stem cells (hMSCs) have self-renewal capability and the potential to differentiate into cell lineages of mesenchymal tissues. Some studies revealed that hMSCs contributed totherapy for liver disease including differentiation into hepatocytes and down-regulate immune mediated liver damage. The delivery of hMSCs to injured organs is important in the mediation of their effect. In order to understand the mechanisms regulating hMSCs egress into liver, the author investigated the adhesion molecules expression profile of hMSC, then used the antibody to neutralizethese adhesion molecules and quantified the number of hMSCs which bind to liver tissue, extracellular matrices, and human hepatic sinusoidal endothelial cells (HSECs) in static and flow conditions.Authors found the number of hMSCs adhesion was higher in diseased liver and TNFα / IFNγ treated HSEC. This adhesion was disrupted by blocked the CD29/β1-integrin and CD44 expression level which were highly expressed in hMSCs. Under flow condition, hMSCs only rolled on vascular cell adhesion molecule-1 (VCAM-1), this rolling was abolished by blockage CD29 of hMSCs and VCAM-1 of HSECs, but both of CD29 and CD44 blockage was able to reduce the firm adhesion. To confirm the hepatic engraftment of hMSCs in vivo, CFSE-labelled hMSCs were intraportally injected into CCl4–injured mice. Both of CD29 and CD44 blockage reduced the number of hMSCs engraft in murine liver. Although hMSCs expressed some chemokine receptors including CCR4, CCR5 and CXCR3, and could migrate to specific chemokines, but interrupted these chemokine receptors did not affect hMSCs adhesion. This study identified CD29 and CD44 may act promising candidates that may be improve the efficiency of cellular therapy by control delivery and retention of hMSCs within the liver.

 

Reference

1.      Kuo TK, Hung SP, Chuang CH, Chen CT, Shih YR, Fang SC, Yang VW and Lee OK. (2008) Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology. 134(7):2111-21, 2121.e1-3.

 

2.      Forbes SJ and Newsome PN.(2012) New horizons for stem cell therapy in liver disease. JHepatol. 56(2):496-9.