LFA-1 and VLA-4 involved in human high proliferative potentialendothelial progenitor cells homing to ischemic tissue

Huaxin Duan; Lamei Cheng; Xuan Sun; Yonggang Wu; Liangshan Hu; Jian Wang; Huiping Zhao; Guangxiu Lu

doi:10.1160/TH06-04-0199

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2006; 96(06): 807-815
DOI: 10.1160/TH06-04-0199

Endothelium and Vascular Development

Schattauer GmbH

LFA-1 and VLA-4 involved in human high proliferative potentialendothelial progenitor cells homing to ischemic tissue

Huaxin Duan

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China

,

Lamei Cheng

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China

,

Xuan Sun

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China

,

Yonggang Wu

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China

,

Liangshan Hu

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China

,

Jian Wang

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China

,

Huiping Zhao

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China

,

Guangxiu Lu

¹National Center of Human Stem Cell Research and Engineering, Institute of Human Reproduction and Stem Cell Engineering, Central South University, Changsha, China

› Institutsangaben

Abstract

Summary

Cumulative evidences have revealed that endothelial progenitor cell (EPC) transplantation can promote the neovascularization in ischemic tissue, but the mechanism of EPCs homing to the site of ischemia is poorly understood. In this study, to investigate the mechanism of human umbilical cord blood-derived high proliferative potential-endothelial progenitor cells (HPP-EPCs) homing to ischemic tissue we evaluated the expression of lymphocyte function-associated antigen-1 (LFA-1, or CD11a/CD18) and very late antigen-4 (VLA-4, or CD49d/CD29) in EPCs and the changes of expression level of their ligands, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), in ischemic tissue and performed the adhesion and migration assays to analyze the interaction between the receptors and ligands. Furthermore, we studied the roles of LFA-1 and VLA-4 in EPC homing in an ischemic model of mice. The results show that LFA-1 andVLA-4 were expressed in HPPEPCs and ICAM-1 and VCAM-1 were expressed in vessel endothelium in ischemic tissues. The pre-incubation of HPP-EPCs with neutralizing antibodies against CD11a or CD49d reduced adhesion and migration of HPP-EPCs in vitro and reduced recovery of hind-limb blood flow, capillary density and incorporation of HPP-EPC into ischemic tissues in vivo. Furthermore, the pre-incubation of HPP-EPCs with the combination of CD11a and CD49d antibodies led to synergistically negative effects on adhesion and transmigration of HPP-EPCs in vitro, and on the homing of HPP-EPCs to ischemic tissue and on neovascularization capacity in vivo. These results indicate that LFA-1 andVLA-4 are involved in HPP-EPC homing to ischemic tissues.

Keywords

Endothelial progenitor cells - homing - ischemia - adhesion molecules

Volltext

Referenzen

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