Abstract

The migration of administered mesenchymal stem cells (MSCs) to sites of injury via the bloodstream has been demonstrated. However, the underlying mechanisms of umbilical cord MSC adhesion to endothelial cells during transendothelial migration are still unclear. In this study, our data showed that IL-1β induced LFA-1 expression on MSCs and ICAM-1 expression on HUVECs. We then pretreated MSCs with protein synthesis inhibitor cycloheximide. The results showed that IL-1β induced LFA-1 expression on the surface of MSCs via the protein synthesis pathway. Through the p38 MAPK signaling pathway inhibitor SB 203580, we found that IL-1β induces the expression of LFA-1 through p38 MAPK signaling and enhances ICAM-1 expression in HUVECs. In addition, IL-1β-induced MSC adhesion to HUVECs was found to be inhibited by IL-1RA and the LFA-1 inhibitor lovastatin. These results indicate that IL-1β promotes the cell adhesion of MSCs to HUVECs through LFA-1/ICAM-1 interaction. We address the evidence that the cell adhesion mechanism of IL-1β promotes MSC adhesion to HUVECs. The implications of these findings could enhance the therapeutic potential of MSCs.

Highlights

  • Umbilical cord mesenchymal stem cells (UC-MSCs) are multipotent cells with the capacity for self-renewal and differentiation into cells of the cardiomyogenic, adipogenic, and osteogenic lineages [1]

  • We show that MSC adhesion to human umbilical vein endothelial cell (HUVEC) is induced by IL-1β

  • MSCs were treated with 100 ng/ml IL-1β for 15, 30, 120, and 360 minutes to induce Lymphocyte function-associated antigen 1 (LFA-1) expression

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Summary

Introduction

Umbilical cord mesenchymal stem cells (UC-MSCs) are multipotent cells with the capacity for self-renewal and differentiation into cells of the cardiomyogenic, adipogenic, and osteogenic lineages [1]. MSCs have the ability to secrete paracrine factors and to home in on sites of inflammation following tissue injury in a mouse model [2,3,4]. Previous research has shown that treatment strategies such as pretreatment with cytokines or growth factors may improve MSC migration and adhesion [5, 6]. IL-1β is a highly inflammatory cytokine produced when tissue is inflamed due to the presence of monocytes and macrophages [7]. They are secreted and circulated systemically [8]. We found that interleukin-1β (IL-1β) induced mesenchymal stem cell migration in vitro [9, 10]. IL-1β induced ICAM-1 expression in human umbilical vein endothelial cell (HUVEC) [13], ICAM-1, and VCAM-1 expression in human vascular smooth muscle cells [14]

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