Human umbilical cord mesenchymal stem cells regulate CD54 and CD105 in vascular endothelial cells and suppress inflammation in Kawasaki disease

Abstract

Objective: The objective was to evaluate the expression levels of CD31⁺CD54⁺ and CD31⁺CD105⁺ endothelial microparticles (EMPs) before and after intravenous immunoglobulin (IVIG) treatment of Kawasaki disease (KD). To explore the role of human umbilical cord mesenchymal stem cells (hucMSCs) in inhibiting endothelial inflammation in KD, the effects of hucMSCs on the expression of CD54 and CD105 in endothelial cells in KD were analyzed in vivo and in vitro.

Methods: The concentrations of IL-1β and VEGF in the peripheral blood of KD or healthy children were detected, and the distributions of CD31⁺CD54⁺ and CD31⁺CD105⁺ EMPs in platelet-poor plasma (PPP) were analyzed by flow cytometry. Human umbilical vein endothelial cells (HUVECs) were first cocultured with the patients' peripheral blood mononuclear cells (PBMCs). Next, HUVECs were cocultured with hucMSCs after stimulation with inactivated serum from patients. Cell proliferation and migration activities were assessed, and the expression of CD54, CD105 and IL-1β was analyzed. In an in vivo study, hucMSCs were transplanted into KD mice. The locations and expression levels of CD54, CD105 and IL-1β in the heart tissues of mice were analyzed.

Results: The levels of IL-1β and CD31⁺CD54⁺ EMPs were significantly higher before IVIG treatment and 2 weeks after treatment in KD patients (P < 0.01). However, the levels of VEGF and CD31⁺CD105⁺ EMPs increased significantly in KD only after IVIG treatment (P < 0.01). KD-inactivated serum stimulation combined with cocultivation of PBMCs can activate inflammation in HUVECs, leading to reduced cell proliferation and migration activities. Cocultivation also increased the expression of CD54 and decreased the expression of CD105 (P < 0.001). Cocultivation with hucMSCs can reverse these changes. Additionally, hucMSC transplantation downregulated the expression of IL-1β and CD54 and significantly upregulated the expression of CD105 in KD mice.

Conclusion: The expression levels of CD31⁺CD54⁺ and CD31⁺CD105⁺ EMPs showed inconsistent changes at different KD statuses, providing potential markers for clinical application. HucMSCs suppress inflammation and regulate the expression levels of CD54 and CD105 in vascular endothelial cells in KD, possibly providing a new basis for stem cell therapy for KD.

Keywords: Endothelial microparticles; Human umbilical cord mesenchymal stem cells; Kawasaki disease; Stem cell therapy.