PMID- 34822812 OWN - NLM STAT- MEDLINE DCOM- 20211227 LR - 20211227 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 409 IP - 2 DP - 2021 Dec 15 TI - Human umbilical cord mesenchymal stem cells regulate CD54 and CD105 in vascular endothelial cells and suppress inflammation in Kawasaki disease. PG - 112941 LID - S0014-4827(21)00497-3 [pii] LID - 10.1016/j.yexcr.2021.112941 [doi] AB - 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-1beta 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-1beta was analyzed. In an in vivo study, hucMSCs were transplanted into KD mice. The locations and expression levels of CD54, CD105 and IL-1beta in the heart tissues of mice were analyzed. RESULTS: The levels of IL-1beta 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-1beta 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. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Chen, Tao AU - Chen T AD - Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China; Research Institute of Comparative Medicine, Nantong University, Nantong, 226001, Jiangsu Province, China. FAU - Xu, Ting AU - Xu T AD - Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China; Research Institute of Comparative Medicine, Nantong University, Nantong, 226001, Jiangsu Province, China. FAU - Cheng, Mingye AU - Cheng M AD - Department of Pediatrics, Zhongda Hospital Southeast University, Nanjing, 210009, Jiangsu Province, China. FAU - Fang, Hao AU - Fang H AD - Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China. FAU - Shen, Xianjuan AU - Shen X AD - Department of Clinical Laboratory, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China. FAU - Tang, Zhiyuan AU - Tang Z AD - Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China. Electronic address: tina2951@sina.com. FAU - Zhao, Jianmei AU - Zhao J AD - Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China. Electronic address: zjmheart@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211122 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Biomarkers) RN - 0 (Endoglin) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Animals MH - Biomarkers/metabolism MH - Case-Control Studies MH - Cell Differentiation MH - Child, Preschool MH - Disease Models, Animal MH - Endoglin/*metabolism MH - Female MH - Human Umbilical Vein Endothelial Cells/immunology/*metabolism MH - Humans MH - Intercellular Adhesion Molecule-1/*metabolism MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/*cytology MH - Mice MH - Mice, Inbred C57BL MH - Mucocutaneous Lymph Node Syndrome/complications/metabolism/pathology/*therapy MH - Prognosis MH - Umbilical Cord/*cytology MH - Vasculitis/etiology/pathology/*prevention & control OTO - NOTNLM OT - Endothelial microparticles OT - Human umbilical cord mesenchymal stem cells OT - Kawasaki disease OT - Stem cell therapy EDAT- 2021/11/26 06:00 MHDA- 2021/12/28 06:00 CRDT- 2021/11/25 20:10 PHST- 2021/07/18 00:00 [received] PHST- 2021/11/15 00:00 [revised] PHST- 2021/11/18 00:00 [accepted] PHST- 2021/11/26 06:00 [pubmed] PHST- 2021/12/28 06:00 [medline] PHST- 2021/11/25 20:10 [entrez] AID - S0014-4827(21)00497-3 [pii] AID - 10.1016/j.yexcr.2021.112941 [doi] PST - ppublish SO - Exp Cell Res. 2021 Dec 15;409(2):112941. doi: 10.1016/j.yexcr.2021.112941. Epub 2021 Nov 22.