Chemokine (C-X-C motif) ligand 8 enhances the homing ability of human umbilical vein endothelial cells by promoting a paracrine response in mesenchymal stem cells under the high glucose environment

doi:10.3969/j.issn.2095-4344.2017.05.016

Abstract

Abstract:

BACKGROUND: Chemokines can promote (MSCs) the secretion of vasoactive factors from mesenchymal stem cells (MSCs) through paracrine mechanism, which have important role in accelerating angiogenesis.
OBJECTIVE: Under the high glucose environment, to the effect of the supernatant of MSCs stimulated by chemokine (C-X-C motif) ligand 8 (CXCL-8) on human umbilical vein endothelial cells (HUVECs), and to analyze the mechanism of Sonic Hedgehog signaling pathway in the stimulation of CXCL-8 on MSCs.
METHODS: Under the high glucose environment, the MSCs supplemented with 100 μg/L CXCL-8 were set as CXCL-8 group; the MSCs that were preprocessed with 5 μmol/L octyl maleimide for 45 minutes and then stimulated with 100 μg/L CXCL-8 were as Shh inhibitor group; the MSCs that were routinely cultured in a high-glucose medium were as control group. The cell supernatant of each group was extracted as conditioned medium (CM) to culture HUVECs, respectively, and these cells were referred to as CXCL-8 CM group, Shh inhibitor CM group, and control CM group, respectively. Cell counting kit-8, cell scratch and Transwell chamber tests were used to observe the effect of each CM on HUVEC proliferation, apoptosis and chemotaxis. By establishment of a diabetic skin ulcer model in C57BL/6J mice, the CM of each group was used to treat the mouse model to confirm the effects of CXCL-8 stimulated MSCs CM on HUVEC homing and ulcer healing.
RESULTS AND CONCLUSION: (1) The experimental results in vitro: compared with the control CM group, CXCL-8 CM group significantly promoted the proliferation of HUVECs, and decreased the apoptosis of HUVECs, the closure rate and migration rate of HUVECs were significantly increased (P < 0.01 or P < 0.01), and the levels of vascular endothelial growth factor and epidermal growth factor were significantly increased (P < 0.01 or P < 0.01). Compared with CXCL-8 CM group, however, the above results in the Shh inhibitor CM group showed reverse changes (P < 0.01). (2) The experimental results in vivo: compared with the MSCs CM group and Shh inhibitor CM group, the healing effect of diabetic skin ulcer and the number of HUVECs labeled by green fluorescent protein in the CXCL-8 CM group were significantly increased (P < 0.01). To conclude, these findings indicate that CXCL-8 stimulated MSCs secrete paracrine factors, vascular endothelial growth factor and epidermal growth factor, through the Sonic Hedgehog signaling pathway under the high glucose environment, which enhance the homing ability of HUVECs.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Tissue Engineering, Stem Cells, Chemotactic Factors, Diabetes Mellitus

CLC Number:

R394.2

Xie Li-ping, Zhang Shan-qiang, Sun Shi-zhu, Zhang Hai-yan, Lang Wei-ya, Zhang Meng, Shen Lei. Chemokine (C-X-C motif) ligand 8 enhances the homing ability of human umbilical vein endothelial cells by promoting a paracrine response in mesenchymal stem cells under the high glucose environment[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(5): 748-754.

Figures/Tables 3

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