Effect of HMGB1 on the Paracrine Action of EPC Promotes Post-Ischemic Neovascularization in Mice. (15th September 2014)

• Record Type: Journal Article
• Authors: Chen, Chao; Lin, Xiaojie; Wang, Jixian; Tang, Guanghui; Mu, Zhihao; Chen, Xiaoyan; Xu, Jin; Wang, Yongting; Zhang, Zhijun; Yang, Guo-Yuan
• Is Part Of: Stem cells. Volume 32:Number 10(2014:Oct.)
• Page Start: 2679
• Page End: 2689
• Publication Date: 2014-09-15
• Subjects: Endothelial progenitor cell -- High mobility group box1 -- Microglia -- Neovascularization -- Stroke; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1754
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Transplantation of endothelial progenitor cells (EPCs) leads to better outcomes in experimental stroke, but the mechanism remains unclear. It was reported that astrocytic-high mobility group box1 (HMGB1) promoted endogenous EPC-mediated neurovascular remodeling during stroke recovery. It is unclear whether HMGB1 involves in exogenous EPC-mediated stroke recovery. In this study, we aim to explore whether microglial HMGB1 contributes to human peripheral blood-derived ( h PB)-EPCs-mediated neurovascular remodeling by modulating the paracrine function of exogenous h PB-EPCs. Coculturing h PB-EPCs with lipopolysaccharides stimulated BV2 cells upregulated Interleukin-8 expression in h PB-EPCs; this was blocked by treating BV2 cells with HMGB1 inhibitor Glycyrrhizin. Conditioned medium (CM) of h PB-EPCs cocultured with BV2 cells promoted the viability and tube formation of human umbilical cord vein cells. Inhibiting either HMGB1 or IL-8 could block the effect of h PB-EPCs CM. In vivo study showed h PB-EPCs transplantation improved neurobehavioral outcomes, reduced brain atrophy volume, and enhanced neovascularization in transient middle cerebral artery occlusion (tMCAO) mice. Intraperitoneally administration of HMGB1 inhibitor glycyrrhizin blocked the beneficial effect of h PB-EPC transplantation. We did not observe the integration of green fluorescent protein-labeled h PB-EPCs with microvessels in peri-infarct areas at day-14 after tMCAO. In summary, the result suggested that HMGB1 upregulation in postischemic brain could promote exogenous h PB-EPC-mediated stroke recovery by modulating paracrine function of h PB-EPCs. Stem Cells 2014;32:2679–2689