Mesenchymal stem cells promote endothelial progenitor cell migration, vascularization, and bone repair in tissue‐engineered constructs via activating CXCR2‐Src‐PKL/Vav2‐Rac1

2018 ◽  
Vol 32 (4) ◽  
pp. 2197-2211 ◽  
Author(s):  
Zhilin Li ◽  
Aijun Yang ◽  
Xiaolong Yin ◽  
Shiwu Dong ◽  
Fei Luo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Migration ◽  
Endothelial Progenitor Cell ◽  
Progenitor Cell ◽  
Bone Repair ◽  
Endothelial Progenitor

scholarly journals TNFα regulates endothelial progenitor cell migration through the NF‐κB pathway (1180.16)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Anthony Prisco ◽  
Brian Hoffmann ◽  
Catherine Kaczorowski ◽  
Andrew Greene
Keyword(s):  
Cell Migration ◽  
Endothelial Progenitor Cell ◽  
Progenitor Cell ◽  
Endothelial Progenitor

scholarly journals CircRNA-vgll3 promotes osteogenic differentiation of adipose-derived mesenchymal stem cells via modulating miRNA-dependent integrin α5 expression

2020 ◽  
Vol 28 (1) ◽  
pp. 283-302
Author(s):  
Dandan Zhang ◽  
Ni Ni ◽  
Yuyao Wang ◽  
Zhimin Tang ◽  
Huiqin Gao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Osteogenic Differentiation ◽  
Progenitor Cell ◽  
Bone Repair ◽  
Circular Rnas ◽  
Mineral Density ◽  
Differentiation Potential ◽  
Integrin Α5

AbstractAdipose-derived mesenchymal stem cells (ADSCs) are promising candidate for regenerative medicine to repair non-healing bone defects due to their high and easy availability. However, the limited osteogenic differentiation potential greatly hinders the clinical application of ADSCs in bone repair. Accumulating evidences demonstrate that circular RNAs (circRNAs) are involved in stem/progenitor cell fate determination, but their specific role in stem/progenitor cell osteogenesis, remains mostly undescribed. Here, we show that circRNA-vgll3 originating from the vgll3 locus markedly enhances osteogenic differentiation of ADSCs; nevertheless, silencing of circRNA-vgll3 dramatically attenuates ADSC osteogenesis. Furthermore, we validate that circRNA-vgll3 functions in ADSC osteogenesis through a circRNA-vgll3/miR-326-5p/integrin α5 (Itga5) pathway. Itga5 promotes ADSC osteogenic differentiation and miR-326-5p suppresses Itga5 translation. CircRNA-vgll3 directly sequesters miR-326-5p in the cytoplasm and inhibits its activity to promote osteogenic differentiation. Moreover, the therapeutic potential of circRNA-vgll3-modified ADSCs with calcium phosphate cement (CPC) scaffolds was systematically evaluated in a critical-sized defect model in rats. Our results demonstrate that circRNA-vgll3 markedly enhances new bone formation with upregulated bone mineral density, bone volume/tissue volume, trabeculae number, and increased new bone generation. This study reveals the important role of circRNA-vgll3 during new bone biogenesis. Thus, circRNA-vgll3 engineered ADSCs may be effective potential therapeutic targets for bone regenerative medicine.

Abstract 16812: ETV2- Rhoj Cascade Regulates Endothelial Progenitor Cell Migration During Embryogenesis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Javier Sierra-Pagan ◽  
BHAIRAB N SINGH ◽  
Wuming Gong ◽  
Satyabrata Das ◽  
Erik Skie ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endothelial Progenitor Cell ◽  
Progenitor Cell ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Embryoid Bodies ◽  
Endothelial Progenitor ◽  
Vascular Plexus ◽  
Upstream Regulator ◽  
Endothelial Progenitors

Background: Endothelial progenitors migrate early during embryogenesis to form the primary vascular plexus. ETV2, an Ets-transcription factor, governs the specification of the earliest hemato-endothelial progenitors during embryogenesis. The regulatory mechanisms that govern their migration are undefined. In the present study, we describe a novel role for ETV2 in cell migration and provide evidence for an ETV2 -Rhoj network as a mechanism responsible for this process. Approach and Results: We analyzed our RNAseq datasets, which revealed robust enrichment of migratory/motility pathways following overexpression of ETV2 during mesodermal differentiation. We then analyzed ETV2 ChIPseq and ATACseq datasets, which showed enrichment of ChIPseq peaks with increased chromatin accessibility in migratory genes following overexpression of ETV2. Additionally, scratch and sprouting assays showed that overexpression of ETV2 enhanced cell migration in mouse embryonic stem cells (ESCs), embryoid bodies (EBs) and mouse embryonic fibroblasts (MEFs). Knockout of Etv2 led to migratory defects of Etv2-EYFP + angioblasts to their pre-defined regions of developing embryos relative to wildtype controls at embryonic day (E) 8.5, supporting its role during migration. Mechanistically, we showed that ETV2 binds to the promoter region of Rhoj serving as an upstream regulator of cell migration. Single cell RNAseq analysis of Etv2-EYFP + sorted cells revealed co-expression of Etv2 and Rhoj in endothelial progenitors at E7.75 and E8.25. Overexpression of ETV2 led to a robust increase in Rhoj in both EBs and MEFs, whereas, its expression was abolished in the Etv2 knockout EBs. Finally, shRNA-mediated knockdown of Rhoj resulted in migratory defects which were rescued by overexpression of ETV2. Conclusions: These results define an ETV2 -Rhoj cascade, which is important for the regulation of endothelial progenitor cell migration during embryogenesis.

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