VEGF treatment promotes bone marrow-derived CXCR4+ mesenchymal stromal stem cell differentiation into vessel endothelial cells

Abstract

Stem/progenitor cells serve an important role in the process of blood vessel repair. However, the mechanism of vascular repair mediated by C-X-C chemokine receptor type 4-positive (CXCR4+) bone marrow-derived mesenchymal stem cells (BMSCs) following myocardial infarction remains unclear. The aim of the present study was to investigate the effects of vascular endothelial growth factor (VEGF) on vessel endothelial differentiation from BMSCs. CXCR4+ BMSCs were isolated from the femoral bone marrow of 2-month-old mice and the cells were treated with VEGF. Expression of endothelial cell markers and the functional properties were assessed by reverse transcription-quantitative polymerase chain reaction, flow cytometry and vascular formation analyses. The results indicated that the CXCR4+ BMSCs from femoral bone marrow cells expressed putative cell surface markers of mesenchymal stem cells. Treatment with VEGF induced platelet/endothelial cell adhesion molecule-1 (PECAM-1) and von Willebrand factor (vWF) expression at the transcriptional and translational levels, compared with untreated controls. Moreover, VEGF treatment induced CXCR4+ BMSCs to form hollow tube-like structures on Matrigel, suggesting that the differentiated endothelial cells had the functional properties of blood vessels. The results demonstrate that the CXCR4+ BMSCs were able to differentiate into vessel endothelial cells following VEGF treatment. For cell transplantation in vascular disease, it may be concluded that CXCR4+ BMSCs are a novel source of endothelial progenitor cells with high potential for application in vascular repair.

Transplantation of Bone Marrow Mesenchymal Stem Cells Prevents Radiation‐Induced Artery Injury by Suppressing Oxidative Stress and Inflammation

“…More and more evidences show that BMSCs could directly differentiate into vascular endothelial cells and smooth muscle cells, even forming functional vessels [ 15 , 60 ]. However, reports suggest that differentiation either by transdifferentiation or cell fusion appears too low to explain the significant improvement of vascular repair [ 61 ].…”

“…MSCs orchestrate the repair process of injured vessels by various mechanisms such as transdifferentiation, microvesicles or exosomes, and secreting cytokines [ 13 , 14 ]. MSCs can directly differentiate into endothelial cells to participate in angiogenesis [ 15 ] or migrate and home to the injured large blood vessel for vascular repair by regulating various cell cytokines, such as transforming growth factor beta (TGF- β ), vascular endothelial growth factor (VEGF), and intercellular cell adhesion molecules (ICAM) [ 16 , 17 ].…”

To Explore the Pathogenesis of Vascular Lesion of Type 2 Diabetes Mellitus Based on the PI3K/Akt Signaling Pathway

“…Numerous studies have demonstrated that obesity, insulin resistance, and type 2 diabetes are associated with abnormal endothelial function and participate in the occurrence and development of diabetes mellitus and small vascular complications [8]. Vascular endothelial growth factor (VEGF) is a crucial cytokine used to promote the formation of new blood vessels, which may promote vascular endothelial cells, smooth muscle cell mitosis, vascular permeability, and angiogenesis [9, 10]. Previous studies on the association between VEGF and vascular disease revealed that serum VEGF was significantly increased in patients with diabetes mellitus, and the increase of VEGF was closely associated with the germination of diabetic angiopathy [11, 12].…”

A brief review: the therapeutic potential of bone marrow mesenchymal stem cells in myocardial infarction

“…Combination therapy significantly increased vascular density, decreased the formation of scar tissue, and improved cardiac function compared to either treatment alone or to untreated infarcted control rats [ 40 ]. VEGF treatment also promoted the differentiation of CXCR4-positive BMSCs into vessel endothelial cells in vitro [ 41 ]. Another research study has suggested that overexpression of the cellular repressor of adenovirus E1A-stimulated genes in BMSCs may promote VEGF-induced angiogenesis by inhibiting Von Hippel-Lindau tumor suppressor-mediated HIF-1α degradation, consequently protecting against rat MI [ 42 ].…”