Article

The ratio of VEGF/PEDF expression in bone marrow mesenchymal stem cells regulates neovascularization.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove Campus, Brisbane Qld 4059, Australia.
Differentiation (Impact Factor: 2.84). 03/2011; 81(3):181-91. DOI: 10.1016/j.diff.2010.12.003
Source: PubMed

ABSTRACT Angiogenesis, or neovascularization, is a finely balanced process controlled by pro- and anti-angiogenic factors. Vascular endothelial growth factor (VEGF) is a major pro-angiogenic factor, whereas pigment epithelial-derived factor (PEDF) is the most potent natural angiogenesis inhibitor. In this study, the regulatory role of bone marrow stromal cells (BMSCs) during angiogenesis was assessed by the endothelial differentiation potential, VEGF/PEDF production and responses to pro-angiogenic and hypoxic conditions. The in vivo regulation of blood vessel formation by BMSCs was also explored in a SCID mouse model. Results showed that PEDF was expressed more prominently in BMSCs compared to VEGF. This contrasted with human umbilical vein endothelial cells (HUVECs) where the expression of VEGF was higher than that of PEDF. The ratio of VEGF/PEDF gene expression in BMSCs increased when VEGF concentration reached 40ng/ml in the culture medium, but decreased at 80ng/ml. Under CoCl(2)-induced hypoxic conditions, the VEGF/PEDF ratio of BMSCs increased significantly in both normal and angiogenic culture media. There was no expression of endothelial cell markers in BMSCs cultured in either pro-angiogenic or hypoxia culture conditions when compared with HUVECs. The in vivo study showed that VEGF/PEDF expression closely correlated with the degree of neovascularization, and that hypoxia significantly induced pro-angiogenic activity in BMSCs. These results indicate that, rather than being progenitors of endothelial cells, BMSCs play an important role in regulating the neovascularization process, and that the ratio of VEGF and PEDF may, in effect, be an indicator of the pro- or anti-angiogenic activities of BMSCs.

0 Followers
 · 
190 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this in vitro study was to determine the effect of zoledronate, which is frequently used to treat osteoporosis, on osteoarthritis by analyzing zoledronate-induced expression of vascular endothelial growth factor-A (VEGF-A) in chondrocytes and synovial cells. After chondrocytes and synovial cells were separated and cultured, zoledronate was added, and VEGF-A and pigment epithelium-derived factor (PEDF) expression were quantified by real-time polymerase chain reaction and Western blotting. There was no significant difference in the expression of VEGF-A mRNA in chondrocytes between the zoledronate group and the control group on the 8th day of culture. The expression of both VEGF-A and PEDF mRNA in synovial cells was significantly decreased in the zoledronate group (P<0.05). Zoledronate decreases the expression of VEGF-A in synovial cells and may affect the development and progression of osteoarthritis.
    11/2014; 21(4):249-255. DOI:10.11005/jbm.2014.21.4.249
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Transplantation of bone marrow stromal cells (BMSCs) or Schwann cells (SCs) can increase axonal regeneration in peripheral nerve injuries. Based on our previous investigations, the goal of the present work was to examine the individual and synergistic effects of the two different cell types in sciatic nerve injury. We pursued to evaluate the effects of BMSCs and SCs co-transplantation on the functional recovery after sciatic nerve injury in rat. Methods In this experimental research, adult male Wistar rats (n = 32, 250-300g) were used, BMSCs and SCs were cultured, and the SCs were confirmed with anti S100 antibody. Rats were randomly divided into 4 groups (n = 8 in each group): 1-control group: silicon tube filled with fibrin gel without cells; 2-BMSCs group: silicon tube filled with fibrin gel seeded with BMSCs; 3-SCs group: silicon tube filled with fibrin gel seeded with SCs and 4-co-transplantation group: silicone tube filled with fibrin gel seeded with BMSCs and SCs. The left sciatic nerve was exposed, a 10 mm segment removed, and a silicone tube interposed into this nerve gap. BMSCs and SCs were transplanted separately or in combination into the gap. BMSCs were labeled with anti-BrdU and SCs were labeled with DiI. After 12 weeks electromyographic and functional assessments were performed and analyzed by one-way analysis of variance (ANOVA). Results Electromyographic and functional assessments showed a significant difference between the experimental groups and controls. Electromyography measures were significantly more favourable in SCs transplantation group as compared to BMSCs transplantation and co-transplantation groups (p < 0.05). Functional assessments showed no statistically significant difference among the BMSCs, SCs and co-transplantation groups (p < 0.05). Discussion Transplantation of BMSCs and SCs separately or in combination have the potential to generate functional recovery after sciatic nerve injury in rat. The electromyography evaluation showed a greater improvement after SCs transplantation than BMSCs or the co-transplantation of BMSCs and SCs.
    Autonomic neuroscience: basic & clinical 05/2013; 4(4):291-8. · 1.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human Mesenchymal Stromal/Stem Cells (MSCs) are adult multipotent cells that behave in a highly plastic manner, inhabiting the stroma of several tissues. The potential utility of MSCs is nowadays strongly investigated in the field of regenerative medicine and cell therapy, although many questions about their molecular identity remain uncertain.
    BMC Genomics 10/2014; 15(1):910. DOI:10.1186/1471-2164-15-910 · 4.04 Impact Factor

Full-text (5 Sources)

Download
41 Downloads
Available from
May 28, 2014