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Mesenchymal stem cells and neovascularization: role of platelet-derived growth factor receptors.

Ball SG, Shuttleworth CA, Kielty CM - J. Cell. Mol. Med. (2007 Sep-Oct)

Bottom Line: There is now accumulating evidence that bone marrow-derived mesenchymal stem cells (MSCs) make an important contribution to postnatal vasculogenesis, especially during tissue ischaemia and tumour vascularization.Despite the fact that MSCs did not express VEGF receptors, we have recently identified that VEGF-A can stimulate platelet-derived growth factor (PDGF) receptors, which regulates MSC migration and proliferation.This review focuses on the role of PDGF receptors in regulating the vascular cell fate of MSCs, with emphasis on the function of the novel VEGF-A/PDGF receptor signalling mechanism.

View Article: PubMed Central - PubMed

Affiliation: UK Centre for Tissue Engineering, Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester, Manchester, UK.

ABSTRACT
There is now accumulating evidence that bone marrow-derived mesenchymal stem cells (MSCs) make an important contribution to postnatal vasculogenesis, especially during tissue ischaemia and tumour vascularization. Identifying mechanisms which regulate the role of MSCs in vasculogenesis is a key therapeutic objective, since while increased neovascularization can be advantageous during tissue ischaemia, it is deleterious during tumourigenesis. The potent angiogenic stimulant vascular endothelial growth factor (VEGF) is known to regulate MSC mobilization and recruitment to sites of neovascularization, as well as directing the differentiation of MSCs to a vascular cell fate. Despite the fact that MSCs did not express VEGF receptors, we have recently identified that VEGF-A can stimulate platelet-derived growth factor (PDGF) receptors, which regulates MSC migration and proliferation. This review focuses on the role of PDGF receptors in regulating the vascular cell fate of MSCs, with emphasis on the function of the novel VEGF-A/PDGF receptor signalling mechanism.

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Schematic diagrams highlighting potential mechanisms regulating PDGF receptor signalling.(A) MSC autocrine VEGF-A expression may regulate paracrine PDGF ligand stimulation of PDGF receptors, by VEGF-A competitively binding to PDGF receptors and competing with PDGF concentration gradients. (B) Modulation of VEGF-A induced PDGF receptor signalling specificity is likely to be multifactorial, depending in part on quantitative and qualitative differences, such as; (1) local oxygen concentration regulating VEGF-A expression, (2) matrix sequestration and retention of VEGF-A, (3) soluble VEGF-A level, (4) concentration of PDGF ligands, (5) integrin-matrix interactions, (6) local membrane-associated proteins, (7) recruitment of signalling molecules.
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fig01: Schematic diagrams highlighting potential mechanisms regulating PDGF receptor signalling.(A) MSC autocrine VEGF-A expression may regulate paracrine PDGF ligand stimulation of PDGF receptors, by VEGF-A competitively binding to PDGF receptors and competing with PDGF concentration gradients. (B) Modulation of VEGF-A induced PDGF receptor signalling specificity is likely to be multifactorial, depending in part on quantitative and qualitative differences, such as; (1) local oxygen concentration regulating VEGF-A expression, (2) matrix sequestration and retention of VEGF-A, (3) soluble VEGF-A level, (4) concentration of PDGF ligands, (5) integrin-matrix interactions, (6) local membrane-associated proteins, (7) recruitment of signalling molecules.

Mentions: Besides VEGF-A165 being able to induce MSC migration, we also demonstrated that when VEGF-A165 was localized at the cell surface, it could inhibit PDGF-induced MSC migration, presumably by competing for PDGF receptor occupancy [9]. Since MSCs can express and secrete high levels of VEGF-A, especially in atmospheres of reduced oxygen, this suggests an intriguing possibility that autocrine VEGF-A production could regulate paracrine PDGF responses. A schematic diagram representing this proposed mechanism is shown in Figure 1A.


Mesenchymal stem cells and neovascularization: role of platelet-derived growth factor receptors.

Ball SG, Shuttleworth CA, Kielty CM - J. Cell. Mol. Med. (2007 Sep-Oct)

Schematic diagrams highlighting potential mechanisms regulating PDGF receptor signalling.(A) MSC autocrine VEGF-A expression may regulate paracrine PDGF ligand stimulation of PDGF receptors, by VEGF-A competitively binding to PDGF receptors and competing with PDGF concentration gradients. (B) Modulation of VEGF-A induced PDGF receptor signalling specificity is likely to be multifactorial, depending in part on quantitative and qualitative differences, such as; (1) local oxygen concentration regulating VEGF-A expression, (2) matrix sequestration and retention of VEGF-A, (3) soluble VEGF-A level, (4) concentration of PDGF ligands, (5) integrin-matrix interactions, (6) local membrane-associated proteins, (7) recruitment of signalling molecules.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401270&req=5

fig01: Schematic diagrams highlighting potential mechanisms regulating PDGF receptor signalling.(A) MSC autocrine VEGF-A expression may regulate paracrine PDGF ligand stimulation of PDGF receptors, by VEGF-A competitively binding to PDGF receptors and competing with PDGF concentration gradients. (B) Modulation of VEGF-A induced PDGF receptor signalling specificity is likely to be multifactorial, depending in part on quantitative and qualitative differences, such as; (1) local oxygen concentration regulating VEGF-A expression, (2) matrix sequestration and retention of VEGF-A, (3) soluble VEGF-A level, (4) concentration of PDGF ligands, (5) integrin-matrix interactions, (6) local membrane-associated proteins, (7) recruitment of signalling molecules.
Mentions: Besides VEGF-A165 being able to induce MSC migration, we also demonstrated that when VEGF-A165 was localized at the cell surface, it could inhibit PDGF-induced MSC migration, presumably by competing for PDGF receptor occupancy [9]. Since MSCs can express and secrete high levels of VEGF-A, especially in atmospheres of reduced oxygen, this suggests an intriguing possibility that autocrine VEGF-A production could regulate paracrine PDGF responses. A schematic diagram representing this proposed mechanism is shown in Figure 1A.

Bottom Line: There is now accumulating evidence that bone marrow-derived mesenchymal stem cells (MSCs) make an important contribution to postnatal vasculogenesis, especially during tissue ischaemia and tumour vascularization.Despite the fact that MSCs did not express VEGF receptors, we have recently identified that VEGF-A can stimulate platelet-derived growth factor (PDGF) receptors, which regulates MSC migration and proliferation.This review focuses on the role of PDGF receptors in regulating the vascular cell fate of MSCs, with emphasis on the function of the novel VEGF-A/PDGF receptor signalling mechanism.

View Article: PubMed Central - PubMed

Affiliation: UK Centre for Tissue Engineering, Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester, Manchester, UK.

ABSTRACT
There is now accumulating evidence that bone marrow-derived mesenchymal stem cells (MSCs) make an important contribution to postnatal vasculogenesis, especially during tissue ischaemia and tumour vascularization. Identifying mechanisms which regulate the role of MSCs in vasculogenesis is a key therapeutic objective, since while increased neovascularization can be advantageous during tissue ischaemia, it is deleterious during tumourigenesis. The potent angiogenic stimulant vascular endothelial growth factor (VEGF) is known to regulate MSC mobilization and recruitment to sites of neovascularization, as well as directing the differentiation of MSCs to a vascular cell fate. Despite the fact that MSCs did not express VEGF receptors, we have recently identified that VEGF-A can stimulate platelet-derived growth factor (PDGF) receptors, which regulates MSC migration and proliferation. This review focuses on the role of PDGF receptors in regulating the vascular cell fate of MSCs, with emphasis on the function of the novel VEGF-A/PDGF receptor signalling mechanism.

Show MeSH
Related in: MedlinePlus