Effect of human endothelial cells on Human Bone Marrow Stromal Cell phenotype: Role of VEGF?

Abstract

Angiogenesis is a tightly regulated process involved in growth, repair, and bone remodeling. Several studies have shown that there is a reciprocal regulation and functional relationship between endothelial cells and osteoblast-like cells during osteogenesis, where systemic hormones and paracrine growth factors play an active role. Angiogenesis is induced by a variety of growth factors; among them vascular endothelial growth factor (VEGF) may be an important mediator for the angiogenic process involved in bone physiology. We studied the VEGF effect on osteoblast progenitor cells (Human Bone Marrow Stromal Cells: HBMSE) cultured alone or associated with endothelial cells (Human Umbilical Vein Endothelial Cells: HUVEC) in different co-culture models (co-culture with or without direct contact, conditioned medium), to determine the influence of VEGF on these cells and on their relationship. In agreement with other studies, we show that HBMSC express and synthesize VEGF, HUVEC conditioned medium has a proliferative effect on them, and early osteoblastic marker (Alkaline phosphatase activity) levels increase when these cells are co-cultured with HUVEC only in direct contact. However, unlike previous studies, we did not find that VEGF increased these processes. These results suggest that the intercommunication between endothelial cells and osteoblastic-like cells requires not only diffusible factors, but also involving cell membrane proteins.

Recruitment of mesenchymal stem cells and expression of TGF‐β1 and VEGF in the early stage of shock wave‐promoted bone regeneration of segmental defect in rats

“…VEGF-A expression in maturation stages of osteochondral cells was significantly increased 28 days after ESW treatment. These findings support previous studies that VEGF is responsible for hypertrophied cartilage neovascularization [4,38]. In our study, intensive TGF-P1 and VEGF-A expression in defect tissue suggests that their production is directly or indirectly promoted by physical stimulation provided by ESW treatment, and that TGF-P1 and VEGF are actively involved in recruitment and differentiation of mesenchymal stem cells.…”

Mannitol enhances delivery of marrow stromal cells to the brain after experimental intracerebral hemorrhage

“…Cell therapy induces neurorestorative changes in the brain reflective of several mechanisms of action; however, the ability of MSCs to localize to a region of brain injury and increase local concentrations of growth factors such as BDNF and VEGF may be paramount (Villars et al, 2000. Various cell concentrations and routes of administration have been applied to demonstrate the therapeutic efficacy of MSC treatment of neural injury .…”

“…MSCs have shown the capacity to differentiate into neurons and astrocytes and have the ability to preferentially migrate to damaged cortex (Kopen et al, 1999). Of particular significance is the ability of MSCs to secrete or stimulate secretion of growth factors which create a local environment conducive for neuroregeneration (Villars et al, 2000).…”

Coculture of Spheroids/2D Cell Layers Using a Miniaturized Patterned Platform as a Versatile Method to Produce Scaffold‐Free Tissue Engineering Building Blocks

“…Both are known to drive an increased expression of this marker in early time points. [30][31][32][33][34][35] Double stranded DNA (dsDNA) quantification showed that the stem cell spheroids produced in different coculture procedures presented approximately three times more dsDNA than the control conditions (cultured as monocultures in either α-MEM or M199) ( Figure 1c). Similar results were previously reported for other indirect coculture methods, where stem cell proliferation was increased via coculture with osteoblast cells [30,31] and HUVEC cells.…”