Basic Fibroblast Growth Factor Controls Migration in Human Mesenchymal Stem Cells

Abstract

Little is known about the migration of mesenchymal stem cells (MSCs). Some therapeutic approaches had demonstrated that MSCs were able to regenerate injured tissues when applied from different sites of application. This implies that MSCs are not only able to migrate but also that the direction of migration is controlled. Factors that are involved in the control of the migration of MSCs are widely unknown. The migratory ability of isolated MSCs was tested in different conditions. The migratory capability was examined using Boyden chamber assay in the presence or absence of basic fibroblast growth factor (bFGF), erythropoietin, interleukin-6, stromal cell-derived factor-␤, and vascular endothelial growth factor. bFGF in particular was able to increase the migratory activity of MSCs through activation of the Akt/protein kinase B (PKB) pathway. The results were supported by analyzing the orientation of the cytoskeleton. In the presence of a bFGF gradient, the actin filaments developed a parallelized pattern that was strongly related to the gradient. Surprisingly, the influence of bFGF was not only an attraction but also routing of MSCs. The bFGF gradient experiment showed that low concentrations of bFGF lead to an attraction of the cells, whereas higher concentrations resulted in repulsion. This ambivalent effect of bFGF provides the possibility to a purposeful routing of MSCs.

Periodontal regeneration following application of basic fibroblast growth factor-2 in combination with beta tricalcium phosphate in class III furcation defects in dogs

“…We attempted to determine the optimal dose of bFGF-2 for periodontal regeneration in dogs from several previous reports. bFGF-2 had a dose-dependent effect on periodontal regeneration at a dose ranging from 0 to 0.16% per implant [3][4][5][6][7][8][9][10][11][12][13][14][15][26][27][28][29] . Hayashi et al reported that new bone formation was smaller in the 0.56% bFGF-2 (100 µg bFGF-2/3×3×2 mm gelatin hydrogel) implant compared to the 0.056% bFGF-2 (10 µg bFGF-2/3×3×2 mm gelatin hydrogel) implant; however, there were no significant differences between them 29) .…”

“…Basic fibroblast growth factor-2 (bFGF-2) is a heparinbinding growth factor that exhibits potent angiogenic activity and mitogenic ability in mesenchymal cells [1][2][3][4][5][6][7] and periodontal ligament cells [8][9][10][11] . Several studies have reported that bFGF-2 induces potent periodontal tissue regeneration along with new alveolar bone and cementum formation without aberrant healing such as root resorption and ankylosis in critical size defects of animal models [12][13][14] .…”

Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells

“…MSC demonstrate an increased migratory propensity in the presence of basic fibroblast growth factor through a phosphoinositide-3 kinase/AKT pathway downstream of the basic fibroblast growth factor receptor on the MSC. 51 Chemokine/cytokine secretion and the respective receptors found on MSC Monocyte-chemoattractant protein 1 (CCL2), a chemokine secreted by tumor cells, was shown to be a potent chemoattractant for MSC migration toward breast carcinomas. 52 However, prior studies show conflicting data on the migratory response to CCL2.…”

Composite Growth Factor Supplementation Strategies to Enhance Tenocyte Bioactivity in Aligned Collagen-GAG Scaffolds

“…Along with PDGF-BB and IGF-1, we investigated three additional factors: the basic fibroblast growth factor (bFGF), the stromal cell-derived factor 1a (SDF-1a), and the growth/differentiation factor 5 (GDF-5). The growth factor bFGF has shown the capacity to improve tenocyte proliferation and collagen synthesis, 22 MSC chemotaxis, 31 and the tenogenic differentiation of MSCs both in two-dimensional (2D) 32 and 3D 33 culture systems. SDF-1a has been implicated as a potent chemoattractant of MSCs during wound healing, 29,34 but recently has shown the ability to improve ligament stem cell proliferation and migration 35 as well as functional tendon regeneration in a rat Achilles model.…”