(193c) pH-Dependent PDGF-BB-Induced Chemokinesis and Chemotaxis of NIH 3T3 Fibroblasts and Rat Bone Marrow-Derived Mesenchymal Stem Cells

Cell migration plays an essential feature in many physiological and pathological processes as well as in wound healing and scaffold-based tissue engineering. In the microenvironment experienced by the pH of the cell is a key factor that influences their behavior, such as motility. For example, in wound healing, a low pH is known to be beneficial, while a high pH is disadvantageous. However, surprisingly few studies are available on the effect of pH on cell migration, and its influence on cellular directional decision-making processes. Moreover, there is no consensus on how pH affects the chemokinesis and chemotaxis of different cell lines, or whether it can be used to control cell migration. We hypothesize that the modulating the pH can lead to increases or decreases in cell speed, as well as can provide the ability to control cell directional decisions. Therefore, we aim to examine the effect of pH on the migration of mouse embryo fibroblast cells (NIH 3T3) and mesenchymal stem cells (MSCs) - two important cell types for tissue engineering. To that end, fibroblasts and MSCs were exposed to different pH levels ranging from 4.0 to 12.0, either in the presence or absence of a chemotactic factor (i.e. Platelet-derived growth factor – BB); and their migration was tracked over time using an automated Olympus microscope. Migration speed, directionality, directional persistence, morphology, and viability of the cells were quantitatively determined and descriptive statistics are reported. It was found that the motility of both cell types were inhibited at acidic and alkaline conditions even in the presence of 25 ng/ml of PDGF-BB. Cells’ migration was completely restricted at pH 4.5 even though their viability was not affected, as confirmed by a viability assay. The fibroblast and mesenchymal stem cells migration was greatest at pH 7.4. The presented approach is expected to yield an enhanced fundamental understanding of cell migration for both cells lines NIH 3T3 and MSCs. Moreover, it was found that the change in pH conditions can be used to control the various modes of cell motility. Our results highlight a prominent role of pH in chemotaxis and provide potential tools for controlling tissue development, wound healing in scaffold-based tissue engineering. For example, pH could be used to obtained a desired cell speed and/or induce a specific type to migrate into a scaffold (while excluding other cell types). Furthermore, the data provided by our study can be beneficial to further understanding the mechanism of cancer metastasis, where pH can also be a significant factor.