(14b) Soluble GROWTH FACTORS Mediate Mesenchymal STEM CELL Migration to TUMORS

Mesenchymal stem cells (MSCs) have emerged as a potential candidate for the development of cell-based therapeutics and engineered tissues. In recent years, human and animal MSCs have been derived from different sources, including bone marrow, placenta, and umbilical cord blood. Bone marrow-derived MSCs are an extensively characterized, highly proliferative, multi-potent population, which migrate spontaneously to different organs for tissue regeneration¹. In vivo, MSCs have been shown to migrate and accumulate in tumor tissues. Several studies have demonstrated their immunosuppressive characteristics, which makes them an attractive source for the development of allogeneic cell-based cancer therapeutics. However, ex vivo culture, expansion and manipulation affects the mobility of MSCs limiting their migration after reinfusion and drastically reducing their accumulation in tumors. In vivo, tumor secreted soluble factors, including transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and platelet derived growth factor (PDGF), mobilize bone marrow-derived MSCs into the circulation². We hypothesized that TGF- β1, VEGF, and PDGF mobilize MSCs into the circulation by altering their mechanical properties³. We systematically characterized the microscopic mechanical properties of MSCs, including their cytoskeletal rheology, cell adhesion molecule expression, cell elongation, and migratory behavior. In vitro migration studies were used to determine the concentrations of soluble growth factors to be used in mechanical characterization. At the concentrations selected all three growth factors increased MSC migration; however, only TGF-β1 altered microscopic mechanical properties, including cytoskeletal rheology and cell adhesion molecule expression.

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3. Ponte, A. L., Marais, E. et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells 25, 1737-1745, (2007).