EN
Cell adhesion to extracellular matrix (ECM) generates intracellular signals that modulate cell survival, proliferation, migration of neural precursor cells and differentiation in vitro. The function of ECM in developmental processes may be associated with particular patterns of proteolysis of ECM. Among the proteases the matrix metalloproteinases (MMPs) represent family of enzymes responsible for the modification of ECM components and by this may influence cell development. The aim of our study was to determine the potential of native ECM proteins: fibronectin, laminin and collagen, on the proliferation and differentiation of HUCB-NSCs cultured in serum free condition. In an effort to elucidate the engagement of MMPs we have checked the effect of inhibitors - SB-3CT, GM6001 and doxycycline on the above development-associated processes. Among the tested substrates the highest proliferation rate (evaluated by using anti-Ki67) was noted in the presence of fibronectin. Fibronectin also occurred most permissive substrate in HUCB-NSCs differentiation toward neuronal fate. The endogenous activity of MMPs (assayed by in situ zymography) corresponds to the rate of cell proliferation. Addition of MMPs inhibitors resulted in the significant suppression of proliferation potential and inhibition of neuronal cell generation (TUJ1- and MAP2-positive) with simultaneous promotion of oligo- and astroglial cells (expressing GALC and S100β, respectively). In conclusion, our results suggest that MMPs might be an important component in neurogenesis-associated processes. Supported by MSRHE grants: 0154/B/ P01/2010/38 and 0345/B/P01/2010/38.