Thesis supervisor: UT Senior Associate Professor Sulev Ingerpuu, UT professor Toivo Maimets ja UT Senior Research Fellow Viljar Jaks
Opponent: Professor dr. Gerd Klein, University of Tübingen
All animal cells interact with extracellular matrix (ECM) either continuously or during important phases of their life-time. ECM provides mechanical support for tissues and is thus necessary for building up organs with complex structures. The interactions between cells and ECM regulate cell growth, migration and differentiation. The major components of ECM are proteins and polysaccharides that are secreted by various cell types. Collagens and laminins are examples of widely-studied ECM proteins.
The research presented in the current thesis was designed to study the ways in which cells interact with the surrounding extracellular matrix and how these bidirectional interactions affect cell growth and differentiation. Firstly, we studied how topographical properties of silica-based surfaces affect the growth of human dermal fibroblasts. Surfaces with four different sizes of round structural elements were produced (200 nm, 500nm, 1 µm ja 10 µm). It was found that increase in the size of these structural elements coincided with the decrease in cell growth and induced cell senescence. The second study demonstrated that electrospun gelatin-based scaffolds that contain glucose are suitable for growth of primary dermal fibroblasts. These scaffolds induced expression of ECM proteins such as laminins in fibroblasts. The third study investigated the localization and secretion of laminins in human platelets. Our investigation revealed that platelets do not store laminins in typical alpha granules as was shown previously, and that these proteins are secreted via microvesicles but not via exosomes when platelets become activated. The fourth study of this thesis characterized the expression of laminins in human embryonic stem cells. We observed that the relative amount of laminin-511 increases while the amount of laminin-521 decreases during early differentiation induced by retinoic acid. Additionally, we found that human embryonic stem cells express a wider range of different laminin chains than previously described, and that the laminin repertoire was independent of their differentiation status.