TY  - GEN
TI  - Characterization of cell-matrix interactions during multipotent mesenchymal stromal cell (MSC) differentiation
AV  - public
A1  - Angstmann, Michael
KW  - mesenchymale Stammzellen 
KW  -  multipotene mesenchymale Stromazellen 
KW  -  Impedanz 
KW  -  extrazelluläre Matrix 
KW  -  Differenzierungmesenchymal stromal cells 
KW  -  mesenchymal stem cells 
KW  -  impedance 
KW  -  extracellular matrix 
KW  -  differentiation
N2  - For their huge variety of functions mesenchymal stromal/stem cells (MSCs) are attractive candidates for tissue engineering and cell therapy. Although in vitro differentiation of MSCs is well established and has been extensively studied, little is known about stem cell niches. So how are these niches defined in tissues and which cell-matrix contacts determine the fate of MSCs therein? To approach this task, herein the adhesive behavior of MSCs was evaluated under varying conditions employing non-invasive impedance monitoring in real-time, using fibroblast and keratinocytes as non-specific controls. Major focus was on changes in adhesion and migration of MSCs induced to differentiate into adipogenic and osteogenic lineages, the effects of extracellular matrix (ECM) contacts on this response, and the correlation of impedance profiles with specific differentiation markers including the predictive value of these recorded profiles. Finally, the influence of the MSC source was evaluated by comparing different cell populations derived from bone marrow and fat tissue. MSCs roughly resembled fibroblast adhesion while keratinocytes differed significantly, which was reflected by impedance recordings. Inducing differentiation, impedance profiles of MSCs driven into the osteogenic lineage revealed a continuous rise of impedance due to matrix deposition and strong cell-matrix contacts and furthermore by maturation and formation of a mineralized matrix. Adipogenic differentiation was marked by shallower initial slopes and eventually declining profiles, corresponding to more compact and roundish cells with lowered cell-cell contacts. Concordance of impedance profiles and differentiation markers of the varying differentiation potential of MSCs from different donor and age underlined the reliability of the system. MSC migration was delayed during adipogenesis or by increasing cell attachment in response to TNF alpha treatment. Pre-coating with ECM proteins revealed favored osteogenesis on collagen I and IV, whereas adipogenesis was increased on fibronectin, which was also reflected by impedance recordings. Overall, the present thesis revealed distinct differences of cell attachment during the process of differentiation and the guidance of differentiation by cell-matrix contacts and evaluated the potential of impedance measurements as a valuable tool for real-time, non-invasive high throughput screening of cell properties and identification of receptors involved in the regulation of differentiation processes.
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/12558/
ID  - heidok12558
Y1  - 2011///
ER  -