Skirtingų suaugusio žmogaus audinių mezenchiminių kamieninių ląstelių funkcionavimo mechanizmų tyrimai

Abstract

Human mesenchymal stem cells (MSC) have attracted a great deal of interest for their potential use in regenerative medicine and suppression of the inflammation. Nevertheless, all known therapy protocols require large amounts of MSCs, which can be obtained only by in vitro expansion. One of the most important methodological problems is associated with the use of animal-derived components in the cell culture medium. The main aim of the current research was to elucidate the influence of different serum substitutes on the proliferation, differentiation, expression of cell surface markers, and total protein expression of mesenchymal stem cells derived from human adipose tissue. In addition we were aiming to determine the features of mesenchymal stem cell populations from an exfoliated deciduous tooth (SHED) and their response to the multifunctional proinflammatory protein alpha1-antitrypsin. Our results indicate that adipose tissue derived MSCs cultivated in the presence of fetal calf serum and allogeneic human serum display similar properties, while synthetic serum substitute induces increase in growth and differentiation potential of MSCs. Moreover, our results indicate, that synthetic serum substitute also activates transcription of genes related to adipogenic and osteogenic differentiation and diminishes expression of cell surface marker CD146. In the present study, we used a proteomic approach that allowed us to compare protein expression signatures between primary cell culture and her daughter clones. As a result, we for the first time established a map of abundantly expressed proteins in MSC-like cells derived from the dental pulp of human exfoliated deciduous teeth. We also demonstrate that physiological and inflammatory concentrations of human alpha1-antitrypsin increase the proliferation and motility of mesenchymal stem cells derived from exfoliated deciduous tooth. Results of the present study extend our understanding of processes in MSCs during cultivation in vitro and explain some mechanisms responsible for the functionality of these cells