Thesis Anne Cornelissen

Summary

Mesenchymal stromal cells (MSC) are multipotent cells that can be derived from various adult and fetal tissues. The clinical interest in MSC has grown enormously as research revealed that these cells possess hematopoietic supporting, regenerative and immunomodulatory capacities. Due to the low frequency of MSC in the human body, it is necessary to massively expand MSC in order to obtain sufficient cell numbers for clinical application. The biggest hurdle is that this ex vivo expansion drastically decreases therapeutic efficacy. Another problem the field is facing is the heterogeneity of MSC on several levels: cell-intrinsic differences, tissue-specific heterogeneity and differences in culture media and/or stimulation methods. In this thesis, we aimed to investigate and improve the desired and clinically important properties of MSC such as migration, immunomodulation and hematopoietic support. Moreover, the role of MSC in Graft-versus-Host disease, their interaction with other immune cells and GvHD pathology itself have been addressed. The results presented in this thesis will contribute to the understanding of the biological roles of MSC in hematopoietic support and immunomodulation, in particular GvHD. Furthermore, it describes different approaches to further improve the biological function of MSC with the aim to optimize therapeutic efficacy.