- Author
-
A.S.M. Cornelissen
- Title
- The versatility of mesenchymal stromal cells
- Subtitle
- Means for optimization
- Supervisors
-
C.E. van der Schoot
- Co-supervisors
-
C. Voermans
- Award date
- 7 May 2019
- Number of pages
- 247
- ISBN
- 9789463235167
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
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.
- Persistent Identifier
- https://hdl.handle.net/11245.1/5f545d81-f246-449e-ba55-028c76ca1381
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: General introduction and scope of the thesis
Chapter 2: Organ-specific migration of mesenchymal stromal cells: Who, when, where and why?
Chapter 3: Migratory behaviour and biodistribution of human mesenchymal stromal cells is limited by imbalanced nuclear-cytoskeletal coupling
Chapter 4: Means to optimize mesenchymal stromal cells for immunomodulation
Chapter 5: Interferon-gamma impairs maintenance and alters hematopoietic support of bone marrow mesenchymal stromal cells
Chapter 6: Mesenchymal stromal cells stimulate the proliferation and interleukin-22 production of group 3 innate lymphoid cells
Chapter 7: Nucleosome levels are increased in acute graft-versus-host disease in patients and mice
Chapter 8: General discussion
English summary; Nederlandse samenvatting; List of publications; List of co-authors and their contribution to the manuscript; PhD portfolio; Curriculum vitae; Dankwoord
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