Human mesenchymal stromal cells : biological characterization and clinical application
Bernardo, M.E.
Citation
Bernardo, M. E. (2010, March 4). Human mesenchymal stromal cells : biological
characterization and clinical application. Retrieved from https://hdl.handle.net/1887/15034
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden
Downloaded from: https://hdl.handle.net/1887/15034
Note: To cite this publication please use the final published version (if applicable).
253 Summary in English
This thesis focuses on the characterization of the biological and functional properties of human mesenchymal stromal cells (MSCs), isolated from different tissue sources. The differentiation capacity of MSCs from fetal and adult tissues has been tested and compared. Umbilical cord blood (UCB) has been investigated as a potential novel source of MSCs for clinical application and the immunomodulatory properties of UCB-derived MSCs have been characterized in comparison with those of MSCs of bone marrow (BM) origin.
Moreover, it has been attempted to optimize the experimental conditions for MSC ex vivo expansion. Alternative culture methods, devoid of animal proteins, have been applied by introducing expansion procedures based on platelet-derived growth factors. The potential susceptibility of MSCs to undergo malignant transformation after long-term in vitro culture has been investigated and discussed in view of their clinical application, especially in immunocompromised hosts. The immunogenicity of the cells and/or their medium components, the risk of ectopic tissue formation and that of MSC- mediated immunosuppression have been also discussed as potential risks associated with the clinical use of ex vivo expanded MSCs.
The lack of surface markers and functional assays to specifically identify MSCs and to facilitate the generation of homogenous cell products has been analyzed and efforts for future MSC development have been discussed. Novel techniques, such as proteomic approaches and microarray analysis, have been proposed with the aim to improve the knowledge on MSC biological and functional properties; imaging studies, based on the use of suitable labeling techniques and able to investigate in vivo MSC ‘trafficking’ and biodistribution, have been discussed.
The role of MSC therapy in the context of hematopoietic stem cell transplantation (HSCT) has been explored, focusing in particular on the co-
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transplantation of MSCs to promote engraftment of hematopoietic progenitors, and on the administration of MSCs for the treatment of steroid-resistant, severe acute graft-versus-host disease (GvHD). The role of MSCs in the treatment of inflammatory bowel diseases refractory to conventional therapies, as well as the concept for treating refractory autoimmune diseases has been discussed. In particular, the potential role of autologous BM-derived MSCs as immunomodulatory/anti-inflammatory treatment to stimulate tissue repair in Crohn’s Disease (CD) patients has been investigated. Based on these experimental and clinical findings and by broadening the knowledge on MSC biological activities, these cells could be employed in the near future as a novel therapeutic strategy to stimulate tissue repair and modulate immune responses in a variety of immune-mediated and inflammatory diseases.
