The Extracellular Matrix for Bone Regeneration:
Interplay between Mesenchymal Stromal Cells and the
Bone Microenvironment
The work presented in this thesis was performed in the Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. This work was financially supported by a grant from the Dutch government to the Netherlands Institute of Regenerative Medicine (FES0908). The studies described in Chapter 2 were performed in collaboration with the Department of Precision and Microengi-neering and the Department of Biomechanical EngiMicroengi-neering of Delft University of Technology. The studies described in Chapter 2 and 3 were performed in collabora-tion with the Proteomics Center of Erasmus MC. The studies described in Chapter 5 were performed in close collaboration with the Department of Gastroenterology and Hepatology of Erasmus MC and supported by European Commission FP7 Program INTERBONE Grant PIRSES-GA-2011-295181, Erasmus Trustfonds and Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) (grant No: 2014/22689-3). ISBN: 978-94-6361-105-3
Copyright © 2018 Marta Baroncelli
All rights reserved. For all articles published or accepted the copyright has been transferred to the respective publisher. No part of this thesis may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, without prior written permission of the author.
Cover by Anita Faggi, depicting mesenchymal stromal cells in the starry night. Mesenchymal stromal cells in culture, image by Marta Baroncelli. The Starry Night: image adapted from www.pixabay.com (The Starry Night (1889) by Vincent van Gogh (1853-1890), Museum of Modern Art (MoMA), New York, USA).
Chapter figure: scanning electron microscopy image of the osteoblast-derived extra-cellular matrix by Ingmar van Hengel
Layout and printing: Optima Grafische Communicatie, Rotterdam, The Netherlands Publication of this thesis was supported by Erasmus University Rotterdam and by Netherlands Society for Biomaterials and Tissue Engineering (NBTE).
The Extracellular Matrix for Bone Regeneration:
Interplay between mesenchymal stromal cells and the
bone microenvironment
Extracellulaire Matrix voor Botregeneratie:
Interactie tussen mesenchymale stromale cellen en de bot-omgeving
Thesis
to obtain the degree of Doctor at Erasmus University Rotterdam
on the authority of the rector magnificus Prof. Dr. H.A.P Pols
and in accordance with the decision of the Doctorate Board. The public defence ceremony shall be held on
Wednesday, 13 June 2018 at 09:30 hours by
Marta Baroncelli born in Prato, Italy
DoCToRal CoMMITTEE
Supervisor: Prof. Dr. J.P.T.M van Leeuwen other members: Prof. Dr. G.J.V.M van Osch
Prof. Dr. J. de Boer Prof. Dr. L.J. Hofland Co-supervisor: Dr. ing. H.J. van de Peppel
TaBlE of ConTEnTS
Chapter 1 General Introduction 9
Chapter 2 Human osteoblast-derived extracellular matrix with high homology to bone proteome is osteopromotive
39
Chapter 3 Comparative proteomic profiling of human osteoblast-derived extracellular matrices identifies proteins involved in mesenchymal stromal cell osteogenic differentiation and mineralization
73
Chapter 4 A single two-day-pulse of Activin-A leads to a transient change in osteoblast gene expression and reduction in extracellular matrix mineralization
127
Chapter 5 Human mesenchymal stromal cells in adhesion to cell-derived extracellular matrix and titanium: a comparative kinome profile analysis
163
Chapter 6 General Discussion 221
Appendix Abbreviation index 240
Summary 245 Samenvatting 248 Curriculum Vitae 251 Ph.D portfolio 252 Publications 254 Acknowledgements 256
