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University of Groningen

Bridging the gap

Spiekman, Maroesjka

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from

it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date:

2018

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Spiekman, M. (2018). Bridging the gap: Adipose tissue-based therapy for dermal scarring. Rijksuniversiteit

Groningen.

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Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.

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Bridging the gap

Adipose tissue-based therapy for dermal scarring

Proefschrift

ter verkrijging van de graad van doctor aan de

Rijksuniversiteit Groningen

op gezag van de

rector magnificus prof. dr. E. Sterken

en volgens besluit van het College voor Promoties.

De openbare verdediging zal plaatsvinden op

woensdag 20 juni 2018 om 12.45 uur

door

Maroesjka Spiekman

geboren op 11 augustus 1990

te Groningen

For publication of this thesis, financial support from the Graduate School of Medical Sciences of the University of Groningen / University Medical Center Groningen, Human Med AG, Schwerin, Germany and BlooMEDical Benelux BV is gratefully acknowledged.

The research in this thesis was supported by the University Medical Center Groningen, University of Groningen and by grants from the Junior Scientific Masterclass, The Ubbo Emmius Fund, Jan Kornelis de Cock Foundation and Foundation ‘De Drie Lichten’.

Spiekman, Maroesjka

Bridging the gap: Adipose tissue-based therapy for dermal scarring ISBN: 978-94-034-0664-0

ISBN: 978-94-034-0663-3 / elektronische versie Cover design: H.W. Spiekman

Lay-out: Rozemarijn Klein Heerenbrink, PersoonlijkProefschrift.nl Printed by: Ipskamp Printing B.V.

© Maroesjka Spiekman

All rights reserved. No part of this publication may be reproduced, stored on a retrieval system, or transmitted in any form or by any means, without permission of the author.

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Promotores

Prof. dr. M.C. Harmsen Prof. dr. B. van der Lei

Copromotor

Dr. G. Krenning

Beoordelingscommissie

Prof. dr. M.F. Jonkman Prof. dr. R.A. Bank Prof. dr. P.P.M. Zuijlen

Paranimfen

Marloes A.M. Peters Byambasuren Vanchin

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TABLE OF CONTENTS

CHAPTER 1 Introduction and outline 9

CHAPTER 2 The power of fat and its adipose-derived stromal cells: emerging concepts for fibrotic scar treatment

31

CHAPTER 3 Autologous lipofilling improves clinical outcome in patients with symptomatic dermal scars through induction of a pro-regenerative immune response

63

CHAPTER 4 A comparison of intraoperative procedures for isolation of clinical grade stromal vascular fraction for regenerative purposes: a systematic review

93

CHAPTER 5 The role of stromal vascular fraction in scar prevention: a model for a well-designed prospective double blind randomized placebo-controlled clinical trial

131

CHAPTER 6 Platelet-Rich Plasma (PRP) influences expansion and paracrine function of adipose-derived stromal cells (ADSC) in a dose-dependent fashion

147

CHAPTER 7 Adipose tissue-derived stromal cells inhibit TGF-β1-induced differentiation of human dermal fibroblasts and keloid scar-derived fibroblasts in a paracrine fashion

169

CHAPTER 8 MicroRNA-15b is decreased during cardiac fibrosis and inhibits cardiac fibroblast activation through targeting of the small GTPase intermediates Growth Factor Receptor-Bound 2 (Grb2) and Son-of- Sevenless homologue (SOS) 1 and SOS2

189

CHAPTER 9 Research summary and general discussion

215

CHAPTER 10 Nederlandse samenvatting

243

APPENDICES Abbreviations Curriculum vitae Grants & Awards Presentations & Lectures List of publications Dankwoord

250

254

256

256

257

258

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