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The handle http://hdl.handle.net/1887/38545 holds various files of this Leiden University dissertation.

Author: Molendijk, Ilse

Title: Mesenchymal stromal cell therapy for Crohn's disease : from perianal fistulizing disease to experimental colitis

Issue Date: 2016-03-15

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Mesenchymal stromal cell therapy for Crohn’s disease

from perianal fistulizing disease to experimental colitis

Ilse Molendijk

(3)

Cover design: Eveline de Jonge – Muller Cover photograph: Willem Vermaase

Printed by: Uitgeverij BOXPress || Proefschriftmaken.nl ISBN: 978-94-6295-452-6

© 2016, I. Molendijk, Leiden, the Netherlands

All rights reserved. No part of this thesis may be reproduced or transmitted in any form or by any means without prior written permission of the author.

The research described in this thesis was financially supported by a grant from the DigestScience Foundation.

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties te verdedigen op dinsdag 15 maart 2016

klokke 15:00 uur door

Ilse Molendijk

geboren te Gouda in 1985 Financial support for the publication of this thesis was kindly provided by AbbVie B.V.,

ABN AMRO, BD Biosciences, ChipSoft B.V., Dr. Falk Pharma Benelux B.V., EuroTec B.V.,

Greiner Bio-One B.V., Dutch Society of Gastroenterology (NVGE), Olympus Nederland

B.V., Section Experimental Gastroenterology (SEG) of the Dutch Society of Gas-

troenterology (NVGE), Stöpler Instrumenten & Apparaten B.V., Takeda Nederland B.V.

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Cover design: Eveline de Jonge – Muller Cover photograph: Willem Vermaase

Printed by: Uitgeverij BOXPress || Proefschriftmaken.nl

ISBN: 978-94-6295-452-6

© 2016, I. Molendijk, Leiden, the Netherlands

All rights reserved. No part of this thesis may be reproduced or transmitted in any form or by any means without prior written permission of the author.

Financial support for the publication of this thesis was kindly provided by

The research described in this thesis was financially supported by a grant from the DigestScience Foundation.

Mesenchymal stromal cell therapy for Crohn’s disease

from perianal fistulizing disease to experimental colitis

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties te verdedigen op dinsdag 15 maart 2016

klokke 15:00 uur door

Ilse Molendijk

geboren te Gouda

in 1985

(5)

Prof. dr. W.E. Fibbe

Prof. dr. D.E. Atsma

Dr. B.A. Bonsing

(6)

Promotores Prof. dr. ir. H.W. Verspaget Prof. dr. D.W. Hommes

Co-promotor Mw. dr. A.E. van der Meulen – de Jong

Leden promotiecommissie Mw. prof. dr. C.J. van der Woude, Erasmus MC Rotterdam Prof. dr. G. Dijkstra, UMCG Groningen

Prof. dr. W.E. Fibbe

Prof. dr. D.E. Atsma

Dr. B.A. Bonsing

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Chapter 2 Outline and aims of the studies described in this thesis 32

Chapter 3 Disappointing durable remission rates in complex Crohn’s 36 disease fistula

Inflammatory Bowel Diseases. 2014;20:2022-2028

Chapter 4 Allogeneic bone marrow-derived mesenchymal stromal 54 cells promote healing of refractory perianal fistulas in pa-

tients with Crohn’s disease

Gastroenterology. 2015;149:918-927

Chapter 5 Standardization of local treatment for perianal fistulizing 80 Crohn’s disease

Submitted

Chapter 6 Time of administration and disease severity are key factors 98 in achieving efficacy of human bone marrow-derived mesen-

chymal stromal cells in an experimental model of colitis

Manuscript in preparation

Chapter 7 VCAM-dependent migration of IFNɣ- and TNFα-stimulated 120 mesenchymal stromal cells ameliorates TNBS-induced colitis

Manuscript in preparation

Chapter 8 Intraluminal injection of mesenchymal stromal cells in 146 spheroids attenuates experimental colitis

Submitted

Chapter 9 Summary and discussion 172

Dankwoord

List of abbreviations

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T ABLE OF CONTENTS

Chapter 1 Introduction 8

Best Practice & Research: Clinical Gastroenterology. 2014;28:505-518, In: Mesenchymal stem cell therapy. 2013; Springer text book and J Allergy (Cairo). 2012;2012:187408

Chapter 2 Outline and aims of the studies described in this thesis 32

Chapter 3 Disappointing durable remission rates in complex Crohn’s 36 disease fistula

Inflammatory Bowel Diseases. 2014;20:2022-2028

Chapter 4 Allogeneic bone marrow-derived mesenchymal stromal 54 cells promote healing of refractory perianal fistulas in pa-

tients with Crohn’s disease

Gastroenterology. 2015;149:918-927

Chapter 5 Standardization of local treatment for perianal fistulizing 80 Crohn’s disease

Submitted

Chapter 6 Time of administration and disease severity are key factors 98 in achieving efficacy of human bone marrow-derived mesen-

chymal stromal cells in an experimental model of colitis

Manuscript in preparation

Chapter 7 VCAM-dependent migration of IFNɣ- and TNFα-stimulated 120 mesenchymal stromal cells ameliorates TNBS-induced colitis

Manuscript in preparation

Chapter 8 Intraluminal injection of mesenchymal stromal cells in 146 spheroids attenuates experimental colitis

Submitted

Chapter 9 Summary and discussion 172

Chapter 10 Nederlandse samenvatting 184

Chapter 11 List of publications 190

Curriculum Vitae Dankwoord

List of abbreviations

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