Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/18207
Title: Human Wharton's jelly-derived stem cells display immunomodulatory properties and transiently improve rat experimental autoimmune encephalomyelitis.
Authors: DONDERS, Raf 
VANHEUSDEN, Marjan 
BOGIE, Jeroen 
RAVANIDIS, Stelios 
THEWISSEN, Kristof 
STINISSEN, Piet 
GYSELAERS, Wilfried 
HENDRIKS, Jerome 
HELLINGS, Niels 
Issue Date: 2014
Source: CELL TRANSPLANTATION, 24 (10), p. 2077-2098
Abstract: Umbilical cord matrix or Wharton?s jelly-derived stromal cells (WJ-MSCs) are an easily accessible source of mesenchymal-like stem cells. Recent studies describe a hypo-immunogenic phenotype, multipotent differentiation potential and trophic support function for WJ-MSCs, with variable clinical benefit in degenerative disease models such as stroke, myocardial infarction and Parkinson?s disease. It remains unclear whether WJ-MSCs have therapeutic value for multiple sclerosis (MS), where autoimmune-mediated demyelination and neurodegeneration need to be halted. In this study, we investigated whether WJ-MSCs possess the required properties to effectively and durably reverse these pathological hallmarks, and whether they survive in an inflammatory environment after transplantation. WJ-MSCs displayed a lowly immunogenic phenotype and showed intrinsic expression of neurotrophic factors and a variety of anti-inflammatory molecules. Furthermore, they dose-dependently suppressed proliferation of activated T cells using contact-dependent and paracrine mechanisms. Indoleamine 2,3-dioxygenase 1 was identified as one of the main effector molecules responsible for the observed T cell suppression. The immune-modulatory phenotype of WJ-MSCs was further enhanced after pro-inflammatory cytokine treatment in vitro (licensing). In addition to their effect on adaptive immunity, WJ-MSCs interfered with dendritic cell differentiation and maturation, thus directly affecting antigen presentation and therefore T cell priming. Systemically infused WJ-MSCs potently but transiently ameliorated experimental autoimmune encephalomyelitis (EAE), an animal model for MS, when injected at onset or during chronic disease. This protective effect was paralleled with a reduction in autoantigen-induced T cell proliferation, confirming their immune-modulatory activity in vivo. Surprisingly, in vitro licensed WJ-MSCs did not ameliorate EAE, indicative of a fast rejection as a result of enhanced immunogenicity. Collectively, we show that WJ-MSCs have trophic support properties and effectively modulate immune cell functioning both in vitro and in the EAE model, suggesting WJ-MSC may hold promise for MS therapy. Future research is needed to optimize survival of stem cells and enhance clinical durability.
Notes: Hellings, N (reprint author), Hasselt Univ, Biomed Res Inst, Campus Diepenbeek,Agoralaan Bldg C, B-3590 Diepenbeek, Belgium. niels.hellings@uhasselt.be
Keywords: cell therapy; immunomodulation; mesenchymal stem cells (MSCs); Multiple Sclerosis; transplantation; Wharton’s jelly
Document URI: http://hdl.handle.net/1942/18207
ISSN: 0963-6897
e-ISSN: 1555-3892
DOI: 10.3727/096368914X685104
ISI #: 000362861200013
Rights: Copyright © 2014 Cognizant Communication Corporation
Category: A1
Type: Journal Contribution
Validations: ecoom 2016
Appears in Collections:Research publications

Files in This Item:
File Description SizeFormat 
ct-1266_donders_et_al_1412946660552.pdf
  Restricted Access
Peer-reviewed author version1.55 MBAdobe PDFView/Open    Request a copy
096368914x685104.pdfPublished version1.64 MBAdobe PDFView/Open
Show full item record

SCOPUSTM   
Citations

42
checked on Sep 5, 2020

WEB OF SCIENCETM
Citations

60
checked on Mar 29, 2024

Page view(s)

84
checked on Aug 31, 2022

Download(s)

158
checked on Aug 31, 2022

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.