Engineered extracellular matrix components do not
alter the immunomodulatory properties of
mesenchymal stromal cells in vitro
Rebekka Wehner
1
, Christina Taubert
1
, Tanja Mende
1
, Christian Gaebler
1
,
Ana Valeria Gouveia de Andrade
2,3
, Martin Bornhäuser
2,4
, Carsten Werner
2,5
, Torsten Tonn
2,3,6
,
Knut Schäkel
7
, Michael Bachmann
1,2
and Marc Schmitz
1,2
*
1
Institute of Immunology, Technical University of Dresden, Germany
2
Centre for Regenerative Therapies Dresden, Germany
3
German Red Cross Blood Service, Dresden, Germany
4
Department of Medicine I, University Hospital of Dresden, Germany
5
Leibniz Institute for Polymer Research, Max Bergmann Center of Biomaterials, Dresden, Germany
6
Experimental Transfusion Medicine, Medical Faculty, Technical University of Dresden, Germany
7
Department of Dermatology, University Hospital of Heidelberg, Germany
Abstract
Mesenchymal stromal cells (MSCs) have emerged as promising candidates for regenerative therapies,
including tissue engineering. Recently it has been reported that engineered extracellular matrix
(ECM) components support the differentiation of MSCs into osteocytes and chondrocytes, indicating
that ECM components may represent attractive carriers for MSC transplants to repair damaged tissues.
However, little is known about the impact of engineered ECM components on the immunosuppressive
properties of MSCs, which may essentially contribute to the prevention of allogeneic MSC transplant
rejection. In the present study, we explored the potential of fibronectin, fibrillar collagen I, tropocolla-
gen and collagen I/heparin to influence the immunosuppressive capacities of MSCs. We found that these
ECM components do not modulate the capability of MSCs to inhibit the proliferation of anti-CD3/anti-
CD28 antibody-stimulated CD4
+
and CD8
+
T cells and of lymphocytes in a mixed lymphocyte reaction.
In addition, the potential of MSCs to impair the production of immunostimulatory IL-12 and to improve
the release of immunosuppressive IL-10 by 6-sulpho LacNAc
+
(slan) dendritic cells (DCs), representing
a pro-inflammatory subset of human blood DCs, was not altered by the ECM components. Furthermore,
ECM components do not influence the ability of MSCs to inhibit the slanDC-induced proliferation of
CD4
+
T cells. In conclusion, the used engineered ECMs maintain important immunosuppressive
properties of MSCs, which support their suitablility as carriers for MSC transplants in tissue engineering.
Copyright © 2012 John Wiley & Sons, Ltd.
Received 7 March 2011; Revised 11 November 2011; Accepted 24 January 2012
Keywords mesenchymal stromal cells; extracellular matrix components; T lymphocytes; dendritic cells
Bone marrow-derived mesenchymal stromal cells (MSCs)
represent a population of non-haematopoietic cells with a
high capability to differentiate into various cell types such
as osteocytes and chondrocytes (Pittenger et al., 1999).
Due to their differentiation capability, MSCs emerge as
attractive candidates for therapeutic applications in
tissue engineering (Arthur et al., 2009). In this context,
a promising strategy employs engineered extracellular
matrix (ECM) components as carriers for MSC transplants
to repair damaged tissues. Recently, it has been demon-
strated that various ECM components maintain the viabil-
ity of MSCs and support their capacity to differentiate into
osteocytes and chondrocytes (Kundu and Putnam, 2006;
Lanfer et al., 2009; Seib et al., 2009). However, studies
investigating the impact of ECM components on the
profound immunosuppressive properties of MSCs, which
may play an important role in the prevention of allogeneic
MSC transplant rejection, are rather limited. Thus, it has
*Correspondence to: M. Schmitz, Institute of Immunology, Medical
Faculty, Technical University of Dresden, Fetscherstrasse 74, 01307
Dresden, Germany. E-mail: marc.schmitz@tu-dresden.de
Copyright © 2012 John Wiley & Sons, Ltd.
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE SHORT COMMUNICATION
J Tissue Eng Regen Med (2012)
Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/term.1500