TY  - JOUR
A1  - Frischholz, Sebastian
A1  - Berberich, Oliver
A1  - Böck, Thomas
A1  - Meffert, Rainer H.
A1  - Blunk, Torsten
T1  - Resveratrol counteracts IL‐1β‐mediated impairment of extracellular matrix deposition in 3D articular chondrocyte constructs
JF  - Journal of Tissue Engineering and Regenerative Medicine
N2  - When aiming at cell‐based therapies in osteoarthritis (OA), proinflammatory conditions mediated by cytokines such as IL‐1β need to be considered. In recent studies, the phytoalexin resveratrol (RSV) has exhibited potent anti‐inflammatory properties. However, long‐term effects on 3D cartilaginous constructs under inflammatory conditions with regard to tissue quality, especially extracellular matrix (ECM) composition, have remained unexplored. Therefore, we employed long‐term model cultures for cell‐based therapies in an in vitro OA environment and evaluated effects of RSV. Pellet constructs made from expanded porcine articular chondrocytes were cultured with either IL‐1β (1–10 ng/ml) or RSV (50 μM) alone, or a cotreatment with both agents. Treatments were applied for 14 days, either directly after pellet formation or after a preculture period of 7 days. Culture with IL‐1β (10 ng/ml) decreased pellet size and DNA amount and severely compromised glycosaminoglycan (GAG) and collagen content. Cotreatment with RSV distinctly counteracted the proinflammatory catabolism and led to partial rescue of the ECM composition in both culture systems, with especially strong effects on GAG. Marked MMP13 expression was detected in IL‐1β‐treated pellets, but none upon RSV cotreatment. Expression of collagen type I was increased upon IL‐1β treatment and still observed when adding RSV, whereas collagen type X, indicating hypertrophy, was detected exclusively in pellets treated with RSV alone. In conclusion, RSV can counteract IL‐1β‐mediated degradation and distinctly improve cartilaginous ECM deposition in 3D long‐term inflammatory cultures. Nevertheless, potential hypertrophic effects should be taken into account when considering RSV as cotreatment for articular cartilage repair techniques.
KW  - articular chondrocytes
KW  - cartilage
KW  - cell‐based therapy
KW  - extracellular matrix
KW  - IL‐1β
KW  - inflammation
KW  - osteoarthritis
KW  - resveratrol
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215471
VL  - 14
IS  - 7
SP  - 897
EP  - 908
ER  - 
TY  - JOUR
A1  - Schmidt, Stefanie
A1  - Abinzano, Florencia
A1  - Mensinga, Anneloes
A1  - Teßmar, Jörg
A1  - Groll, Jürgen
A1  - Malda, Jos
A1  - Levato, Riccardo
A1  - Blunk, Torsten
T1  - Differential production of cartilage ECM in 3D agarose constructs by equine articular cartilage progenitor cells and mesenchymal stromal cells
JF  - International Journal of Molecular Sciences
N2  - Identification of articular cartilage progenitor cells (ACPCs) has opened up new opportunities for cartilage repair. These cells may be used as alternatives for or in combination with mesenchymal stromal cells (MSCs) in cartilage engineering. However, their potential needs to be further investigated, since only a few studies have compared ACPCs and MSCs when cultured in hydrogels. Therefore, in this study, we compared chondrogenic differentiation of equine ACPCs and MSCs in agarose constructs as monocultures and as zonally layered co-cultures under both normoxic and hypoxic conditions. ACPCs and MSCs exhibited distinctly differential production of the cartilaginous extracellular matrix (ECM). For ACPC constructs, markedly higher glycosaminoglycan (GAG) contents were determined by histological and quantitative biochemical evaluation, both in normoxia and hypoxia. Differential GAG production was also reflected in layered co-culture constructs. For both cell types, similar staining for type II collagen was detected. However, distinctly weaker staining for undesired type I collagen was observed in the ACPC constructs. For ACPCs, only very low alkaline phosphatase (ALP) activity, a marker of terminal differentiation, was determined, in stark contrast to what was found for MSCs. This study underscores the potential of ACPCs as a promising cell source for cartilage engineering.
KW  - ACPC
KW  - chondroprogenitors
KW  - tissue engineering
KW  - MSC
KW  - agarose
KW  - hypoxia
KW  - ECM
KW  - co-culture
KW  - zonal
KW  - cartilage
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236180
SN  - 1422-0067
VL  - 21
IS  - 19
ER  -