TY - JOUR A1 - Herrmann, Marietta A1 - Diederichs, Solvig A1 - Melnik, Svitlana A1 - Riegger, Jana A1 - Trivanović, Drenka A1 - Li, Shushan A1 - Jenei-Lanzl, Zsuzsa A1 - Brenner, Rolf E. A1 - Huber-Lang, Markus A1 - Zaucke, Frank A1 - Schildberg, Frank A. A1 - Grässel, Susanne T1 - Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration JF - Frontiers in Bioengineering and Biotechnology N2 - The incidence of musculoskeletal diseases is steadily increasing with aging of the population. In the past years, extracellular vesicles (EVs) have gained attention in musculoskeletal research. EVs have been associated with various musculoskeletal pathologies as well as suggested as treatment option. EVs play a pivotal role in communication between cells and their environment. Thereby, the EV cargo is highly dependent on their cellular origin. In this review, we summarize putative mechanisms by which EVs can contribute to musculoskeletal tissue homeostasis, regeneration and disease, in particular matrix remodeling and mineralization, pro-angiogenic effects and immunomodulatory activities. Mesenchymal stromal cells (MSCs) present the most frequently used cell source for EV generation for musculoskeletal applications, and herein we discuss how the MSC phenotype can influence the cargo and thus the regenerative potential of EVs. Induced pluripotent stem cell-derived mesenchymal progenitor cells (iMPs) may overcome current limitations of MSCs, and iMP-derived EVs are discussed as an alternative strategy. In the last part of the article, we focus on therapeutic applications of EVs and discuss both practical considerations for EV production and the current state of EV-based therapies. KW - extracellular vesicles KW - exosomes KW - musculoskeletal diseases KW - MSC KW - iMP KW - cell-free therapeutics Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222882 SN - 2296-4185 VL - 8 ER - TY - JOUR A1 - Schwab, Andrea A1 - Buss, Alexa A1 - Pullig, Oliver A1 - Ehlicke, Franziska T1 - Ex vivo osteochondral test system with control over cartilage defect depth – A pilot study to investigate the effect of oxygen tension and chondrocyte based treatments in chondral and full thickness defects in an organ model JF - Osteoarthritis and Cartilage Open N2 - Objective Cartilage defect treatment strategies are dependent on the lesion size and severity. Osteochondral explant models are a platform to test cartilage repair strategies ex vivo. Current models lack in mimicking the variety of clinically relevant defect scenarios. In this controlled laboratory study, an automated device (artificial tissue cutter, ARTcut®) was implemented to reproducibly create cartilage defects with controlled depth. In a pilot study, the effect of cartilage defect depth and oxygen tension on cartilage repair was investigated. Design Osteochondral explants were isolated from porcine condyles. 4 ​mm chondral and full thickness defects were treated with either porcine chondrocytes (CHON) or co-culture of 20% CHON and 80% MSCs (MIX) embedded in collagen hydrogel. Explants were cultured with tissue specific media (without TGF-β) under normoxia (20% O\(_2\)) and physiological hypoxia (2% O\(_2\)). After 28 days, immune-histological stainings (collagen II and X, aggrecan) were scored (modified Bern score, 3 independent scorer) to quantitatively compare treatment outcome. Results ARTcut® represents a software-controlled device for creation of uniform cartilage defects. Comparing the scoring results of the MIX and the CHON treatment, a positive relation between oxygen tension and defect depth was observed. Low oxygen tension stimulated cartilaginous matrix deposition in MIX group in chondral defects and CHON treatment in full thickness defects. Conclusion ARTcut® has proved a powerful tool to create cartilage defects and thus opens a wide range of novel applications of the osteochondral model, including the relation between oxygen tension and defect depth on cartilage repair. KW - cartilage defectex vivo model KW - cartilage test system KW - chondrocytes KW - MSC KW - collagen type I hydrogel Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260511 VL - 3 IS - 2 ER -