MESENCHYMAL STEM CELL SECRETOME DECREASES THE INFLAMMATORY RESPONSE IN ANNULUS FIBROSUS ORGAN CULTURES

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Neidlinger Wilke, C (Author) Other; Ekkerlein, A (Author) Other; Goncalves, RM (Author) ICBAS; Ferreira, JR (Author) Other; Ignatius, A (Author) Other; Wilke, HJ (Author) Other; Teixeira, GQ (Author) Other

Journal

Title: European Cells and Materials

Vol. 42

Pages: 1-19

ISSN: 1473-2262

Publisher: AO Research Institute Davos

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 9 Citations

Other information

Authenticus ID: P-00V-981

DOI: 10.22203/ecm.v042a01

Abstract (EN): Mesenchymal stem/stromal cell (MSC)-based therapies have been proposed for back pain and discdegeneration, despite limited knowledge on their mechanism of action. The impact of MSCs/their secretomeon annulus fibrosus (AF) cells and tissue was analysed in bovine AF organ cultures (AF-OCs) exposed toupper-physiological cyclic tensile strain (CTS, 9 %, 1 Hz, 3 h/d) and interleukin (IL)-1 beta in a custom-made device. A 4 d treatment of the CTS + IL-1 beta-stimulated AF-OCs with MSC secretome downregulated the expression of inflammation markers [IL-6, IL-8, prostaglandin-endoperoxide synthase 2 (PTGS2)], complement system regulators [cluster of differentiation (CD)46, CD55, CD59] and matrix metalloproteinase 1 but alsoof tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and collagen type I. At the protein level, it was confirmed that IL-6, MMP-3 and collagen content was decreased in AF-OCs treated with the MSC secretome compared to the CTS + IL-1 beta stimulation alone. 9 d after treatment, a biomechanical peel-force test showed that the annular adhesive strength was significantly decreased by the MSC secretome treatment. Overall, MSC secretome had a stronger impact on AF tissue than MSCs in co-culture. The secretome contributed to a decrease in the inflammatory and catabolic status of AF cells activated by CTS + IL-1 beta and played a role in the regulation of the complement system. However, it also contributed to a decrease in collagen at the gene/protein level and in AF mechanical strength compared to the CTS + IL-1 beta stimulation alone. Therefore, the use of MSC secretome requires further investigation regarding its influence on disc matrix properties.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 19