Mesenchymal stem cell secretome decreases the inflammatory response in annulus fibrosus organ cultures

European Cells & Materials

article

GQ Teixeira¹  HJ Wilke¹  A Ignatius¹  JR Ferreira¹  RM Goncalves²  A Ekkerlein¹  C Neidlinger-Wilke¹ 

[1]Institute of Orthopaedic Research and Biomechanics, Trauma Research Centre, Ulm University

[2]Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto

[3]Instituto de Engenharia Biomédica (INEB), Universidade do Porto

[4]Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto

关键词: Intervertebral disc;    degeneration;    herniation;    repair/regeneration;    mechanical loading;    inflammation;    complement;    paracrine signalling.;   

DOI  :  10.22203/eCM.v042a01

学科分类：内科医学

来源: Swiss Society for Biomaterials

【 摘 要 】

Mesenchymal stem/stromal cell (MSC)-based therapies have been proposed for back pain and disc degeneration, despite limited knowledge on their mechanism of action. The impact of MSCs/their secretome on annulus fibrosus (AF) cells and tissue was analysed in bovine AF organ cultures (AF-OCs) exposed to upper-physiological cyclic tensile strain (CTS, 9 %, 1 Hz, 3 h/d) and interleukin (IL)-1β in a custom-made device. A 4 d treatment of the CTS + IL-1β-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 also of 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-1β 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-1β 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-1β stimulation alone. Therefore, the use of MSC secretome requires further investigation regarding its influence on disc matrix properties.

【 授权许可】

CC BY-SA