IL-1 beta-PRE-CONDITIONED MESENCHYMAL STEM/STROMAL CELLS' SECRETOME MODuLA TES THE INFLAMMATORY RESPONSE AND AGGRECAN DEPOSITION IN THE INTERVERTEBRAL DISC

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

Authors

Ferreira, J (Author) Other; Teixeira, GQ (Author) Other; Neto, E (Author) Other; Ribeiro Machado, C (Author) Other; Silva, AM (Author) Other; Caldeira, J (Author) Other; Pereira, CL (Author) Other; Bidarra, S (Author) Other; Maia, AF (Author) Other; Lamghari, M (Author) Other; Barbosa, MM (Author) Other; Goncalves, RM (Author) ICBAS

Journal

Title: European Cells and Materials

Vol. 41

Pages: 431-453

ISSN: 1473-2262

Publisher: AO Research Institute Davos

Indexing

ISI Web of Knowledge - 19 Citations

Scopus - 20 Citations

Other information

Authenticus ID: P-00T-YEX

DOI: 10.22203/ecm.v041a28

Abstract (EN): Mesenchymal stem/stromal cells (MSCs) have been increasingly used in clinical trials for low-back pain (LBP) and intervertebral disc (IVD) degeneration with promising results. Their action mechanisms are not fully understood, but they reduce IVD pro-inflammatory markers in a pro-inflammatory/degenerative IVD microenvironment. In this study the therapeutic potential of the MSC secretome, as an alternative cell-free approach for treating degenerated IVDs, was examined. Human bone marrow-derived MSC secretome (MSCsec) was collected after 48 h of preconditioning in IL-1 beta (10 ng/mL) and low oxygen (6 % O-2), mimicking the degenerative IVD. IL-1 beta-pre-conditioning of MSCs increased secretion of pro-inflammatory markers hIL-6, hIL-8, hMCP-1, etc. The therapeutic effect of MSCsec was tested in a pro-inflammatory/degenerative IVD ex vivo model. MSCsec down-regulated IVD gene expression of pro-inflammatory cytokines (bIL-6, bIL-8) and matrix degrading enzyme bMMP1, while bMMP3 and bTIMP2 were up-regulated, at 48 h. After 14 d, MSCsec-treated IVDs revealed increased aggrecan deposition, although no differences in other ECM components were observed. Protein analysis of the MSCsec-treated IVD supernatant revealed a significant increase of CXCL1, MCP-1, MIP-3 alpha, IL-6, IL-8 and GRO alpha/beta/gamma (related to TNF, NOD-like receptor and neutrophil chemotaxis signalling), and a decrease of IFN-alpha, IL-10, IL-4, IL-5 and TNF-alpha (associated with T-cell receptor signalling). MSCsec-treated IVD supernatants did not promote angiogenesis and neurogenesis in vitro. Overall, MSCsec can be a safe therapeutic approach, presenting a strong immunomodulatory role in degenerated IVD while potentiating aggrecan deposition, which can open new perspectives on the use of MSCsec as a cell-based/cell-free therapeutic approach to LBP.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 23