Pattappa, G; Peroglio, M; Sakai, D; Mochida, J; Benneker, Lorin Michael; Alini, M; Grad, S (2014). CCL5/RANTES is a key chemoattractant released by degenerative intervertebral discs in organ culture. European cells & materials eCM, 27, pp. 124-136. University of Wales
|
Text
v027a10.pdf - Published Version Available under License Publisher holds Copyright. Download (1MB) | Preview |
Release of chemotactic factors in response to tissue damage has been described for different musculoskeletal tissues, including the intervertebral disc (IVD). This study investigated the chemoattractants that are released by induced degenerative IVDs and may be involved in recruiting mesenchymal stem cells (MSCs). Bovine caudal discs were cultured within a bioreactor and loaded under conditions that mimicked physiological or degenerative settings. Between days 4-6, medium was replaced by PBS, which was subsequently used for proteomic, ELISA and immunoprecipitation analyses of secreted chemokines and cytokines. A Boyden chamber assay was used to observe human MSC migration towards native and chemokine depleted media. Gene expression levels of chemokine receptors in human MSCs were analysed, and CCL5 was localised in bovine and human IVD by immunohistochemistry. Proteomic analysis revealed the presence of CCL5 and CXCL6 within conditioned media. Higher concentrations of CCL5 were found in the degenerative media, and a relationship was found between interleukin-1β and CCL5 concentration. Chemokine immunoprecipitation showed that MSCs had a significantly reduced chemotactic migration towards CCL5-immunoprecipitated and CCL5/CXCL6 co-immunoprecipitated media, whilst CXCL6 depletion did not change MSC chemotaxis. MSCs showed a significant increase in mRNA expression of the CCL5 receptors, CCR1 and CCR4, upon culture in degenerative media. Furthermore, CCL5 was identified in bovine and human disc tissue by immunohistochemistry. Hence, CCL5 may be a key chemoattractant that is produced and released by the intervertebral disc cells. Therefore, these factors could be used to enhance stem/progenitor cell mobilisation in regenerative therapies for early stages of disc degeneration.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery |
UniBE Contributor: |
Benneker, Lorin Michael |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1473-2262 |
Publisher: |
University of Wales |
Language: |
English |
Submitter: |
Stefanie Zurbuchen |
Date Deposited: |
12 Feb 2015 09:53 |
Last Modified: |
05 Dec 2022 14:40 |
PubMed ID: |
24500793 |
BORIS DOI: |
10.7892/boris.62964 |
URI: |
https://boris.unibe.ch/id/eprint/62964 |
Actions (login required)
 |
Edit item |