eCM (Eur Cell Mater / e Cells & Materials) eCM Open Access Scientific Journal
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2018   Volume No 36 – pages 218-230

Title: Mesenchymal stem cell secretome reduces pain and prevents cartilage damage in a murine osteoarthritis model

Authors: S Khatab, GJVM van Osch, N Kops, YM Bastiaansen-Jenniskens, PK Bos, JAN Verhaar, MR Bernsen, GM van Buul

Address: Department of Orthopaedics and Otorhinolaryngology, Erasmus MC, University Medical Centre, Wytemaweg 80, 3015 CN Rotterdam, the Netherlands.

E-mail: g.vanosch at

Abstract: Mesenchymal stem cells (MSCs) represent a promising biological therapeutic option as an osteoarthritis (OA)-modifying treatment. MSCs secrete factors that can counteract inflammatory and catabolic processes and attract endogenous repair cells. The effects of intra-articular injection of MSC secretome on OA-related pain, cartilage damage, subchondral bone alterations and synovial inflammation were studied in a mouse collagenase-induced OA model. The MSC secretome was generated by stimulating human bone-marrow-derived MSCs with interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα). 54 mice were randomly assigned to injections with i) MSC secretome from 20,000 MSCs, ii) 20,000 MSCs or iii) medium (control). Pain was assessed by hind limb weight distribution. Cartilage damage, subchondral bone volume and synovial inflammation were evaluated by histology. MSC-secretome- and MSC-injected mice showed pain reduction at day 7 when compared to control mice. Cartilage damage was more abundant in the control group as compared to healthy knees, a difference which was not found in knees treated with MSC secretome or MSCs. No effects were observed regarding synovial inflammation, subchondral bone volume or the presence of different macrophage subtypes. Injection of MSC secretome, similarly to injection of MSCs, resulted in early pain reduction and had a protective effect on the development of cartilage damage in a murine OA model. By using the regenerative capacities of the MSC-secreted factors, it will be possible to greatly enhance the standardisation, affordability and clinical translatability of the approach. This way, this biological therapy could evolve towards a true disease-modifying anti-osteoarthritic drug.

Key Words: Mesenchymal stem cell, secretome, osteoarthritis, animal model, pain, synovial inflammation, cartilage damage.

Publication date: November 06th 2018

Article download: Pages 218-230 (PDF file)

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