Technology Insight: adult mesenchymal stem cells for osteoarthritis therapy

Abstract

Despite the high prevalence and morbidity of osteoarthritis (OA), an effective treatment for this disease is currently lacking. Restoration of the diseased articular cartilage in patients with OA is, therefore, a challenge of considerable appeal to researchers and clinicians. Techniques that cause multipotent adult mesenchymal stem cells (MSCs) to differentiate into cells of the chondrogenic lineage have led to a variety of experimental strategies to investigate whether MSCs instead of chondrocytes can be used for the regeneration and maintenance of articular cartilage. MSC-based strategies should provide practical advantages for the patient with OA. These strategies include use of MSCs as progenitor cells to engineer cartilage implants that can be used to repair chondral and osteochondral lesions, or as trophic producers of bioactive factors to initiate endogenous regenerative activities in the OA joint. Targeted gene therapy might further enhance these activities of MSCs. Delivery of MSCs might be attained by direct intra-articular injection or by graft of engineered constructs derived from cell-seeded scaffolds; this latter approach could provide a three-dimensional construct with mechanical properties that are congruous with the weight-bearing function of the joint. Promising experimental and clinical data are beginning to emerge in support of the use of MSCs for regenerative applications.

Key Points

  • Osteoarthritis (OA), the most common joint disease, is characterized by degeneration of the articular cartilage that ultimately leads to joint destruction

  • Current treatment strategies for OA are inadequate

  • Delivery of an appropriate mesenchymal stem cell (MSC) population is currently being investigated in the search for new therapies for OA

  • MSCs could be used as trophic producers of bioactive factors to initiate endogenous regenerative activities in the OA joint; their activities might be further enhanced via targeted gene therapy

  • Delivery of MSCs might be achieved either by direct intra-articular injection or by implantation of engineered constructs derived from MSC-seeded scaffolds

  • In the long term, MSC-based technologies could permit the engineering and repair of cartilage as a treatment option for OA joints

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Figure 1: Delivery of MSCs to diseased cartilage in patients with osteoarthritis.
Figure 2: MSCs embedded in a collagen type I hydrogel can be used for tissue engineering of cartilage (U Nöth, unpublished data).
Figure 3: MSCs can be used as vehicles for ex vivo gene delivery.

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Acknowledgements

This work is supported by Deutsche Forschungsgemeinschaft (grant number DFG STE1051/2-1 to AF Steinert and U Nöth), Interdisziplinäres Zentrum für Klinische Forschung (grant number IZKF D-12/1 to U Nöth and D-23/1 to AF Steinert), and the Intramural Research Program of the National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health (grant number Z01 AR 41131 to RS Tuan).

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Correspondence to Rocky S Tuan.

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Nöth, U., Steinert, A. & Tuan, R. Technology Insight: adult mesenchymal stem cells for osteoarthritis therapy. Nat Rev Rheumatol 4, 371–380 (2008). https://doi.org/10.1038/ncprheum0816

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