Functional articular cartilage repair: here, near, or is the best approach not yet clear?

• Published in: Nature reviews. Rheumatology Vol. 9; no. 5; pp. 277 - 290
• Main Authors: Mastbergen, Simon C., Saris, Daniël B. F., Lafeber, Floris P. J. G.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2013; Nature Publishing Group
• Subjects: 692/699/1670/407; 692/700/565/545/488; Animals; Antirheumatic Agents - therapeutic use; Arthritis; Biomarkers; Boundary conditions; Care and treatment; Cartilage; Cartilage, Articular - injuries; Cartilage, Articular - physiology; Cell- and Tissue-Based Therapy; Disease; Homeostasis; Humans; Integrated approach; Joint Diseases - therapy; Joint surgery; Medicine; Medicine & Public Health; Orthopedic Procedures; Orthopedics; Osteoarthritis; Regenerative medicine; review-article; Rheumatology; Netherlands
• ISSN: 1759-4790; 1759-4804
• DOI: 10.1038/nrrheum.2013.29

Nestled at the interface of rheumatology—which tackles biochemical modulation of joint homeostasis—and orthopaedics, with its focus on mechanical joint homeostasis, is the burgeoning field of cartilage tissue structure-modifying therapies. Besides halting damage, though, is actual repair of cartilage clinically possible? This Review is a comprehensive guide to the extensive developmental progress, both made and that remains to come, in regenerative medicine for degenerative joint disease.
In this Review we describe three approaches for cartilage tissue repair at the rheumatology–orthopaedics interface: disease-modifying osteoarthritis (OA) drug (DMOAD) treatment; cell-based therapies, and intrinsic cartilage repair by joint distraction. DMOADs can slow the progression of joint damage. Cell-based therapies have evolved to do the same, through selection of the most potent cell types (and combinations thereof), as well as identification of permissive boundary conditions for indications. Joint distraction techniques, meanwhile, have now demonstrated the capacity to stimulate actual intrinsic tissue repair. Although this progress is promising, true biological joint reconstruction remains distant on the developmental pathway of 'regenerative medicine'. Prolonged functional repair—that is, cure of diseases such as OA—remains an unmet medical need and scientific challenge, for which comparative and constructive interaction between these physical, chemical and cellular approaches will be required. Careful selections of patients and combinations of approaches will need to be made and tested to demonstrate their cost-effectiveness. Only with such rational and integrated assessment of outcomes will the promising results of these approaches be consolidated in clinical practice.
Key Points
The quest for disease-modifying osteoarthritis drugs (DMOADs) is becoming increasingly fruitful; modalities that alter bone turnover—and, indirectly, cartilage damage—seem to be most effective
Long-term outcomes of cell-based therapies are good; quality has improved with European advanced therapeutic medicinal products regulation; the current goal is combining cartilage components, mesenchymal stem cells and trophic factors into a one-stage therapy
Joint distraction can induce tissue-structure modification in degenerated knee joints, accompanied by prolonged symptomatic improvement that supports the concept of cartilage repair translating into real clinical benefit
Joint distraction itself might represent an integrated approach to tackling the separate chondroprotective, chondroreparative and bone turnover-modifying mechanisms targeted by DMOADs and cell-based therapies
Combining DMOAD and cell-based therapies with joint distraction might be a worthwhile approach towards functional tissue repair, as distraction provides a temporary biomechanical joint homeostasis that facilities repair mechanisms