Advanced cell therapies for articular cartilage regeneration

• Owing to the complexity of cartilage structure and its avascular nature it is difficult to promote its regeneration; advanced therapies are necessary to attain authentic cartilage tissue.
• Large animal studies that relate the quality of cartilaginous tissue to the number of cells administered per cm3 of lesion will be necessary before clinical trial consent.
• Diverse combinations of novel biomaterials, cells, genes, and physical stimuli remain to be assessed as potential strategies for the generation of cartilage tissue.
• It is essential to harmonize the techniques, biomarkers, and outcomes used to characterize the quality of cartilage generated from precursor tissue generated in vitro or in vivo.

Advanced cell-based therapies are promising approaches for stimulating full regeneration of cartilage lesions. In addition to a few commercially available medicinal products, several clinical and preclinical studies are ongoing worldwide. In preclinical settings, high-quality cartilage tissue has been produced using combination strategies involving stem or progenitor cells, biomaterials, and biomolecules to generate a construct for implantation at the lesion site. Cell numbers and mechanical stimulation of the constructs are not commonly considered, but are important parameters to be evaluated in forthcoming clinical studies. We review current clinical and preclinical studies for advanced therapy cartilage regeneration and evaluate the progress of the field.