Chasing Chimeras - The elusive stable chondrogenic phenotype

The choice of the best-suited cell population for the regeneration of damaged or diseased cartilage depends on the effectiveness of culture conditions (e.g. media supplements, three-dimensional scaffolds, mechanical stimulation, oxygen tension, co-culture systems) to induce stable chondrogenic phenotype. Herein, advances and shortfalls in in vitro, preclinical and clinical setting of various in vitro microenvironment modulators on maintaining chondrocyte phenotype or directing stem cells towards chondrogenic lineage are critically discussed. Chondrocytes possess low isolation efficiency, limited proliferative potential and rapid phenotypic drift in culture. Mesenchymal stem cells are relatively readily available, possess high proliferation potential, exhibit great chondrogenic differentiation capacity, but they tend to acquire a hypertrophic phenotype when exposed to chondrogenic stimuli. Embryonic and induced pluripotent stem cells, despite their promising in vitro and preclinical data, are still under-investigated. Although a stable chondrogenic phenotype remains elusive, recent advances in in vitro microenvironment modulators are likely to develop clinically- and commercially-relevant therapies in the years to come.