Mesenchymal chondroprogenitor cell origin and therapeutic potential

Osteoarthritis (OA) is a chronic disease of the joints characterized by progressive destruction of articular cartilage resulting in painful, limited joint movement. In the European Union over 39 million people exhibit symptoms of OA, a number anticipated to double in the next decade, creating an imperative for the timely development of effective treatments for the disease [1]. Current clinical therapies such as pharmaceutical interventions, bone marrow stimulation techniques or microfracture do not result in regeneration of healthy cartilage tissue [2,3], but focus on the short-term relief of OA symptoms. When pharmaceutical intervention fails, clinicians regularly revert to invasive and permanent solutions.The first widely accepted regenerative treatment for cartilage repair was autologous chondrocyte transplantation. Despite its initial therapeutic promise, chondrocyte transplantation has associated complications, such as donor site morbidity, repair cell de-differentiation with expansion in vitro and restricted cellular life span upon implantation [4]. Immature progenitor cells with the potential to develop into mature tissues in response to appropriate cues have therefore become a primary focus of cartilage repair strategies as an alternative to chondrocyte-based methods [5].The application of chondroprogenitors, cells that are specifically pre-disposed to differentiate into mature chondrocytes, to repair articular lesions and subsequently inhibit the onset of OA is a current focus of research efforts. As the mature articular joint develops from embryonic mesodermal precursors that differentiate into chondroprogenitors and ultimately into mature adult chondrocytes or synoviocytes, it is hypothesized that progenitors retained in these adult articular tissues provide a potential reservoir of chondroprogenitors.The development of the embryonic appendicular skeleton, whereby undifferentiated limb mesenchyme matures into a cartilaginous precursor and subsequently int