The synovium has remarkable self-renewal ability and self-regenerates in patients with inflammatory arthritis undergoing synovectomy. In addition, during osteoarthritis the joint demonstrates apparent repair mechanisms that can result in aberrant formation of cartilage and bone in the form of chondro-osteophytes. Altogether, this presumes existence of endogenous stem cells in the joint.
More than a decade ago, we isolated from the adult human synovium mesenchymal stem cells (MSCs) with multipotency inherent at the single cell level (De Bari et al., Arthritis Rheum 2001). In a comparative study of MSCs from multiple tissue sources including bone marrow, the synovial MSCs displayed superiority in cartilage formation (Sakaguchi et al., Arthritis Rheum 2005), pointing to synovial MSCs as possible ideal chondroprogenitors for articular cartilage repair.
We have postulated that postnatally the synovium may function as a reservoir of stem cells for the regeneration / repair of joint tissues such as articular cartilage and menisci that are known to have poor intrinsic regeneration potential. In this regard, the synovium shares with the joint surface a common embryonic derivation from the developmental joint interzone (Koyama et al., 2008; Rountree et al., 2004), while bone marrow and periosteum which, like synovium, contain MSCs in adult life, appear to have distinct developmental origins.
In adult life, stem cells are considered as quiescent slow-cycling cells which, following injury, become activated and undergo proliferation and differentiation into mature cell type(s) in order to safeguard tissue anatomy and function. On the basis of this notion, we recently provided data on the identification and characterization of endogenous resident MSCs in the adult mouse knee joint synovium in vivo. We used a double nucleoside labelling scheme in a mouse model of knee joint surface injury (Eltawil et al., Osteoarthritis Cartilage 2009) and identified in the adult knee synovium long-term label-retaining slow-cycling cells that, following injury to the articular cartilage, proliferated and differentiated into chondrocytes, hence displaying typical features of adult stem cells (Kurth et al., Arthritis Rheum 2011). These slow-cycling cells were non-haematopoietic, non-endothelial stromal cells with a phenotype compatible with MSCs, and were located in the lining layer and in perivascular areas. Notably, these cells were distinct from pericytes.
The existence of functional MSC niches in the adult joint opens up unprecedented opportunities for pharmacological interventions by using medications that would target MSC niches and related reparative signalling pathways to activate and modulate intrinsic joint tissue regeneration and, in a broader picture, to influence outcomes of joint disorders and restore joint homeostasis.
Disclosure of Interest None Declared
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