Selecting the right OA patient endotype for MSC therapies
OA, inflammation, synovial inflammation, pain, heterogeneous disease
INFLAMMATION
OA is a heterogeneous disease, and at least six clinical phenotype subsets have been identified [Categorizing OA patients with the inflammatory phenotype (based on synovial inflammation) may be most relevant to MSC therapies with their proposed anti-inflammatory mechanisms of action. Indeed, the current most effective therapeutic treatments for OA symptoms and pain are nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular corticosteroid injections that work through anti-inflammatory effects on synovial inflammation with large effect sizes [Part of the conundrum is that it is not clear that an inflammatory phenotype is a true OA clinical phenotype [US imaging has been postulated to be one such measurement modality for identifying patients with increased inflammation [Ultimately, the use of combinatorial tools, including US and MRI, serum biomarkers, and synovial fluid levels of immune cell subsets and proinflammatory mediators, will help identify true inflammatory patient endotypes (vs. clinical phenotypes) that might be most receptive to MSC treatments based on their proposed anti-inflammatory and immunomodulatory effects, particularly on host MΦs. Flow cytometry evaluations would thus be valuable to profile cellular responses within local joint biopsy samples, including immune cell profiling of synovial fluid as we have previously shown [The identification of circulating miR biomarkers [