Mesenchymal stromal cells and rheumatic disorders

Mesenchymal stromal cells (MSC), often incorrectly called stem cells, have been the intense focus of in vitro studies and animal models of rheumatic and other diseases over more than a decade. Despite multiple plausible mechanisms of action and a plethora of positive in vivo animal studies, few randomised controlled clinical trials have demonstrated meaningful clinical benefit in any condition so far. This could be due to confusion in cell product terminology, complexity of clinical study design and execution or agreement on meaningful outcome measures. It could also indicate that MSC as currently employed are ineffective. Within the rheumatic diseases, SLE, rheumatoid arthritis (RA) and osteoarthritis (OA) have received most attention. Uncontrolled multiple trial data from over 300 SLE patients have been published from one centre suggesting a positive outcome; one single centre comparative study in 172 RA was positive and no human studies have compared intra-articular MSC therapy to non-MSC techniques for osteoarthritis in the absence of surgery. Two randomised studies suggested benefit from the addition of bone marrow derived MSC and peripheral blood mononuclear cells added to surgical "standard of care" in knee OA and knee focal cartilage defects, respectively. The possible reasons for this apparent mismatch between expectation and clinical reality will be discussed.