The second study also applied MSCs in the surgical setting. Vangsness et al randomized 55 patients 7–10 days after partial medial meniscectomy to receive a single intra-articular injection of either placebo or allogeneic MSCs (50 or 150 million) derived from healthy young donors.29 Four of the 17 patients in the lower-cell-dose group showed a >15% increase in meniscal volume relative to baseline compared with zero of 19 in the control arm. Patients in both treatment arms displayed greater decreases in pain scores on a visual analog scale compared with the control group, although the differences were of modest statistical significance.
Larger trials with long-term follow-up will be needed to validate these approaches to augment surgical outcomes and to document the safety, durability and clinical significance of observed effects on structural parameters. Mechanistically, whether injected MSCs actually incorporate into diseased joint structures, such as cartilage, ligaments and menisci, to regenerate healthy functioning tissue remains to be widely demonstrated.
Other approaches to harness stem cell technology for OA treatment may exist. For example, although the vast majority of studies to date have focused on the use of bone marrow-derived MSCs, other sources of stem cells with chondrogenic potential have been identified. These sources include induced pluripotent stem (iPS) cells and endogenous cartilage-derived stem/progenitor cells (CSPCs).30,31
Autologous iPS cells can be generated in vast quantities from tissue isolated via minimally invasive procedures, such as a skin biopsy. Thus, from one iPS preparation, an individual patient could build a therapeutic bank of cells for current and future arthritic conditions.
CSPCs are a recently appreciated population that resides within cartilage and may contribute to tissue homeostasis. Whether the power of these cells could be harvested for OA is unknown, but given their proximity to the diseased tissue, they represent an interesting target.
Lastly, it may be possible to augment MSC activity in situ within an OA joint with small molecules or biologics to bypass the cell isolation, expansion and delivery steps. In a 2012 Science paper, Johnson et al identified a small molecule called kartogenin, which promotes chondrocyte differentiation from MSCs.32 When injected into mouse knees after destabilization surgery, kartogenin reduced the histologic manifestations of OA and decreased joint pain. A subsequent publication incorporated kartogenin into sustained-release nanoparticles and showed similar efficacy in a rat OA model.33 Additional work will be needed to determine the optimal methodology to leverage stem technology for the treatment of OA.