Although this approach can be effective, it has some drawbacks.24 First, it is usually reserved for younger patients with discrete cartilage lesions. Patients with more diffuse chondral lesions, as seen in OA, are mostly excluded. Second, the recovery period is lengthy to allow for tissue regeneration. Finally, two surgical procedures are required, which carry cost and safety concerns.
More recently, investigators have turned toward the use of mesenchymal stem cells (MSCs) for the treatment of OA.24,25 MSCs are multipotent and, under the proper growth conditions, can differentiate into all stromal lineages, including osteoblasts, chondrocytes, adipocytes, fibroblasts and myocytes. These cells are found in higher numbers in bone marrow, adipose tissue, amniotic fluid and umbilical cord blood. MSCs generally exhibit immunosuppressive properties, expressing cytokine and cell surface molecules that suppress immune and inflammatory responses.26,27 The theory behind the application of MSCs to OA is clear: What better treatment for a disease characterized by inflammation and tissue degeneration is there than one that may simultaneously reduce the former and reverse the latter?
Many variables need to be taken into account when considering the use of MSCs for OA. These variables include:
- The source of the MSCs with respect to the harvest site (e.g., bone marrow vs. adipose tissue) and donor (i.e., autologous vs. allogeneic);
- Isolation and expansion protocols;
- Delivery methods (i.e., intra-articular injection vs. surgical implantation);
- The number of cells to inject;
- Whether growth factors to drive chondrogenic differentiation should be co-administered; and
- How to control batch to batch variation to bring a therapy from the experimental setting to clinical practice.
In addition, the appropriate outcome measures are not clear. Obviously, one would like to see improvements in pain and function, but will the therapy need to regrow cartilage to be considered successful?
Lastly, although often considered immune privileged, allogeneic MSCs may induce adaptive immune responses, according to recent studies.26,27 For a chronic disease, such as OA, in which repeated therapeutic procedures are likely to be necessary, allogeneic responses against the injected MSCs could limit applications in individual patients.
In contrast to the lack of studies for enzyme inhibitors and lubricative therapies, numerous studies have tested MSCs in OA patients.25 Most of these are case series lacking control groups, but two recent trials bear review.
The first isolated autologous bone marrow MSCs from an iliac crest aspirate at the time patients underwent tibial osteotomy and microfracture for medial compartmental OA.28 These cells were expanded and injected approximately three weeks later in autologous serum. Control patients received cell-free serum, but none of the patients was blinded to treatment allocation. Small, but statistically significant, improvements were observed for multiple clinical outcome measures. Most interesting, 19 of 28 patients who received MSCs had a >50% improvement in filling of cartilage defects by MRI compared with only four of 28 patients in the control arm. Although the widespread applicability of this approach is unclear, the study lends credence to the possibility that MSCs promote cartilage repair.