Cell therapy for repair of cartilage defects in the ankle - how does it work and who should we treat?

Untreated cartilage defects in the ankle can lead to osteoarthritis (OA). Various versions of a cell therapy, using a one-step arthroscopic technique to deliver bone-marrow aspirate concentrate (BMAC) into a cartilage defect to delay the development of OA have been used in the ankle at RJAH. Previously used to treat cartilage defects in the knee1, one such technique called Complete Cartilage Repair (CCR) has been used at RJAH for the treatment of cartilage defects in the ankle (n=62)2. Preliminary data from our laboratory using such patients BMAC samples have demonstrated that not all cells adhere to a traditional mesenchymal stem cell (MSC) phenotype, thus questioning the suggested mechanism of action. This reverse-translational study aims to establish the exact cell population/s obtained via BMAC (in both commercially available normal and patient samples); we aim to assess their chondrogenic potency and phenotype and how these cells might relate to a good clinical outcome. Furthermore, we will aim to identify biomarkers within the synovial fluid and bloods which may predict which patients are most likely to benefit from this treatment.

Commercially-available bone marrow aspirate from young, healthy donors will be concentrated via centrifugation using the three BMAC preparation kits trialled clinically in our centre (Complete Cartilage Repair (CCR), RegenGlobal; Heragen® Maxx, Heraeus; and Angel® BMC, Arthrex). Flow cytometry and qRT-PCR will be used to characterise the cell phenotype/s and assess their chondrogenic potency. Additionally, how BMAC cells respond to the environment within the scaffold used in the CCR kit is unknown. Therefore, cells will be seeded within this scaffold in the laboratory and their viability and chondrogenic potency assessed by live/dead assays and qRT-PCR, respectively. Synovial fluid and bloods will be collected from patients at the time of BMAC (CCR) implantation and a panel of protein markers, found to predict clinical outcome following knee surgery3-5, will be assessed to identify proteins that may predict clinical outcome following treatment. At 6 and 12 months post-treatment, clinical outcome and general well-being of the patients enrolled in this study will be assessed using a validated foot and ankle questionnaire (MOXFQ) and the EQ5D questionnaire, respectively.

The comparison of the three different preparation kits will indicate which preparation yields the most suitable cell type/s for cartilage repair. This will provide clinically relevant information which could contribute to a clinical trial application and for seeking more substantive scientific funding.