Summary

Autologous implantation of bone marrow-derived stem cells is a safe procedure with good clinical outcomes obtained at up to 10 years post-operatively.

Abstract

Background

Treatment of articular cartilage defects remains challenging due to the limited capacity of cartilage to repair or regenerate. Autologous implantation of bone marrow-derived stem cells (BMSCs) is a relatively novel procedure that was introduced to overcome some of the limitations of autologous chondrocyte implantation, primarily the limited proliferative capacity of chondrocytes – particularly in older patient cohorts – and the need for two surgical procedures. The longevity of this procedure however has not been established, and there are concerns with regard to the risks of infection and tumour formation particularly with ex-vivo handling and manipulation of cells. We thus performed this study to demonstrate the long-term efficacy and safety of intra-articular autologous BMSC implantation. We hypothesised that intra-articular autologous BMSC implantation would result in good patient-reported outcomes at 10-years post-operatively with no increased risk of adverse events.

Patients and methods
36 patients who had symptomatic focal full-thickness chondral defects in their knee underwent intraarticular implantation of autologous BMSCs and were followed up for 10 years post-operatively. Under local anaesthesia, 30mls of bone marrow aspirate was obtained from the iliac crest of each patient and then expanded in-vitro to a count of between 10 to 15 million cells over a course of 4-5 weeks. In a subsequent surgical procedure, the chondral defect is debrided and covered with a periosteal patch harvested from the proximal tibia or distal femur. Cultured cells are implanted beneath the patch and the patch is secured using fine sutures and tissue glue. Patients subsequently undergo a strict post-operative rehabilitation program and are followed up at defined time periods post-operatively up to 10 years.

The primary outcome measure for this study was the change in patient-reported outcome scores – including the Short Form-36 (SF36) health survey, the International Knee Documentation Committee (IKDC) knee evaluation form, the Lysholm knee score and the Tegner activity scale – from pre-operatively to 10 years post-operatively. As a secondary outcome measure, information was collected on any additional surgical procedures performed to the index knee (as a surrogate marker of treatment efficacy), as well as the development of any infections or tumours. The mixed-effect model (random intercept) was used to determine the effect of time on study outcomes.

Results

The mean age of the cohort at time of surgery was 43.5±11.2 years, with a mean chondral defect size of 4.6±3.5cm2. All of the patient-reported outcomes demonstrated statistically significant improvements after surgery, and with the exception of the mental component summary of the SF-36, remained sustained at 10 years post-operatively. Five patients underwent additional surgical procedures to the same knee – four underwent arthroscopic chondroplasties and one underwent a total knee replacement. None of the patients developed intra-articular infections nor tumours.

Conclusion

Autologous implantation of BMSCs is a safe procedure with good clinical outcomes obtained at up to 10 years post-operatively.