Purpose. The present study aims to evaluate the long-term results of a single-stage cell-based procedure for symptomatic focal cartilage defects in the knee and to compare them with that of the mid-term evaluation. It was hypothesized that the good outcomes of culture-expanded adipose derived mesenchymal stem cells (AD-MSCs) implantation reported in previous series would not deteriorate with time.

Methods. Thirty consecutive patients underwent cartilage repair in the knee with adipose-derived culture-expanded mesenchymal stem cells were prospectively followed for 6 years. To assess functional outcomes patients-reported tools were used including two validated subjective knee questionnaires, the Injury & Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC) score, the Tegner activity scale and the visual analogue scale (VAS) for pain. Clinical evaluation was quantified by the IKDC examination form. Radiological evaluation of the repair tissue was performed using the MOCART score.

Results. All scores recorded a statistically significant improvement (p <0.05) at the final follow-up compared with baseline. The KOOS evaluation showed increased scores in all subcategories. More precisely, KOOS-pain was improved from 62.6 (range 44.0-70.1) to 95.5 (range 92.0-100.0), KOOS-Symptoms from 60.9 (range 46.3-68.0) to96.0 (range 89.0-96.0), KOOS-ADL 60.0 (range 46.8-74.6) to 92.0 (range 87.8-97.0) KOOS-Sports/Rec from 32.5 (range 20.0-45.0) to 70.0 (range 55.0-85.0) and KOOS-QOL from 34.4 (range 23.5-51.5) to 84.5 (range 73.5-88.0). The average IKDC score increased from to 40.2 (range 33.9-49.7) to 76.6 (range 68.4-84.7). Sport activity evaluated using Tegner Activity Score as well as VAS for pain demonstrated the same tendency of significant improvement. MRI findings confirmed complete filling of the defect and integration to the border zone for 68% of the patients. Three patients underwent postoperative biopsies and the histological analysis demonstrated the presence of hyaline-like tissue.

Conclusions. Adipose-Derived culture-expanded mesenchymal stem cells were shown to be an efficient and safe single-stage cell-based procedure for symptomatic, full-thickness knee chondral lesions. The findings of the present study demonstrate that all patients presented significant long-term clinical, functional and radiological improvement.

Keywords: chondral lesion, adipose derived stem cells, cartilage repair, regenerative medicine, tissue engineering, scaffolds, cell culture expansion