METHODS: Osteoarthritis was induced at the right knee of sheep by complete resection of ACL and medial meniscus. Stem cells from sheep were induced to chondrogenic lineage. Test sheep received 5 mls single doses of 2 × 107 autologous PKH26-labelled ADSCs or BMSCs, while controls received basal medium. Functional recovery of the knees was evaluated via electromyography.
RESULTS: Induced ADSCs had 625, 255, 393, 908, 409, 157 and 1062 folds increases of collagen I, collagen II, aggrecan, SOX9, cartilage oligomeric protein, chondroadherin and fibromodullin compare to uninduced cells, while BMSCs had 702, 657, 321, 276, 337, 233 and 1163 respectively; p = .001. Immunocytochemistry was positive for these chondrogenic markers. 12 months post-treatment, controls scored 4 in most regions using ICRS, while the treated had 8; P = .001. Regenerated cartilages were positive to PKH26 and demonstrated the presence of condensing cartilages on haematoxylin and eosin; and Safranin O. OA degenerations caused significant amplitude shift from right to left hind limb. After treatments, controls persisted with significant decreases; while treated samples regained balance.
CONCLUSIONS: Both ADSCs and BMSCs had increased chondrogenic gene expressions using TGF-β3 and BMP-6. The treated knees had improved cartilage scores; PKH26 can provide elongated tracking, while EMG results revealed improved joint recoveries. These could be suitable therapies for osteoarthritis.
METHODS: Literature search was performed to identify all level I and II studies reporting the clinical and structural outcome of any ACI generation in human knees using the following medical electronic databases: PubMed, EMBASE, Cochrane Library, CINAHL, SPORTDiscus and NICE healthcare database. The level of evidence, sample size calculation and risk of bias were determined for all included studies to enable quality assessment.
RESULTS: Twenty studies were included in the analysis, reporting on a total of 1094 patients. Of the 20 studies, 13 compared ACI with other treatment modalities, seven compared different ACI cell delivery methods, and one compared different cell source for implantation. Studies included were heterogeneous in baseline design, preventing meta-analysis. Data showed a trend towards similar outcomes when comparing ACI generations with other repair techniques and when comparing different cell delivery methods and cell source selection. Majority of the studies (80 %) were level II evidence, and overall the quality of studies can be rated as average to low, with the absence of power analysis in 65 % studies.
CONCLUSION: At present, there are insufficient data to conclude any superiority of ACI techniques. Considering its two-stage operation and cost, it may be appropriate to reserve ACI for patients with larger defects or those who have had inadequate response to other repair procedures until hard evidence enables specific clinical recommendations be made.
LEVEL OF EVIDENCE: II.
METHODS: The proximal tibia was resected as a single osteochondral unit during total knee replacement from patients (N = 10). The osteoarthritic chondrocytes were isolated from the osteochondral units, and characterized using reverse transcriptase-polymerase chain reaction. The isolated osteoarthritic chondrocytes were cultured and embedded in agarose, and then subjected to 10% and 20% uniaxial dynamic compression up to 8-days using a bioreactor. The morphological features and changes in the osteoarthritic chondrocytes upon compression were evaluated using scanning electron microscopy. Safranin O was used to detect the presence of cartilage matrix proteoglycan expression while quantitative analysis was conducted by measuring type VI collagen using an immunohistochemistry and fluorescence intensity assay.
FINDINGS: Gene expression analysis indicated that the isolated osteoarthritic chondrocytes expressed chondrocyte-specific markers, including BGN, CD90 and HSPG-2. Moreover, the compressed osteoarthritic chondrocytes showed a more intense and broader deposition of proteoglycan and type VI collagen than control. The expression of type VI collagen was directly proportional to the duration of compression in which 8-days compression was significantly higher than 4-days compression. The 20% compression showed significantly higher intensity compared to 10% compression in 4- and 8-days.
INTERPRETATION: The biosynthetic activity of human chondrocytes from osteoarthritic joints can be enhanced using selected compression regimes.