Mesenchymal Stem Cell Extracellular Vesicles as Adjuvant to Bone Marrow Stimulation in Chondral Defect Repair in a Minipig Model.

OBJECTIVE: This study evaluated the effects of mesenchymal stem cell-extracellular vesicles (MSC-EVs) on chondrocyte proliferation in vitro and on cartilage repair in vivo following bone marrow stimulation (BMS) of focal chondral defects of the knee. METHODS: Six adult Göttingen minipigs received 2 chondral defects in each knee. The pigs were randomized to treatment with either BMS combined with MSC-EVs or BMS combined with phosphate-buffered saline (PBS). Intraarticular injections MSC-EVs or PBS were performed immediately after closure of the surgical incisions, and at 2 and 4 weeks postoperatively. Repair was evaluated after 6 months with gross examination, histology, histomorphometry, immunohistochemistry, and micro-computed tomography (µCT) analysis of the trabecular bone beneath the defect. RESULTS: Defects treated with MSC-EVs had more bone in the cartilage defect area than the PBS-treated defects (7.9% vs. 1.5%, P = 0.02). Less than 1% of the repair tissue in both groups was hyaline cartilage. International Cartilage and Joint Preservation Society II histological scoring showed that defects treated with MSC-EVs scored lower on "matrix staining" (20.8 vs. 50.0, P = 0.03), "cell morphology" (35.4 vs. 53.8, P = 0.04), and "overall assessment" (30.8 vs. 52.9, P = 0.03). Consistently, defects treated with MSC-EVs had lower collagen II and higher collagen I areal deposition. Defects treated with MSC-EVs had subchondral bone with significantly higher tissue mineral densities than PBS-treated defects (860 mg HA/cm3 vs. 838 mg HA/cm3, P = 0.02). CONCLUSION: Intraarticular injections of MSC-EVs in conjunction with BMS led to osseous ingrowth that impaired optimal cartilage repair, while enhancing subchondral bone healing.

Demographics in Patients Receiving Matrix-Assisted Chondrocyte Implantation (MACI) in the Ankle.

Objective. To compare demographics and cartilage lesion characteristics of patients enrolled in clinical trials investigating autologous chondrocyte implantation (ACI) in the ankle joint with those actually scheduled for matrix-assisted chondrocyte implantation (MACI) using database records. Design. Anonymized data from patients scheduled for MACI treatment in the ankle in Australia/Asia and Europe were obtained from the Genzyme/Sanofi database. Average age, defect size, and male-female ratio were analyzed and compared by country. A literature search was performed on PubMed and Google Scholar and clinical cohort studies and prospective comparative trials using ACI and related treatments in the ankle joint were identified. Weighted average age, weighted defect size, and male-female ratio were analyzed and compared with database data. Results. The 167 patients included from the databases from Europe and Australia had a mean age of 33.4 years (range 14-64 years) and a mean defect size of 2.27 cm2 (range 0.25-16 cm2). Male-female ratio was 4:3. Patients from European countries were significantly younger and had significantly larger defects compared with patients from Australia. From the literature search a total of 472 patients were included from 28 studies. The mean age was 32.2 years (range 15-62 years). Male-female ratio was 3:2. Weighted mean size was 1.94cm2 (range 0.3-16). There were no significant differences between previous studies and databases. Conclusion. No differences in sizes and age were found between patients enrolled in clinical trials and patients scheduled for MACI outside clinical trials. The sizes of treated defects followed the general recommendations. There were, however, significant differences between countries.