Osteochondral Regeneration of the Loading-bearing Site Using a Scaffold Free Three-dimensional Construct of Adipose Tissue-derived Mesenchymal Stem Cells in Pigs

Background: Many surgical strategies for reconstruction of both bone and cartilage have ever been investigated to restore joint structure and function in the late stages of Osteoarthritis (OA). This study was designed to investigate the regeneration of articular cartilage and subchondral bone in the loading-bearing site using a three-dimensional (3D) construct of autologous adipose tissue-derived mesenchymal stem cells (AT-MSCs). Methods: A 3D construct consisting of approximately 1,920 spheroids each containing 5.0 × 104 AT-MSCs was implanted into an osteochondral defect (with a diameter of 6.8 mm and a depth of 6 mm) in the right femoral medial condyle in five adult mini-pigs. The contralateral (left femoral) defect was the control. At three and six months post-operatively, the defects were evaluated using both CT and MR imaging. The radiolucent volume (RV, mm3) of the defects was calculated based on the multiplanar reconstruction of the CT images. MR images and gross and histologic pathology features were scored using a modified-MOCART system and the ICRS system, respectively, at six months post-operatively. Results: The percentages of RVs at three and six months compared with those immediately after the surgeries were significantly decreased in the implanted defects compared with the control defects. The total scores of modified- MOCART system were also significantly increased in the implanted sites comparing to the controls. Although there were no statistical differences in the average of gross scores, the average histological scores were significantly higher in the implanted sites than in the control sites. Conclusion: This is the first report suggesting that implantation of a scaffold-free three dimensional construct of only AT-MSCs into the osteochondral defect regenerates the original cartilage and subchondral bone structures over six months post-operatively in the loading-bearing site of large animal.