Osteochondral Regeneration with a Scaffold-Free Three-Dimensional Construct of Adipose Tissue-Derived Mesenchymal Stromal Cells in Pigs

Osteochondral lesion is a major joint disease in humans. Therefore, this study was designed to investigate the regeneration of articular cartilage and subchondral bone, using three-dimensional constructs of autologous adipose tissue-derived mesenchymal stromal cells without any biocompatible scaffolds. Mesenchymal stromal cells were harvested by liposuction from seven pigs, isolated enzymatically, and expanded until construct creation. The pig models had two osteochondral defects (cylindrical defects with a diameter of 5.2 mm and a depth of 5 mm) in one of their patello-femoral grooves. A columnar structure consisting of approximately 770 spheroids of 5 × 104 autologous mesenchymal stromal cells were implanted into one of the defects (implanted defect), while the other defect was not implanted (control). The defects were evaluated pathologically at 6 months (in three pigs) and 12 months (in five pigs) after implantation. At 6 months after surgery, histopathology revealed active endochondral ossification underneath the plump fibrocartilage in the implanted defects, but a deficiency of fibrocartilaginous coverage in the controls. At 12 months after surgery, the fibrocartilage was transforming into hyaline cartilage as thick as the surrounding normal cartilage and the subchondral bone was thickening in the implanted defects. The histological averages of the implanted sites were significantly higher than those in the control sites at both 6 and 12 months after surgery. The implantation of a scaffold-free three-dimensional construct of autologous mesenchymal stromal cells into an osteochondral defect can induce regeneration of hyaline cartilage and subchondral bone structures over a period of 12 months.