Abstract
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.
Highlights
Osteochondral lesion, defined as cartilage degradation and subchondral bone sclerosis/deformity, is a major joint disease that typically develops into Osteoarthritis, and the associated disability can decrease quality of life in humans [1]
A strong shift in mean fluorescence intensity (MFI) on flow cytometry was detected with antibodies against CD90 and CD105 (Fig. 3A and B), while no signals were detected with antibodies against CD34 and CD45 (Fig. 3C and D)
adipose tissue (AT)-mesenchymal stem cells (MSCs) contracted to form colonies and showed a hyaline cartilagelike structure that was positively stained with alcian blue (Fig. 4B)
Summary
Osteochondral lesion, defined as cartilage degradation and subchondral bone sclerosis/deformity, is a major joint disease that typically develops into Osteoarthritis, and the associated disability can decrease quality of life in humans [1]. The implantation of artificial bone and autologous chondrocytes seeded into a collagen scaffold has shown favorable restoration of Tissue Eng Regen Med (2018) 15(1):101113 bone and cartilage [4, 5]. The collagen scaffold remaining in the implanted sites for long periods can prevent the regeneration of hyaline cartilage, but can promote its replacement to fibrous cartilage [8]. Based on these theories, it is possible that artificial scaffold can be unfavorable in order to regenerate articular cartilage; investigation of cartilage regeneration by using scaffold-free construct of cells is necessary. Many concerns remain that need to be solved, including immunogenicity [9, 10], longterm safety of scaffold degradation products [11], and risk of infection or transmission of disease
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