Embryonic Stem Cells Form Articular Cartilage, not Teratomas, in Osteochondral Defects of Rat Joints

Abstract

Embryonic stem (ES) cells are considered to be a potential tool for repairing articular cartilage defects, but so far it has been impossible to cause these cells to differentiate into chondrocytes exclusively, either in vivo or in vitro. To explore a potential new cell source of cell transplantation for articular cartilage defects, we transplanted ES cells into articular cartilage defects in immunosuppressed rats. ES cells (AB2.2 or CCE cells) were transplanted into articular cartilage defects in the patellar groove of immunosuppressed rats treated with cyclosporine. The cells were histologically observed until 8 weeks after transplantation. To determine whether the repair tissue in the defect in the AB2.2-transplanted group was derived from the transplanted cells, the neomycin-resistant gene, which had been transfected into AB2.2 cells but does not exist in rat cells, was used for detection. The cells produced cartilage, resulting in repair of the defects from 4 weeks until 8 weeks after the transplantation without forming any teratomas. The neomycin-resistant gene was detected in every sample, demonstrating that the repair tissue in the AB2.2-transplanted group was derived from the transplanted AB2.2 cells. The environment of osteochondral defects is chondrogenic for ES cells. ES cells may thus be a potential tool for repairing articular cartilage defects.

Bone and cartilage repair by transplantation of induced pluripotent stem cells in murine joint defect model

“…ES and iPS cells do not face the problem of deterioration during cell passaging. Tanigami and collaborators had reported that they were successful in regenerating rat knee joint cartilage by transplanting undifferentiated mouse ES cells embedded in collagen gel into the knee joint defect model, and just by letting the rats freely mobilize their knees (25). This study suggested that undifferentiated ES cells could be differentiated and organized into proper tissues just by being placed in a physiological environment.…”

Lessons from musculoskeletal stem cell research: The key to successful regenerative medicine development

“…Currently, much of the emphasis, which is backed by considerable investment, is being placed on the controlled differentiation of ESCs along given cell lineages, including cartilage and bone (21)(22)(23). However, in the case of cartilage repair, which is a key target for regenerative medicine, several cell-based repair strategies already exist, including implantation of cultureexpanded articular chondrocytes, implantation of culture-expanded MSCs, and bone microfracture techniques, among other strategies (14,24,25).…”

Chondrogenic Progenitor Cells and Articular Cartilage Repair

“…Wakitani et al [71] transplanted ESCs into articular cartilage defects in immunosuppressed rats, with the ESCs producing cartilage which resulted in repair of the defects at 8 weeks after the transplantation without formation of any teratomas. Hwang et al [72] treated rat osteochondral defects with chondrogenically committed human ESC derived MSCs.…”