Summary

This study explores creating cartilage treatment for knee osteoarthritis by combining iPS cell-derived cartilage with artificial bone. Cartilage fragments fused with the bone but developed hollow areas over time. Adjusting culture conditions, including spatial constraints, improved tissue formation. These results suggest that modifying culture parameters can enhance the development of osteochondr

Abstract

Objective

Mosaicplasty is one of the effective surgical methods for cartilage injury. However, in cases of osteoarthritis of the knee, due to the extent of the damage, Mosaicplasty is not applicable and osteotomy or total knee arthroplasty has been recommended instead. This study aims to develop a cartilage treatment for osteoarthritis of the knee by creating a composite of iPS cell-derived cartilage tissue and artificial bone, potentially allowing for the creation of an infinitely proliferating osteochondral column tissue.

Methods

Cartilage differentiation was induced in human iPS cells, and cartilage tissue fragments at 3 weeks of differentiation were placed on β-TCP artificial bone (Affinos, Kuraray Co., Ltd.) and co-cultured in cartilage differentiation induction medium. Evaluation items included changes in tissue weight, histological evaluation (HE staining), immunostaining (COL I, COL II), and quantitative assessments of qPCR and GAG levels.

Results

Cartilage tissue fragments derived from iPS cells fused with each other and penetrated the artificial bone. However, hollow formations were observed within the fused cartilage tissue over time. Immunostaining revealed the expression of COL I at the tissue periphery, COL II within the tissue, and also COL II within the artificial bone. qPCR and GAG levels were similar to those of cartilage tissue cultured alone. When spatial restrictions were imposed during hollow formation, the formation of cavities was controlled.

Discussion

While cartilage tissue increased in size when differentiated from human iPS cells and placed on artificial bone, internal hollow formations occurred. Potential causes of hollow formation include deviations due to stirring culture, nutritional deficiencies, and lack of space. Adjusting the space during cultivation was able to suppress cavity formation. These findings suggest that the loading conditions within the joint impact the growth of cartilage tissue.

Conclusion

By adjusting the culture conditions for iPS cell-derived cartilage tissue and artificial bone, it may be possible to create osteochondral column-like tissue.