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RNA Sequencing Analysis of Neotissue Following Combined Autologous Chondrocyte Implantation with High tibial Osteotomy for Femoral Cartilage Injury with Varus Deformity

RNA Sequencing Analysis of Neotissue Following Combined Autologous Chondrocyte Implantation with High tibial Osteotomy for Femoral Cartilage Injury with Varus Deformity

Tomoya Iseki, MD, PhD, JAPAN Ryo Kanto, MD, JAPAN Shintaro Onishi, MD, PhD, JAPAN Yoshitaka Nakao, MD, JAPAN Nobuyoshi Suzuki, MD, JAPAN Takuya Iseki, MD, PhD, JAPAN Shota Morimoto, MD, PhD, JAPAN Hiroshi Nakayama, MD., Ph.D., JAPAN Toshiya Tachibana, MD, PhD, JAPAN

Hyogo Medical University, Nishinomiya, Hyogo, JAPAN


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Summary: RNA sequencing analysis revealed ACI combined with knee osteotomy may be beneficial in promoting the formation of more hyaline-like cartilage repair tissue


Introduction. Autologous chondrocyte implantation (ACI) is a commonly performed procedure to repair local articular defects. However, it is unclear whether neo-tissue following combined ACI with high tibial osteotomy for femoral cartilage injury of a middle-aged patient with varus deformity has the potential to be hyaline-like cartilage. Methods. Four patients with a traumatic cartilage injury with a varus of lower limb leg alignment undergoing combined ACI with open wedge HTO aiming at neutral alignment comprised the study population. The mean age at surgery was 58.3 years. Biopsy was performed for neo-cartilage tissue by a second arthroscopy a year after surgery. Then the histological analysis following Safranin O staining, the cluster analysis of gene expression and the principal component analysis of 3D plots were conducted to evaluate the generation of a more hyaline cartilage phenotype. Results. Neo-tissue stained more strongly for the proteoglycan content (red stain) and the integration at the border of hyaline-like cartilage tissue and subchondral bone without obvious gap was seen. RNA-seq data analysis revealed the cluster of expressed phenotypes in the neo-tissue has a closer enhancement to chondrogenic makers of the chondrocyte cultured from normal humans than the degenerated chondrocyte cultured in an in vitro expansion with IL-1 beta or with BMP, ßGP. Conclusion. This finding suggests that ACI combined with knee osteotomy may be beneficial in promoting the formation of more hyaline-like cartilage repair tissue by the generation of a more hyaline cartilage phenotype even for middle-age OA patients.


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