Combined surgery and chondrocyte cell-sheet transplantation improves clinical and structural outcomes in knee osteoarthritis

Masato Sato,Kosuke Hamahashi,Teruo Okano,Joji Mochida,Yoshihiko Nakamura,Tomonori Takagaki,Miya Ishihara,Ryo Matoba,Masayuki Yamato,Masahiko Watanabe,Genya Mitani,Hiroyuki Kobayashi

doi:10.1038/s41536-019-0069-4

Abstract

Current cartilage regenerative therapies are not fully effective in treating osteoarthritis of the knee (OAK). We have developed chondrocyte sheets for autologous transplantation and tested these in in vitro and in vivo preclinical studies, and have reported that the transplantation of chondrocyte sheets promoted hyaline cartilage repair in rat, rabbit, and minipig models. However, autologous transplantation of chondrocyte sheets has yet to be reported in humans. Here, we report our combination therapy in which conventional surgical treatment for OAK, is followed by autologous chondrocyte sheet transplantation for cartilage repair. Eight patients with OAK and cartilage defects categorized arthroscopically as Outerbridge grade III or IV receive the therapy. Patients are thoroughly assessed by preoperative and postoperative X-rays, magnetic resonance imaging (MRI), arthroscopy, Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Score (LKS), and a laser-induced photoacoustic method to assess cartilage viscoelasticity. Arthroscopic biopsies of all patients are performed 12 months after transplantation for histological evaluation. The properties of the chondrocyte sheets are evaluated using gene expression analysis to investigate the ability to predict the clinical and structural outcomes of the therapy. For this small initial longitudinal series, combination therapy is effective, as assessed by MRI, arthroscopy, viscoelasticity, histology, and the clinical outcomes of KOOS and LKS. Gene marker sets identified in autologous chondrocyte sheets may be predictive of the overall KOOS, LKS, and histological scores after therapy. These predictive gene sets may be potential alternative markers for evaluating OAK treatment.

Highlights

Articular cartilage is a matrix-rich, hypocellular, and vasculaturefree structure that functions as a lubricating and load-bearing surface in the joints
The adaptation of such therapies to cartilaginous defects caused by osteoarthritis of the knee (OAK) might prove difficult because cartilage defects in OAK are variable and changes are associated with female sex, age, and body mass index
OAK-related cartilage defects develop over many years and often require multiple therapies to treat coexisting pathological conditions such as malalignment and ligamentous and meniscal disorders

Summary

INTRODUCTION

Articular cartilage is a matrix-rich, hypocellular, and vasculaturefree structure that functions as a lubricating and load-bearing surface in the joints. Cell-sheet technology has been successfully implemented in clinical research for the regeneration of tissues such as the cornea,[7] myocardium,[8] and esophagus.[9] We were the first to report its applicability in articular cartilage repair with the development of layered chondrocyte sheets.[10,11] We have provided evidence from animal studies indicating the potential of layered chondrocyte sheets in the treatment of a partial defect in rabbit cartilage,[10] and osteochondral defects in rat,[12] rabbit,[13,14] and minipig[15] cartilage These are the types of defects that are usually present in OAK. There were almost no CD31- and CD45-positive cells (Fig. 4g)

RESULTS

DISCUSSION

Adhesions

METHODS

Study design and setting