Repair of cartilage defects in osteoarthritis rats with induced pluripotent stem cell derived chondrocytes.

Yanxia Zhu,Kedong Song,Xiaomin Wu,Yuhong Liang,Xuenong Zou,Guangqian Zhou,Hongsheng Gu

doi:10.1186/s12896-016-0306-5

Abstract

BackgroundThe incapacity of articular cartilage (AC) for self-repair after damage ultimately leads to the development of osteoarthritis. Stem cell-based therapy has been proposed for the treatment of osteoarthritis (OA) and induced pluripotent stem cells (iPSCs) are becoming a promising stem cell source.ResultsThree steps were developed to differentiate human iPSCs into chondrocytes which were transplanted into rat OA models induced by monosodium iodoacetate (MIA). After 6 days embryonic body (EB) formation and 2 weeks differentiation, the gene and protein expression of Col2A1, GAG and Sox9 has significantly increased compare to undifferentiated hiPSCs. After 15 weeks transplantation, no immune responses were observed, micro-CT showed gradual engraftment and the improvement of subchondrol plate integrity, and histological examinations demonstrated articular cartilage matrix production.ConclusionshiPSC could be an efficient and clinically translatable approach for cartilage tissue regeneration in OA cartilages.

Highlights

The incapacity of articular cartilage (AC) for self-repair after damage leads to the development of osteoarthritis
We developed an efficient, simple and reproducible system to differentiate induced pluripotent stem cell (iPSC) into chondrocytes, the total process from iPSC to chondrocyte is just 2 to 3 weeks
After iPS cell transplantation, we found some areas of the articular cartilage were still intact, the thickness of the subchondral plate became thinner compared with monosodium iodoacetate (MIA)-injected knee, iPS derived chondrocytes transplanted articular cartilage have thicker subchondral bone compare with that of iPSCs transplantation

Summary

Introduction

The incapacity of articular cartilage (AC) for self-repair after damage leads to the development of osteoarthritis. Stem cell-based therapy has been proposed for the treatment of osteoarthritis (OA) and induced pluripotent stem cells (iPSCs) are becoming a promising stem cell source. The increasing prevalence of degenerative cartilage diseases, osteoarthritis (OA), presents an important social and healthcare problem. OA is mediated by several pathogenic mechanisms, including enzymatic degradation of extracellular matrix, deficient new matrix formation, cell death, and abnormal activation and hypertrophic differentiation of cartilage cells [2]. Methods for regenerating chondrocytes and cartilage tissue are expected to substitute or supplement conventional therapies for such diseases. In this respect, the use of stem cells in combination with

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