In vivo repair of full-thickness cartilage defect with human iPSC-derived mesenchymal progenitor cells in a rabbit model

使用人类 iPSC 衍生的间充质祖细胞在兔模型中修复全层软骨缺损

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作者:Xingquan Xu, Dongquan Shi, Yubao Liu, Yao Yao, Jin Dai, Zhihong Xu, Dongyang Chen, Huajian Teng, Qing Jiang

Abstract

Cell-based tissue engineering has the potential to restore cartilage defects. Induced pluripotent stem cells (iPSCs) are regarded as an alternative cell source in regenerative medicine. The purpose of the present study was to evaluate the use of mesenchymal stem cells (MSCs) derived from human iPSCs (hiPSCs) for the regeneration of cartilage defects in a rabbit model. Cartilage defects were made in the patellar grooves of New Zealand white rabbits. The rabbits were then divided into three groups according to implantation: Control group, scaffold implantation group and scaffold/hiPSCs-MSCs (experimental) group. MSCs were generated from hiPSCs via a step of embryoid body formation. Following flow cytological analysis, the hiPSCs-MSCs were plated onto poly(lactic-co-glycolide) and then transplanted into the cartilage defects in the experimental group. Six rabbits from each group were sacrificed at each time point. The outcome was assessed macroscopically and histologically at 3 and 6 weeks post-surgery. At 3 and 6 weeks, the experimental group showed more cartilage defect filling compared with the control and scaffold implantation groups. At 3 weeks, the experimental group showed much more repair tissue in the cartilage defect, although no cartilage-like tissue was observed. At 6 weeks, cartilage-like tissue was observed in the experimental group but not in the control or scaffold implantation groups. No teratoma formation was observed in any of the groups. The results indicate that iPSCs have the potential to repair cartilage defects in vivo. Therefore, iPSCs could be a new cell source for cartilage defect repair.

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