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

In vivo repair of full-thickness cartilage defect with human iPSC-derived mesenchymal progenitor cells in a rabbit model.
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在兔模型中用人 iPSC 衍生的间充质祖细胞体内修复全层软骨缺损

DOI:
10.3892/etm.2017.4474
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发表时间:
2017-07
影响因子:
2.7
通讯作者:
Jiang Q
Jiang Q
中科院分区:
医学4区
文献类型:
--
作者:
Xu X;Shi D;Liu Y;Yao Y;Dai J;Xu Z;Chen D;Teng H;Jiang Q

文献摘要

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基于细胞的组织工程具有修复软骨缺损的潜力。诱导多能干细胞(iPSC)被认为是再生医学中的替代细胞来源。本研究的目的是评估来源于人iPSC(hiPSC)的间充质干细胞(MSC)在兔模型中用于软骨缺损再生的用途。在新西兰白色兔的髌骨沟内造成软骨缺损。根据植入情况分为对照组、支架植入组和支架/hiPSCs-MSCs(实验)组。通过胚状体形成步骤从hiPSC产生MSC。流式细胞仪检测后,实验组将hiPSCs-MSCs接种于聚乳酸-羟基乙酸共聚物上,移植于软骨缺损处。在每个时间点处死每组6只家兔。在术后3周和6周,对结局进行了肉眼和组织学评估。在3周和6周时,实验组显示出比对照组和支架植入组更多的软骨缺损填充。在3周时,实验组在软骨缺损中显示出更多的修复组织,尽管没有观察到软骨样组织。6周时,实验组中观察到软骨样组织,而对照组和支架植入组中未观察到。在任何组中均未观察到畸胎瘤形成。结果表明,iPSCs具有修复体内软骨缺损的潜力。因此,诱导多能干细胞有望成为软骨缺损修复的新细胞来源。
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.