诱导多能干细胞对骨关节炎软骨损伤的修复作用

发布时间：2018-06-12 17:02

本文选题：骨关节炎 + 诱导多功能干细胞　；参考：《中国组织工程研究》2017年33期

【摘要】：背景:基于干细胞的细胞治疗对于骨关节炎修复有重要的应用前景,其中诱导多能干细胞(induced pluripotent stem cell,i PS细胞)具有较强的增殖和分化潜能,且避免了胚胎干细胞的伦理学问题,目前被认为是细胞治疗中最有前景的种子细胞之一。目的:拟探索一种i PS细胞向软骨细胞分化的有效方法,并研究i PS细胞来源软骨细胞对骨关节炎的修复作用。方法:运用三步法将人i PS细胞诱导分化成软骨样细胞,并检测软骨细胞特异性基因和蛋白的表达。然后将分化后的i PS细胞移植到谷氨酸钠碘乙酸诱导的骨关节炎大鼠模型中。移植实验分为4组:对照组注射生理盐水,造模组注射谷氨酸钠碘乙酸,i PS细胞移植组注射谷氨酸钠碘乙酸后移植i PS细胞,分化后i PS细胞移植组注射谷氨酸钠碘乙酸后移植软骨分化后的i PS细胞。移植15周后micro-CT行断层扫描,并对移植后的关节进行组织学分析。结果与结论:(1)与未分化的i PS细胞相比,经过6 d的拟胚体形成和2周的细胞分化,软骨细胞特异性基因和蛋白(Col2A1,GAG和Sox9)的表达量都明显上升;(2)细胞移植15周后,未观察到免疫反应的发生,micro-CT显示移植细胞后软骨下骨的完整性明显得到改善,组织学分析也表明移植细胞后能产生关节软骨基质。i PS细胞来源软骨细胞的修复效果明显好于i PS细胞;(3)结果表明,i PS细胞来源软骨细胞移植可促进骨关节炎大鼠软骨再生,改善关节功能。
[Abstract]:Background: Stem cell based cell therapy has an important application prospect for osteoarthritis repair, among which induced pluripotent stem cell PS cells have strong proliferation and differentiation potential, and avoid the ethical problems of embryonic stem cells. Currently, it is considered to be one of the most promising seed cells in cell therapy. Aim: to explore an effective method for the differentiation of iPS cells into chondrocytes and to study the repair effect of iPS derived chondrocytes on osteoarthritis. Methods: human I PS cells were induced to differentiate into chondroid cells by three steps method, and the expression of specific genes and proteins in chondrocytes was detected. Then the differentiated iPS cells were transplanted into the rat model of osteoarthritis induced by sodium glutamate iodoacetic acid. The transplantation experiment was divided into four groups: control group was injected with normal saline, model group was injected with sodium glutamate iodoacetic acid and I PS cells were injected with sodium glutamate iodoacetic acid, and I PS cells were transplanted after injection. I PS cells were transplanted into differentiated cartilage after injection of sodium glutamate and iodoacetic acid. Micro-CT scanning was performed 15 weeks after transplantation and histological analysis of the transplanted joints was performed. Results after 6 days of embryoid formation and 2 weeks of cell differentiation, the expression of specific gene and protein of chondrocyte (Col2A1GG and Sox9) in chondrocytes increased significantly 15 weeks after transplantation compared with undifferentiated iPS cells. No immunoreaction was observed. Micro-CT showed that the integrity of subchondral bone was significantly improved after transplantation. Histological analysis also showed that the repair effect of chondrocytes derived from articular cartilage matrix. IPS cells after transplantation was significantly better than that from iPS cells. The results showed that the transplantation of chondrocytes derived from iPS cells could promote cartilage regeneration in osteoarthritis rats. Improve joint function.
【作者单位】：深圳大学医学部深圳抗衰老与再生医学重点实验室;孝感市妇幼保健院脊柱外科;
【基金】：国家自然科学基金(81301597) 深圳新兴战略产业发展专项资金(JCYJ20130326110154156/JCYJ2015052509 2940984/JCYJ20160422090807181)~~
【分类号】：R684.3

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