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用于修复兔模型中严重慢性骨软骨缺损的细胞磁靶向系统

Cell Magnetic Targeting System for Repair of Severe Chronic Osteochondral Defect in a Rabbit Model.

作者信息

Mahmoud Elhussein Elbadry, Kamei Goki, Harada Yohei, Shimizu Ryo, Kamei Naosuke, Adachi Nobuo, Misk Nabil Ahmed, Ochi Mitsuo

机构信息

Department of Orthopaedic Surgery, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

出版信息

Cell Transplant. 2016;25(6):1073-83. doi: 10.3727/096368915X689613. Epub 2015 Sep 28.

Abstract

The aim of this study was to investigate a cell delivery system for repair of severe chronic osteochondral defects using magnetically labeled mesenchymal stem cells (m-MSCs), with the aid of an external magnetic device, through the accumulation of a small number of m-MSCs into a desired area and to detect the suitable number of autologous m-MSCs needed for repair of the defect. Twenty-six male Japanese white rabbits aged 6 months were used. An osteochondral defect was created bilaterally at the weight-bearing surface of the medial femoral condyle of the rabbits' knees (3 mm diameter; 4 mm depth). At 4 weeks after creation of the defect, autogenic transplantation of the m-MSCs into the defect area was performed, followed by 10-min exposure to an external magnetic device, where animals were divided into four groups: high (1 × 10(6) m-MSCs), medium (2 × 10(5) m-MSCs), low (4 × 10(4) m-MSCs), and control (PBS injection). At 4 and 12 weeks posttransplantation of m-MSCs, repaired tissue was assessed histologically using the Fortier score with toluidine blue staining. Transplantation of a low number of m-MSCs was not enough to improve osteogenesis and chondrogenesis, but the medium and high groups improved repair of the chronic defect with chondrogenic tissues and showed histologically significantly better results than the control and low groups. The use of a magnetic targeting system for delivering m-MSCs has the potential to overcome the clinical hurdles for repair of the severe chronic osteochondral defect. Furthermore, this system is predicted to produce good clinical outcomes for humans, not only to repair osteochondral defects but also to repair a variety of damaged tissues.

摘要

本研究的目的是研究一种细胞递送系统,该系统利用磁性标记的间充质干细胞(m-MSCs)修复严重的慢性骨软骨缺损,借助外部磁性装置,通过将少量m-MSCs聚集到所需区域,并检测修复缺损所需的合适数量的自体m-MSCs。使用了26只6个月大的雄性日本白兔。在兔膝关节内侧股骨髁的负重表面双侧制造骨软骨缺损(直径3毫米;深度4毫米)。在缺损形成后4周,将m-MSCs自体移植到缺损区域,然后暴露于外部磁性装置10分钟,将动物分为四组:高剂量组(1×10⁶ m-MSCs)、中剂量组(2×10⁵ m-MSCs)、低剂量组(4×10⁴ m-MSCs)和对照组(注射PBS)。在m-MSCs移植后4周和12周,使用Fortier评分和甲苯胺蓝染色对修复组织进行组织学评估。低数量m-MSCs的移植不足以改善成骨和软骨形成,但中剂量组和高剂量组改善了慢性缺损的软骨组织修复,并且在组织学上显示出比对照组和低剂量组明显更好的结果。使用磁性靶向系统递送m-MSCs有可能克服修复严重慢性骨软骨缺损的临床障碍。此外,预计该系统对人类能产生良好的临床结果,不仅能修复骨软骨缺损,还能修复各种受损组织。

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