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关节内注射诱导成软骨的骨髓干细胞延缓羊骨关节炎模型进展的潜力。

The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model.

机构信息

Tissue Engineering Centre, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.

出版信息

Exp Gerontol. 2012 Jun;47(6):458-64. doi: 10.1016/j.exger.2012.03.018. Epub 2012 Apr 10.

DOI:10.1016/j.exger.2012.03.018
PMID:22759409
Abstract

In recent years, the use of bone marrow mesenchymal stem cell (BMSC) implantation has provided an alternative treatment for osteoarthritis. The objective of this study is to determine whether or not an intra-articular injection of a single dose of autologous chondrogenic induced BMSC could retard the progressive destruction of cartilage in a surgically induced osteoarthritis in sheep. Sheep BMSCs were isolated and divided into two groups. One group was cultured in chondrogenic media containing (Ham's F12:DMEM, 1:1) FD+1% FBS+5 ng/ml TGFβ3+50 ng/ml IGF-1 (CM), and the other group was cultured in the basal media, FD+10% FBS (BM). The procedure for surgically induced osteoarthritis was performed on the donor sheep 6 weeks prior to intra-articular injection into the knee joint of a single dose of BMSC from either group, suspended in 5 ml FD at density of 2 million cells/ml. The control groups were injected with basal media, without cells. Six weeks after injection, gross evidence of retardation of cartilage destruction was seen in the osteoarthritic knee joints treated with CM as well as BM. No significant ICRS (International Cartilage Repair Society) scoring was detected between the two groups with cells. However macroscopically, meniscus repair was observed in the knee joint treated with CM. Severe osteoarthritis and meniscal injury was observed in the control group. Interestingly, histologically the CM group demonstrated good cartilage histoarchitecture, thickness and quality, comparable to normal knee joint cartilage. As a conclusion, intra-articular injection of a single dose of BMSC either chondrogenically induced or not, could retard the progression of osteoarthritis (OA) in a sheep model, but the induced cells indicated better results especially in meniscus regeneration.

摘要

近年来,骨髓间充质干细胞(BMSC)植入已为骨关节炎提供了一种替代治疗方法。本研究旨在确定单次关节内注射自体诱导成软骨的 BMSC 是否能延缓绵羊手术诱导的骨关节炎中软骨的进行性破坏。分离绵羊 BMSCs 并分为两组。一组在含有(Ham's F12:DMEM,1:1)FD+1%FBS+5ng/ml TGFβ3+50ng/ml IGF-1(CM)的软骨形成培养基中培养,另一组在基础培养基 FD+10%FBS(BM)中培养。在关节内注射 BMSC 前 6 周,对供体绵羊进行手术诱导骨关节炎,将来自任一培养组的 BMSC 以 200 万细胞/ml 的密度悬浮在 5ml FD 中,进行单次关节内注射。对照组注射基础培养基,不注射细胞。注射后 6 周,在接受 CM 和 BM 处理的骨关节炎膝关节中,肉眼可见软骨破坏的延迟迹象。但两组细胞的 ICRS(国际软骨修复协会)评分无显著差异。然而,在 CM 处理的膝关节中,肉眼可见半月板修复。对照组观察到严重的骨关节炎和半月板损伤。有趣的是,组织学上 CM 组表现出良好的软骨组织形态学、厚度和质量,与正常膝关节软骨相当。总之,单次关节内注射经诱导或未经诱导的 BMSC 均可延缓绵羊模型中骨关节炎(OA)的进展,但诱导细胞的再生效果更好,尤其是半月板再生。

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