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用于关节软骨修复的间充质干细胞-胶原微球:细胞密度与分化状态

Mesenchymal stem cell-collagen microspheres for articular cartilage repair: cell density and differentiation status.

作者信息

Li Y Y, Cheng H W, Cheung K M C, Chan D, Chan B P

机构信息

Tissue Engineering Laboratory, Department of Mechanical Engineering, Room 711, Haking Wong Building, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region.

Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.

出版信息

Acta Biomater. 2014 May;10(5):1919-29. doi: 10.1016/j.actbio.2014.01.002. Epub 2014 Jan 10.

DOI:10.1016/j.actbio.2014.01.002
PMID:24418436
Abstract

Mesenchymal stem cells (MSC) hold promise for cartilage repair. A microencapsulation technique was previously established to entrap MSC in collagen microspheres, and the collagen fibrous meshwork was found to be an excellent scaffold for supporting MSC survival, growth and differentiation. This study investigates the importance of cell density and differentiation status of MSC-collagen microspheres in cartilage repair. MSC were isolated from rabbit bone marrow and encapsulated in collagen microspheres. The effects of pre-differentiating the encapsulated MSC into chondrogenic lineages and different cell densities on cartilage repair were investigated in rabbits. Implantation of undifferentiated collagen-MSC microspheres formed hyaline-like cartilage rich in type II collagen and glycosaminoglycans (GAG) at 1month post-implantation. By 6months, hyaline cartilage rich in type II collagen and GAG, but negative for type I collagen, and partial zonal organization were found in both undifferentiated and chondrogenically differentiated groups in the high cell density group. The undifferentiated group and high cell density group significantly improved the O'Driscoll histological score. Moreover, the undifferentiated group significantly increased the GAG content. The mechanically differentiated group showed stiffer but thinner cartilage, while the undifferentiated group showed thicker but softer cartilage compared with their respective contra-lateral controls. This work suggests that a higher local cell density favors cartilage regeneration, regardless of the differentiation status of MSC, while the differentiation status of MSC does significantly affect regeneration outcomes.

摘要

间充质干细胞(MSC)在软骨修复方面具有应用前景。此前已建立一种微囊化技术,将MSC包裹在胶原微球中,发现胶原纤维网络是支持MSC存活、生长和分化的优良支架。本研究探讨了MSC - 胶原微球的细胞密度和分化状态在软骨修复中的重要性。从兔骨髓中分离出MSC并包裹在胶原微球中。研究了将包裹的MSC预分化为软骨生成谱系以及不同细胞密度对兔软骨修复的影响。植入未分化的胶原 - MSC微球后1个月,形成了富含II型胶原和糖胺聚糖(GAG)的透明样软骨。到6个月时,高细胞密度组的未分化组和软骨生成分化组均发现富含II型胶原和GAG但I型胶原呈阴性的透明软骨以及部分带状组织。未分化组和高细胞密度组显著提高了奥德里斯科尔组织学评分。此外,未分化组显著增加了GAG含量。与各自的对侧对照相比,机械分化组显示软骨更硬但更薄,而未分化组显示软骨更厚但更软。这项工作表明,较高的局部细胞密度有利于软骨再生,而与MSC的分化状态无关,不过MSC的分化状态确实会显著影响再生结果。

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