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软骨组织工程:软骨细胞分化的分子调控以实现合适的软骨基质重建

Cartilage tissue engineering: molecular control of chondrocyte differentiation for proper cartilage matrix reconstruction.

作者信息

Demoor Magali, Ollitrault David, Gomez-Leduc Tangni, Bouyoucef Mouloud, Hervieu Magalie, Fabre Hugo, Lafont Jérôme, Denoix Jean-Marie, Audigié Fabrice, Mallein-Gerin Frédéric, Legendre Florence, Galera Philippe

机构信息

Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT) EA 4652, SFR 146 ICORE, Faculty of Medicine, IBFA, University of Caen/Lower-Normandy (UCLN), France.

Laboratory of Biology and Engineering of Cartilage, UMR 5305 CNRS-Univ. de Lyon, IBCP, Lyon, France.

出版信息

Biochim Biophys Acta. 2014 Aug;1840(8):2414-40. doi: 10.1016/j.bbagen.2014.02.030. Epub 2014 Mar 6.

Abstract

BACKGROUND

Articular cartilage defects are a veritable therapeutic problem because therapeutic options are very scarce. Due to the poor self-regeneration capacity of cartilage, minor cartilage defects often lead to osteoarthritis. Several surgical strategies have been developed to repair damaged cartilage. Autologous chondrocyte implantation (ACI) gives encouraging results, but this cell-based therapy involves a step of chondrocyte expansion in a monolayer, which results in the loss in the differentiated phenotype. Thus, despite improvement in the quality of life for patients, reconstructed cartilage is in fact fibrocartilage. Successful ACI, according to the particular physiology of chondrocytes in vitro, requires active and phenotypically stabilized chondrocytes.

SCOPE OF REVIEW

This review describes the unique physiology of cartilage, with the factors involved in its formation, stabilization and degradation. Then, we focus on some of the most recent advances in cell therapy and tissue engineering that open up interesting perspectives for maintaining or obtaining the chondrogenic character of cells in order to treat cartilage lesions.

MAJOR CONCLUSIONS

Current research involves the use of chondrocytes or progenitor stem cells, associated with "smart" biomaterials and growth factors. Other influential factors, such as cell sources, oxygen pressure and mechanical strain are considered, as are recent developments in gene therapy to control the chondrocyte differentiation/dedifferentiation process.

GENERAL SIGNIFICANCE

This review provides new information on the mechanisms regulating the state of differentiation of chondrocytes and the chondrogenesis of mesenchymal stem cells that will lead to the development of new restorative cell therapy approaches in humans. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.

摘要

背景

关节软骨缺损是一个实实在在的治疗难题,因为治疗选择非常有限。由于软骨的自我再生能力较差,轻微的软骨缺损常常会导致骨关节炎。人们已经开发出多种手术策略来修复受损软骨。自体软骨细胞移植(ACI)取得了令人鼓舞的效果,但这种基于细胞的治疗方法涉及软骨细胞在单层中扩增的步骤,这会导致分化表型的丧失。因此,尽管患者的生活质量有所改善,但重建的软骨实际上是纤维软骨。根据软骨细胞在体外的特殊生理学特性,成功的ACI需要活性且表型稳定的软骨细胞。

综述范围

本综述描述了软骨的独特生理学特性,以及参与其形成、稳定和降解的因素。然后,我们重点关注细胞治疗和组织工程的一些最新进展,这些进展为维持或获得细胞的软骨生成特性以治疗软骨损伤开辟了有趣的前景。

主要结论

当前的研究涉及使用软骨细胞或祖干细胞,结合“智能”生物材料和生长因子。还考虑了其他影响因素,如细胞来源、氧压和机械应变,以及基因治疗在控制软骨细胞分化/去分化过程方面的最新进展。

普遍意义

本综述提供了关于调节软骨细胞分化状态和间充质干细胞软骨生成机制的新信息,这将推动人类新型修复性细胞治疗方法的发展。本文是名为“基质介导的细胞行为和特性”的特刊的一部分。

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