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用于软骨组织工程的间充质干细胞分化:三维环境与机械负荷的个体及协同效应

Differentiation of mesenchymal stem cells for cartilage tissue engineering: Individual and synergetic effects of three-dimensional environment and mechanical loading.

作者信息

Panadero J A, Lanceros-Mendez S, Ribelles J L Gomez

机构信息

Center/Departament of Physics, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal; Center for Biomaterials and Tissue Engineering, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia, Spain.

Center/Departament of Physics, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal; BCMaterials, Parque Científico y Tecnológico de Bizkaia, 48160-Derio, Spain.

出版信息

Acta Biomater. 2016 Mar;33:1-12. doi: 10.1016/j.actbio.2016.01.037. Epub 2016 Jan 27.

DOI:10.1016/j.actbio.2016.01.037
PMID:26826532
Abstract

UNLABELLED

Chondrogenesis of dedifferentiated chondrocytes and mesenchymal stem cells is influenced not only by soluble molecules like growth factors, but also by the cell environment itself. The latter is achieved through both mechanical cues - which act as stimulation factor and influences nutrient transport - and adhesion to extracellular matrix cues - which determine cell shape. Although the effects of soluble molecules and cell environment have been intensively addressed, few observations and conclusions about the interaction between the two have been achieved. In this work, we review the state of the art on the single effects between mechanical and biochemical cues, as well as on the combination of the two. Furthermore, we provide a discussion on the techniques currently used to determine the mechanical properties of materials and tissues generated in vitro, their limitations and the future research needs to properly address the identified problems.

STATEMENT OF SIGNIFICANCE

The importance of biomechanical cues in chondrogenesis is well known. This paper reviews the existing literature on the effect of mechanical stimulation on chondrogenic differentiation of mesenchymal stem cells in order to regenerate hyaline cartilage. Contradictory results found with respect to the effect of different modes of external loading can be explained by the different properties of the scaffolding system that holds the cells, which determine cell adhesion and morphology and spatial distribution of cells, as well as the stress transmission to the cells. Thus, this review seeks to provide an insight into the interplay between external loading program and scaffold properties during chondrogenic differentiation. The review of the literature reveals an important gap in the knowledge in this field and encourages new experimental studies. The main issue is that in each of the few cases in which the interplay is investigated, just two groups of scaffolds are compared, leaving intermediate adhesion conditions out of study. The authors propose broader studies implementing new high-throughput techniques for mechanical characterization of tissue engineering constructs and the inclusion of fatigue analysis as support methodology to more exhaustive mechanical characterization.

摘要

未标记

去分化软骨细胞和间充质干细胞的软骨形成不仅受生长因子等可溶性分子的影响,还受细胞环境本身的影响。后者通过机械信号(其作为刺激因子并影响营养物质运输)和与细胞外基质信号的粘附(其决定细胞形状)来实现。尽管可溶性分子和细胞环境的影响已得到深入研究,但关于两者之间相互作用的观察和结论却很少。在这项工作中,我们综述了关于机械和生化信号的单一作用以及两者结合的最新研究状况。此外,我们讨论了目前用于确定体外生成的材料和组织的力学性能的技术、它们的局限性以及为妥善解决已发现问题所需的未来研究方向。

意义声明

生物力学信号在软骨形成中的重要性是众所周知的。本文综述了关于机械刺激对间充质干细胞软骨分化以再生透明软骨影响的现有文献。关于不同外部加载模式的影响所发现的相互矛盾的结果,可以通过支撑细胞的支架系统的不同特性来解释,该特性决定细胞粘附、细胞形态和空间分布以及向细胞的应力传递。因此,本综述旨在深入了解软骨分化过程中外部加载程序与支架特性之间的相互作用。对文献的综述揭示了该领域知识的一个重要空白,并鼓励开展新的实验研究。主要问题在于,在少数研究这种相互作用的案例中,每次仅比较两组支架,而忽略了中间的粘附条件。作者建议开展更广泛的研究,采用新的高通量技术对组织工程构建体进行力学表征,并纳入疲劳分析作为更详尽力学表征的支持方法。

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