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年龄对人肌腱细胞样细胞的细胞生物学特性和刺激潜能的影响。

Influence of age on the cell biological characteristics and the stimulation potential of male human tenocyte-like cells.

机构信息

Julius Wolff Institute, Center for Musculoskeletal Surgery, Charité-Universitaetsmedizin Berlin, Berlin, Germany.

出版信息

Eur Cell Mater. 2012 Jul 12;24:74-89. doi: 10.22203/ecm.v024a06.

Abstract

The incidence of rotator cuff tears and recurrent defects positively correlate with patient age. However, this observation has never been analysed at the cellular level. The present study aims to better understand this correlation by investigating cellular characteristics of rotator cuff tenocytes of different age groups. Additionally, previous studies reported on stimulating effects of Bone Morphogenetic Protein (BMP) -2 and BMP-7 on tenocytes. Thus, the second aim was to investigate, whether the stimulation potential of tenocytes demonstrates age-related differences. Tenocyte-like cells from supraspinatus tendons of young and aged patients were analysed for the following cell biological characteristics: cell density, cell growth, marker expression, collagen-I protein synthesis, stem cell phenotype, potential for multipotent differentiation and self-renewal. To analyse the stimulation potential, cells were treated with BMP-2 and BMP-7 in 2D-/3D-cultures. Measured parameters included cell activity, marker expression and collagen-I protein synthesis. An effect of age was seen for cell growth and stem cell potential but not on extracellular matrix level. Cells from both groups responded to BMP-7 by increasing cell activity, collagen-I expression and protein synthesis. BMP-2 led to smaller increases in these parameters when compared to BMP-7. In general, 3D-cultivation improved the stimulation compared to 2D-culture. The cell biological characteristics of tenocyte-like cells, considered important for successful restoration of the tendon-bone unit, were inferior in elderly donors. This may help explain higher rates of recurrent defects seen in elderly patients. Regarding the stimulation potential, on a cellular level young and aged patients may benefit from biological augmentation with BMPs.

摘要

肩袖撕裂和复发性缺损的发生率与患者年龄呈正相关。然而,这一观察结果从未在细胞水平上进行过分析。本研究旨在通过研究不同年龄组肩袖肌腱细胞的细胞特征,更好地理解这种相关性。此外,先前的研究报告了骨形态发生蛋白(BMP)-2 和 BMP-7 对肌腱细胞的刺激作用。因此,第二个目的是研究肌腱细胞的刺激潜能是否存在与年龄相关的差异。对来自年轻和老年患者的肩袖肌腱的肌腱细胞样细胞进行了以下细胞生物学特征分析:细胞密度、细胞生长、标志物表达、I 型胶原蛋白合成、干细胞表型、多能分化潜能和自我更新潜能。为了分析刺激潜能,将细胞在 2D-/3D 培养中用 BMP-2 和 BMP-7 处理。测量的参数包括细胞活性、标志物表达和 I 型胶原蛋白合成。细胞生长和干细胞潜能存在年龄效应,但细胞外基质水平没有年龄效应。两组细胞对 BMP-7 的反应是通过增加细胞活性、I 型胶原表达和蛋白合成来实现的。与 BMP-7 相比,BMP-2 导致这些参数的增加较小。一般来说,3D 培养比 2D 培养更能提高刺激效果。肌腱细胞样细胞的细胞生物学特征被认为对成功恢复肌腱-骨单位很重要,在老年供体中较差。这可能有助于解释在老年患者中更常见的复发性缺损。关于刺激潜能,在细胞水平上,年轻和老年患者可能受益于 BMP 的生物增强。

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