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首页> 外文期刊>Journal of Cellular Physiology >Long-term in vitro expansion of osteoarthritic human articular chondrocytes do not alter genetic stability: a microsatellite instability analysis.
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Long-term in vitro expansion of osteoarthritic human articular chondrocytes do not alter genetic stability: a microsatellite instability analysis.

机译：长期体外骨关节炎的扩张人体关节软骨细胞不改变基因稳定性:微卫星不稳定性分析。

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摘要

In this study, we investigated genetic damage acquisition during in vitro culture of human osteoarthritic (OA) chondrocytes to evaluate their safety for use in regenerative medicine clinical applications. In particular, we have addressed the impact of long-term in vitro culture on simple sequence repeat stability, to evaluate the involvement of the mismatch repair system (MMR) in the accumulation of genetic damage. MMR, the main post-replicative correction pathway, has a fundamental role in maintaining genomic stability and can be monitored by assessing microsatellite instability (MSI). MMR activity has been reported to decrease with age not only in vivo, but also in vitro in relationship to culture passages. OA chondrocytes from seven donors were cultured corresponding to 13-29 population doublings. Aliquots of the cells were collected and analyzed for MSI at five DNA loci (CD4, VWA, FES, TPOX, and P53) and for MMR gene expression at each subculture. Genetic stability was confirmed throughout the culture period. MMR genes demonstrated a strong coordination at the transcriptional level among the different components; expression levels were very low, in accordance with the observed genetic stability. The reduced expression of MMR genes might underline no need for increasing DNA repair control in the culture conditions tested, in which no genetic damage was evidenced. These data argue for the safety of chondrocytes for cellular therapies and are encouraging for the potential use of in vitro expanded OA chondrocytes, supporting the extension of autologous cell therapy procedures to degenerative articular diseases.
机译：在这项研究中,我们调查了基因损伤收购在体外的人类文化骨关节炎(OA)软骨细胞中评估他们的安全用于再生医学临床应用。解决长期体外的影响文化简单序列重复稳定性评估错配修复的参与系统(MMR)基因的累积损害。通路,在保持基本的作用基因组稳定性和可监控评估微卫星不稳定性(MSI)。活动报道随着年龄增长而减少不仅在体内,而且在体外关系文化的文章。从七个捐助者培养对应13人口倍增。收集和分析在MSI五DNA位点(CD4、协力、菲斯、TPOX和P53)和麻疹在每个亚文化基因表达。稳定了整个文化时期。协调在转录水平不同的组件;很低,根据观察到的基因稳定。可能强调不需要增加DNA修复控制培养条件测试没有证明基因损害。主张软骨细胞细胞的安全治疗和令人鼓舞的潜力使用体外扩大OA软骨细胞,支持扩展自体的细胞退化性关节治疗程序疾病。

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