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永生化鼠肌腱细胞：肌腱研究的新型创新工具。

Immortalized murine tenocyte cells: a novel and innovative tool for tendon research.

机构信息

Veterinary Tissue Engineering and Regenerative Medicine Lab, Equine Surgery Unit, Department of Companion Animals and Horses, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210, Vienna, Austria.

Institute of Pharmacology and Toxicology, Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210, Vienna, Austria.

出版信息

Sci Rep. 2023 Jan 28;13(1):1566. doi: 10.1038/s41598-023-28318-4.

DOI:10.1038/s41598-023-28318-4
PMID:36709227
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9884217/
Abstract

Primary tenocytes rapidly undergo senescence and a phenotypic drift upon in vitro monolayer culture, which limits tendon research. The Ink4a/Arf locus encodes the proteins p16 and p14 (p19 in mice) that regulate cell cycle progression and senescence. We here established an immortalized cell line using tenocytes isolated from Ink4a/Arf deficient mice (Ink4a/Arf). These cells were investigated at three distinct time points, at low (2-5), intermediate (14-17) and high (35-44) passages. Wild-type cells at low passage (2-5) served as controls. Ink4a/Arf tenocytes at all stages were comparable to wild-type cells regarding morphology, expression of tenogeneic genes (collagen type 1, 3 and 5, Scleraxis, Tenomodulin and Tenascin-C), and surface markers (CD29, CD44 and CD105) and form 3D tendon-like structures. Importantly, Ink4a/Arf tenocytes maintained their phenotypic features and proliferation potential in culture for more than 40 passages and also following freeze-thaw cycles. In contrast, wild-type tenocytes underwent senescence starting in passage 6. These data define Ink4a/Arf tenocytes as novel tool for in vitro tendon research and as valuable in vitro alternative to animal experiments.

摘要

原代肌腱细胞在体外单层培养中会迅速衰老和表型漂移，这限制了肌腱研究。Ink4a/Arf 基因座编码调节细胞周期进程和衰老的蛋白质 p16 和 p14（小鼠中的 p19）。我们在这里使用从 Ink4a/Arf 缺陷型小鼠分离的肌腱细胞建立了永生化细胞系（Ink4a/Arf）。这些细胞在三个不同的时间点进行了研究，即低（2-5）、中（14-17）和高（35-44）传代。低传代（2-5）的野生型细胞作为对照。在所有阶段，Ink4a/Arf 肌腱细胞在形态、肌腱基因（胶原 1、3 和 5、Scleraxis、Tenomodulin 和 Tenascin-C）和表面标志物（CD29、CD44 和 CD105）的表达以及 3D 肌腱样结构的形成方面与野生型细胞相当。重要的是，Ink4a/Arf 肌腱细胞在培养中保持其表型特征和增殖潜力超过 40 代，并且在经历冻融循环后也是如此。相比之下，野生型肌腱细胞从第 6 代开始衰老。这些数据将 Ink4a/Arf 肌腱细胞定义为体外肌腱研究的新工具，并且是动物实验的有价值的体外替代物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ef/9884217/2d1073199841/41598_2023_28318_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ef/9884217/334589f0e658/41598_2023_28318_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ef/9884217/a899e7d31b32/41598_2023_28318_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ef/9884217/d24df67df808/41598_2023_28318_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ef/9884217/3e02fb458e66/41598_2023_28318_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ef/9884217/2d1073199841/41598_2023_28318_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ef/9884217/334589f0e658/41598_2023_28318_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ef/9884217/a899e7d31b32/41598_2023_28318_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ef/9884217/d24df67df808/41598_2023_28318_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ef/9884217/3e02fb458e66/41598_2023_28318_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36ef/9884217/2d1073199841/41598_2023_28318_Fig5_HTML.jpg

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