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鉴定WNT16作为扁桃体来源间充质干细胞加速成骨分化的可预测生物标志物

Identification of WNT16 as a Predictable Biomarker for Accelerated Osteogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells .

作者信息

Kim Yu-Hee, Cho Kyung-Ah, Lee Hyun-Ji, Park Minhwa, Kim Han Su, Park Joo-Won, Woo So-Youn, Ryu Kyung-Ha

机构信息

Department of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea.

Department of Otolaryngology, College of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea.

出版信息

Stem Cells Int. 2019 Sep 10;2019:8503148. doi: 10.1155/2019/8503148. eCollection 2019.

Abstract

The application of mesenchymal stem cells (MSCs) for treating bone-related diseases shows promising outcomes in preclinical studies. However, cells that are isolated and defined as MSCs comprise a heterogeneous population of progenitors. This heterogeneity can produce variations in the performance of MSCs, especially in applications that require differentiation potential , such as the treatment of osteoporosis. Here, we aimed to identify genetic markers in tonsil-derived MSCs (T-MSCs) that can predict osteogenic potential. Using a single-cell cloning method, we isolated and established several lines of nondifferentiating (ND) or osteoblast-prone (OP) clones. Next, we performed transcriptome sequencing of three ND and three OP clones that maintained the characteristics of MSCs and determined the top six genes that were upregulated in OP clones. Upregulation of WNT16 and DCLK1 expression was confirmed by real-time quantitative PCR, but only WNT16 expression was correlated with the osteogenic differentiation of T-MSCs from 10 different donors. Collectively, our findings suggest that WNT16 is a putative genetic marker that predicts the osteogenic potential of T-MSCs. Thus, examination of WNT16 expression as a selection criterion prior to the clinical application of MSCs may enhance the therapeutic efficacy of stem cell therapy for bone-related complications, including osteoporosis.

摘要

间充质干细胞(MSCs)在治疗骨相关疾病中的应用在临床前研究中显示出了有前景的结果。然而,分离并定义为MSCs的细胞包含一群异质性的祖细胞。这种异质性会导致MSCs性能的差异,尤其是在需要分化潜能的应用中,比如骨质疏松症的治疗。在此,我们旨在鉴定扁桃体来源的MSCs(T-MSCs)中能够预测成骨潜能的遗传标志物。我们使用单细胞克隆方法,分离并建立了几株未分化(ND)或易于分化为成骨细胞(OP)的克隆株。接下来,我们对三株保持MSCs特征的ND克隆株和三株OP克隆株进行了转录组测序,并确定了在OP克隆株中上调的前六个基因。通过实时定量PCR证实了WNT16和DCLK1表达上调,但只有WNT16的表达与来自10个不同供体的T-MSCs的成骨分化相关。总体而言,我们的研究结果表明WNT16是预测T-MSCs成骨潜能的一个假定遗传标志物。因此,在MSCs临床应用前将检测WNT16表达作为一种选择标准,可能会提高干细胞疗法对包括骨质疏松症在内的骨相关并发症的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d385/6754949/dca602cd9717/SCI2019-8503148.001.jpg

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