Identification of WNT16 as a Predictable Biomarker for Accelerated Osteogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells In Vitro
Identification of WNT16 as a Predictable Biomarker for Accelerated Osteogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells In Vitro
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DOI：
10.1155/2019/8503148
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发表时间：
2019-09-10
影响因子：
4.3
通讯作者：
Ryu, Kyung-Ha
中科院分区：
文献类型：
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作者：
Kim, Yu-Hee;Cho, Kyung-Ah;Ryu, Kyung-Ha
应用间充质干细胞（MSCs）治疗骨相关疾病在临床前研究中显示出有希望的结果。然而，分离并定义为MSC的细胞包含异质的祖细胞群。这种异质性可以产生MSC性能的变化，特别是在需要体内分化潜力的应用中，例如骨质疏松症的治疗。在这里，我们的目的是确定扁桃体来源的间充质干细胞（T-MSCs）的遗传标记，可以预测成骨潜力。使用单细胞克隆方法，我们分离并建立了几个非分化（ND）或成骨细胞倾向（OP）克隆系。接下来，我们对保持MSC特征的三个ND和三个OP克隆进行转录组测序，并确定OP克隆中上调的前六个基因。通过实时定量PCR证实了WNT 16和DCLK 1表达的上调，但只有WNT 16表达与来自10个不同供体的T-MSCs的成骨分化相关。总的来说，我们的研究结果表明，WNT 16是一个假定的遗传标记，预测T-MSCs的成骨潜力。因此，在临床应用MSC之前，检查WNT 16表达作为选择标准可以增强干细胞疗法对骨相关并发症（包括骨质疏松症）的治疗功效。
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 in vivo, 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.