Yi Qiao, Liu Ousheng, Yan Fei, Lin Xiao, Diao Shu, Wang Liping, Jin Luyuan, Wang Songlin, Lu Yanqin, Fan Zhipeng
Xiangya Stomatology Hospital, Changsha, China.
Cells Tissues Organs. 2017;203(1):1-11. doi: 10.1159/000448026. Epub 2016 Sep 15.
Dental pulp stem cell (DPSC)-mediated dental pulp regeneration is considered a promising method for the treatment of deep caries with pulpitis. However, mesenchymal stem cell (MSC) senescence is an adverse factor from the perspective of cell-based therapies. In this study, we investigated the characteristics and expression profiles of DPSCs from young and old donors.
DPSCs from young and old donors were cultured in differentiation medium, and their differentiation potentials were assessed. Long noncoding RNA (LncRNA) microarray assays and a bioinformatic analysis were performed to investigate differences in LncRNA and mRNA expression profiles between DPSCs from young and old donors.
We found that DPSCs from young donors exhibited more powerful proliferation ability and greater osteogenic and adipogenic differentiation potentials than DPSCs from old donors. In DPSCs from young donors, numerous LncRNAs were significantly up- (n = 389) or down-regulated (n = 172) compared to DPSCs from old donors. Furthermore, 304 mRNAs were differentially expressed, including 247 up-regulated genes and 57 down-regulated genes in DPSCs from young donors. The bioinformatic analysis identified that several pathways may be associated with DPSC characteristics, such as those involved in the cell cycle and RNA transport, and revealed nuclear transcription factor Y subunit β, general transcription factor IIB, and nuclear receptor subfamily 3 group C member 1 as core regulatory factors and FR249114, FR299091, and ENST00000450004 as core LncRNAs.
Our results indicated that senescence impaired the proliferation and differentiation potentials of DPSCs and that donor age is an important factor that affects their use for tooth regeneration. We also provide insight into the mechanisms responsible for senescence in DPSCs.
牙髓干细胞（DPSC）介导的牙髓再生被认为是治疗伴有牙髓炎的深龋的一种有前景的方法。然而，从基于细胞的治疗角度来看，间充质干细胞（MSC）衰老却是一个不利因素。在本研究中，我们调查了年轻和老年供体来源的DPSC的特征及表达谱。
将年轻和老年供体来源的DPSC在分化培养基中培养，并评估其分化潜能。进行长链非编码RNA（LncRNA）微阵列分析和生物信息学分析，以研究年轻和老年供体来源的DPSC之间LncRNA和mRNA表达谱的差异。
我们发现，与老年供体来源的DPSC相比，年轻供体来源的DPSC表现出更强的增殖能力以及更大的成骨和成脂分化潜能。与老年供体来源的DPSC相比，年轻供体来源的DPSC中有大量LncRNA显著上调（n = 389）或下调（n = 172）。此外，有304个mRNA差异表达，包括年轻供体来源的DPSC中247个上调基因和57个下调基因。生物信息学分析确定，一些途径可能与DPSC特征相关，如参与细胞周期和RNA转运的途径，并揭示了核转录因子Y亚基β、通用转录因子IIB和核受体亚家族3组C成员1作为核心调节因子，以及FR249114、FR299091和ENST00000450004作为核心LncRNA。
我们的结果表明，衰老损害了DPSC的增殖和分化潜能，并且供体年龄是影响其用于牙齿再生的一个重要因素。我们还深入了解了DPSC衰老的机制。
