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永生化人牙胚干细胞的分化和神经保护特性。

Differentiation and neuro-protective properties of immortalized human tooth germ stem cells.

机构信息

Department of Genetics and BioEngineering, College of Engineering and Architecture, Yeditepe University, 26 Ağustos Campus, Kayisdagi cad, Kayisdagi, 34755 Istanbul, Turkey.

出版信息

Neurochem Res. 2011 Dec;36(12):2227-35. doi: 10.1007/s11064-011-0546-7. Epub 2011 Jul 22.

DOI:10.1007/s11064-011-0546-7
PMID:21785835
Abstract

Stem cells are considered to be promising therapeutic options in many neuro-degenerative diseases and injuries to the central nervous system, including brain ischemia and spinal cord trauma. Apart from the gold standard embryonic and mesenchymal origin, human tooth germ stem cells (hTGSCs) have also been shown to enjoy the characteristics of mesenchymal stem cells (MSCs) and the ability to differentiate into adipo-, chondro-, osteo- and neuro-genic cells, suggesting that they might serve as potential alternatives in the cellular therapy of various maladies. Immortalization of stem cells may be useful to avoid senescence of stem cells and to increase their proliferation potential without altering their natural characteristics. This study evaluated the expression of stem cell markers, surface antigens, differentiation capacity, and karyotype of hTGSCs that have been immortalized by human telomerase reverse transcriptase (hTERT) or simian vacuolating virus 40 (SV40) large T antigen. These undying cells were also evaluated for their neuro-protective potential using an in vitro SH-SY5Y neuro-blastoma model treated with hydrogen-peroxide or doxo-rubicin. Although hTGSC-SV40 showed abnormal karyotypes, our results suggest that hTGSC-hTERT preserve their MSC characteristics, differentiation capacity and normal karyotype, and they also possess high proliferation rate and neuro-protective effects even at great passage numbers. These peculiars indicate that hTGSC-hTERT could be used as a viable model for studying adipo-, osteo-, odonto- and neuro-genesis, as well as neuro-protection of MSCs, which may serve as a springboard for potentially utilizing dental waste material in cellular therapy.

摘要

干细胞被认为是许多神经退行性疾病和中枢神经系统损伤(包括脑缺血和脊髓创伤)的有前途的治疗选择。除了胚胎和间充质来源的金标准外,人牙胚干细胞(hTGSCs)也表现出间充质干细胞(MSCs)的特征,并能够分化为脂肪、软骨、骨和神经生成细胞,这表明它们可能作为各种疾病的细胞治疗的潜在替代物。干细胞的永生化可能有助于避免干细胞衰老,并增加其增殖潜力,而不改变其天然特征。本研究评估了永生化的 hTGSCs 表达干细胞标志物、表面抗原、分化能力和染色体核型,这些 hTGSCs 通过人端粒酶逆转录酶(hTERT)或猿猴空泡病毒 40(SV40)大 T 抗原永生化。这些不朽细胞还通过体外 SH-SY5Y 神经母细胞瘤模型用过氧化氢或阿霉素处理来评估其神经保护潜力。尽管 hTGSC-SV40 显示出异常的染色体核型,但我们的结果表明 hTGSC-hTERT 保留了它们的 MSC 特征、分化能力和正常染色体核型,并且即使在较高的传代数下,它们也具有较高的增殖率和神经保护作用。这些特点表明 hTGSC-hTERT 可作为研究脂肪、骨、牙和神经发生以及 MSC 的神经保护作用的可行模型,这可能为利用牙齿废料进行细胞治疗提供一个起点。

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本文引用的文献

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Curr Neurovasc Res. 2010 Feb;7(1):49-58. doi: 10.2174/156720210790820181.
2
Stem cell transplantation for neurometabolic and neurodegenerative diseases.干细胞移植治疗神经代谢和神经退行性疾病。
Neuropharmacology. 2010 May;58(6):845-54. doi: 10.1016/j.neuropharm.2009.12.015. Epub 2009 Dec 28.
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Potential role of dental stem cells in the cellular therapy of cerebral ischemia.牙髓干细胞在脑缺血细胞治疗中的潜在作用。
通过调节和表达水平实现脂肪来源间充质干细胞(MSC)永生化
J Pers Med. 2023 Nov 20;13(11):1621. doi: 10.3390/jpm13111621.
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The other side of the coin: mesenchymal stromal cell immortalization beyond evasion of senescence.硬币的另一面:超越衰老逃逸的间质基质细胞永生化。
Hum Cell. 2023 Sep;36(5):1593-1603. doi: 10.1007/s13577-023-00925-3. Epub 2023 Jun 21.
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