l -肉碱通过端粒依赖途径降低骨髓常驻C-Kit+造血祖细胞的细胞衰老。

IF 2.1 4区 医学 Q4 CELL & TISSUE ENGINEERING Current stem cell research & therapy Pub Date : 2023-01-01 DOI:10.2174/1574888X17666220511141123
Ezzatollah Fathi, Soheila Montazersaheb, Zohreh Sanaat, Ailar Nakhlband, Somayeh Vandghanooni, Raheleh Farahzadi, Ilja Vietor
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引用次数: 0

摘要

背景:氧气水平升高可引起线粒体DNA损伤和染色体畸变,导致干细胞分化缺陷,最终导致干细胞衰老。近年来,一些研究报道了抗氧化剂可以改善干细胞的存活,并随后影响这些细胞的效力和分化。在再生医学的细胞治疗中,寻找能够降低干细胞在扩增过程中衰老倾向的因子具有很大的潜力。本研究旨在通过检测l -肉碱(LC)对C-kit+造血祖细胞(HPCs)部分信号通路组分表达的影响,探讨LC对造血祖细胞(HPCs)衰老的影响。方法:为此,采用磁活化细胞分选(MACS)方法富集骨髓常驻C-kit+ HPCs,并采用流式细胞术和免疫细胞化学对其进行表征。细胞用LC处理,在处理结束时,对细胞进行real - time PCR技术和western blotting实验,分别测量端粒长度和评估蛋白质表达。结果:0.2 mM LC使端粒长度延长,TERT蛋白表达增加。此外,作为端粒依赖途径的关键组分,p38、p53、BCL2和p16的蛋白表达显著增加。结论:LC可以通过这些信号通路组分增加端粒长度,是提高C-kit+ HPCs细胞存活和维持的有效因素。
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L-Carnitine Reduced Cellular Aging of Bone Marrow Resident C-Kit+ Hematopoietic Progenitor Cells Through Telomere Dependent Pathways.

Background: Increased oxygen species levels can induce mitochondrial DNA damage and chromosomal aberrations and cause defective stem cell differentiation, leading finally to senescence of stem cells. In recent years, several studies have reported that antioxidants can improve stem cell survival and subsequently affect the potency and differentiation of these cells. Finding factors, which reduce the senescence tendency of stem cells upon expansion, has great potential for cellular therapy in regenerative medicine. This study aimed to evaluate the effects of L-carnitine (LC) on the aging of C-kit+ hematopoietic progenitor cells (HPCs) via examining the expression of some signaling pathway components.

Methods: For this purpose, bone marrow resident C-kit+ HPCs were enriched by the magnetic-activated cell sorting (MACS) method and were characterized using flow cytometry as well as immunocytochemistry. Cells were treated with LC, and at the end of the treatment period, the cells were subjected to the realtime PCR technique along with a western blotting assay for measurement of the telomere length and assessment of protein expression, respectively.

Results: The results showed that 0.2 mM LC caused the elongation of the telomere length and increased the TERT protein expression. In addition, a significant increase was observed in the protein expression of p38, p53, BCL2, and p16 as key components of the telomere-dependent pathway.

Conclusion: It can be concluded that LC can increase the telomere length as an effective factor in increasing the cell survival and maintenance of the C-kit+ HPCs via these signaling pathway components.

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来源期刊
Current stem cell research & therapy
Current stem cell research & therapy CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
4.20
自引率
3.70%
发文量
197
审稿时长
>12 weeks
期刊介绍: Current Stem Cell Research & Therapy publishes high quality frontier reviews, drug clinical trial studies and guest edited issues on all aspects of basic research on stem cells and their uses in clinical therapy. The journal is essential reading for all researchers and clinicians involved in stem cells research.
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