Khorraminejad-Shirazi Mohammadhossein, Farahmandnia Mohammad, Kardeh Bahareh, Estedlal Alireza, Kardeh Sina, Monabati Ahmad
Cell and Molecular Medicine Student Research Group, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
Cell and Molecular Medicine Student Research Group, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
Hematol Oncol Stem Cell Ther. 2018 Dec;11(4):189-194. doi: 10.1016/j.hemonc.2017.08.001. Epub 2017 Oct 19.
In recent years, tissue regeneration has become a promising field for developing stem cell-based transplantation therapies for human patients. Adult stem cells are affected by the same aging mechanisms that involve somatic cells. One of the mechanisms involved in cellular aging is hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and disruption of 5' adenosine monophosphate-activated protein kinase (AMPK). Aging of stem cells results in their impaired regenerative capacity and depletion of stem cell pools in adult tissue, which results in lower efficacy of stem cell therapy. By utilizing an effective therapeutic intervention for aged stem cells, stem cell therapy can become more promising for future application. mTORC1 inhibition is a practical approach to preserve the stem cell pool. In this article, we review the dynamic interaction between sirtuin (silent mating type information regulation 2 homolog) 1, AMPK, and mTORC1. We propose that using AMPK activators such as 5-aminoimidazole-4-carboxamide ribonucleotide, A769662, metformin, and oxidized nicotinamide adenine dinucleotide (NAD) are practical ways to be employed for achieving better optimized results in stem cell-based transplantation therapies.
近年来，组织再生已成为为人类患者开发基于干细胞的移植疗法的一个有前景的领域。成体干细胞受到与体细胞相同的衰老机制影响。细胞衰老涉及的机制之一是雷帕霉素复合物1（mTORC1）的过度激活和5' 单磷酸腺苷激活蛋白激酶（AMPK）的破坏。干细胞衰老导致其再生能力受损以及成体组织中干细胞池的耗竭，从而导致干细胞治疗效果降低。通过对衰老干细胞进行有效的治疗干预，干细胞治疗在未来应用中可能会更有前景。抑制mTORC1是维持干细胞池的一种切实可行的方法。在本文中，我们综述了沉默信息调节因子2同源物1（SIRT1）、AMPK和mTORC1之间的动态相互作用。我们提出，使用AMPK激活剂，如5-氨基咪唑-4-甲酰胺核糖核苷酸、A769662、二甲双胍和氧化型烟酰胺腺嘌呤二核苷酸（NAD），是在基于干细胞的移植疗法中获得更好优化结果的切实可行的方法。
