Bose Bipasha, Shenoy P Sudheer
School of Biological Sciences, Nanyang Technological University, 60, Nanyang Drive, Singapore 637551, Singapore.
Int J Biochem Cell Biol. 2016 Jan;70:1-12. doi: 10.1016/j.biocel.2015.10.009. Epub 2015 Oct 13.
Aging is accompanied by the functional decline of cells, tissues, and organs, as well as, a striking increase in susceptibility to a wide range of diseases. Within a tissue, both differentiated cells and adult stem cells are susceptible to intrinsic and extrinsic changes while aging. Muscle derived stem cells (MDSCs) are tissue specific stem cells which have been studied well for their multipotential nature. Although there are reports relating to diminished function and regenerative capacity of aged MDSCs as compared to their young counterparts, not much has been reported relating to the concomitant gain in unipotent nature of aged MDSCs. In this study, we report an inverse correlation between aging and expression of adult/mesenchymal stem cell markers and a direct correlation between aging and myogenecity in MDSCs. Aged MDSCs were able to generate a greater number of dystrophin positive myofibres, as compared to, the young MDSCs when transplanted in muscle of dystrophic mice. Our data, therefore, suggests that aging stress adds to the decline in stem cell characteristics with a concomitant increase in unipotency, in terms of, myogenecity of MDSCs. This study, hence, also opens the possibilities of using unipotent aged MDSCs as potential candidates for transplantation in patients with muscular dystrophies.
衰老伴随着细胞、组织和器官的功能衰退,以及对多种疾病易感性的显著增加。在一个组织内,分化细胞和成年干细胞在衰老过程中都易受内在和外在变化的影响。肌肉衍生干细胞(MDSCs)是组织特异性干细胞,因其多能性已得到充分研究。尽管有报道称,与年轻的MDSCs相比,衰老的MDSCs功能和再生能力有所下降,但关于衰老的MDSCs单能性增加的报道却不多。在本研究中,我们报告了衰老与成年/间充质干细胞标志物表达之间呈负相关,以及衰老与MDSCs的肌源性之间呈正相关。与年轻的MDSCs相比,当将衰老的MDSCs移植到营养不良小鼠的肌肉中时,它们能够产生更多抗肌萎缩蛋白阳性的肌纤维。因此,我们的数据表明,衰老应激加剧了干细胞特性的下降,同时伴随着MDSCs肌源性方面单能性的增加。因此,本研究也为将单能性衰老MDSCs作为肌肉营养不良患者移植的潜在候选者开辟了可能性