Ok Jeong Su, Song Seon Beom, Hwang Eun Seong
Department of Life Science, University of Seoul, Seoul, Korea.
Int J Stem Cells. 2018 May 30;11(1):13-25. doi: 10.15283/ijsc18033.
Therapies using mesenchymal stem cells (MSCs) generally require substantial expansion of cell populations. However, the replicative life span of MSCs is limited and their multipotency declines over continued passages, imposing a limitation on their application especially in aged individuals. In an effort to increase MSC life span, we tested the effects of nicotinamide (NAM), a precursor of NAD⁺ that has been shown to reduce reactive oxygen species generation and delay the onset of replicative senescence in fibroblasts.
Bone marrow stem cells (BMSCs) from healthy donors were cultivated in the presence of 5 mM NAM until the end of their life span. The levels of proliferation and differentiation to osteogenic, adipogenic, and chondrogenic lineages of BMSCs were compared between populations incubated in the absence or presence of NAM.
The replicative life span was substantially increased with a significant delay in the onset of senescence, and differentiation to all tested lineages was increased. Furthermore, differentiation was sustained and the adipogenic switch from osteogenesis to adipogenesis was attenuated in late-passage BMSCs.
NAM could be considered as an important biological agent to expand and sustain the multipotency of BMSCs and thus broaden the application of stem cells in cell therapies.
使用间充质干细胞（MSC）的疗法通常需要大量扩增细胞群体。然而，MSC的复制寿命有限，且随着传代次数的增加其多能性会下降，这对其应用造成了限制，尤其是在老年个体中。为了延长MSC的寿命，我们测试了烟酰胺（NAM）的作用，NAM是NAD⁺的前体，已被证明可减少活性氧的产生并延缓成纤维细胞复制性衰老的发生。
将来自健康供体的骨髓干细胞（BMSC）在5 mM NAM存在的情况下培养至其寿命结束。比较在有无NAM的情况下培养的BMSC群体在增殖以及向成骨、成脂和成软骨谱系分化方面的水平。
复制寿命显著延长，衰老发生明显延迟，并且向所有测试谱系的分化均增加。此外，在传代后期的BMSC中，分化得以维持，并且从成骨到成脂的脂肪生成转换减弱。
NAM可被视为一种重要的生物制剂，用于扩增和维持BMSC的多能性，从而拓宽干细胞在细胞治疗中的应用。
