Kim Won-Serk, Han Juhee, Hwang Sung-Joo, Sung Jong-Hyuk
Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Department of Dermatology , Seoul , Korea.
Expert Opin Biol Ther. 2014 Aug;14(8):1091-102. doi: 10.1517/14712598.2014.907785. Epub 2014 Apr 8.
The self-renewal and differentiation of stem cells are controlled by both intrinsic factors and the surrounding microenvironment, which is known as the stem cell niche. Although the niches of adipose-derived stem cells (ASCs) are composed of diverse factors within the adipose tissue, the mechanisms by which niches are maintained, regulated and harmonized to support the ASCs are just beginning to be discovered.
This review introduces the recent advances in the anatomic nature of the dynamic in vivo niches of ASCs. Additionally, new findings concerning the signaling pathways involved in the self-renewal, proliferation, differentiation and paracrine mechanisms will be described. Finally, we suggest optimized methods for expanding ASCs in vitro by mimicking the niche factors to enhance the regenerative potential of ASCs.
Fibroblast growth factor 2 is a self-renewal factor that can expand the lifespan of ASCs in long-term culture and platelet-derived growth factor-B/D has most potent mitogenic effects on short-term ASC expansion. Reactive oxygen species donors and stimulators of the phosphoinositide 3-kinase/protein kinase B and MAPK pathways can be used to increase the production yield of ASCs. Additionally, hypoxia can increase the proliferation of ASCs and priming under hypoxic conditions enhances the regenerative potential of ASCs.
干细胞的自我更新和分化受内在因素及周围微环境(即干细胞生态位)的共同控制。尽管脂肪来源干细胞(ASC)的生态位由脂肪组织内的多种因素组成,但维持、调节和协调生态位以支持ASC的机制才刚刚开始被发现。
本综述介绍了ASC在体内动态生态位的解剖学性质的最新进展。此外,还将描述有关自我更新、增殖、分化和旁分泌机制中涉及的信号通路的新发现。最后,我们提出了通过模拟生态位因子在体外扩增ASC的优化方法,以增强ASC的再生潜力。
成纤维细胞生长因子2是一种自我更新因子,可延长ASC在长期培养中的寿命,血小板衍生生长因子-B/D对ASC的短期扩增具有最强的促有丝分裂作用。活性氧供体以及磷酸肌醇3激酶/蛋白激酶B和丝裂原活化蛋白激酶途径的刺激剂可用于提高ASC的产量。此外,缺氧可增加ASC的增殖,缺氧条件下的预处理可增强ASC的再生潜力。