Department of Applied Bioscience, CHA University, Seoul, Korea.
Stem Cells Dev. 2013 Jan 1;22(1):158-68. doi: 10.1089/scd.2012.0167. Epub 2012 Aug 13.
Hypoxia induces the survival and regenerative potential of adipose-derived stem cells (ASCs), but there are tremendous needs to find alternative methods for ASC preconditioning. Therefore, this work investigated: (1) the ability of low-dose ultraviolet B (UVB) radiation to stimulate the survival, migration, and tube-forming activity of ASCs in vitro; (2) the ability of UVB preconditioning to enhance the hair growth-promoting capacity of ASCs in vivo; and (3) the mechanism of action for ASC stimulation by UVB. Although high-dose UVB decreased the proliferation of ASCs, low-dose (10 or 20 mJ/cm(2)) treatment increased their survival, migration, and tube-forming activity. In addition, low-dose UVB upregulated the expression of ASC-derived growth factors, and a culture medium conditioned by UVB-irradiated ASCs increased the proliferation of dermal papilla and outer root sheet cells. Notably, injection of UVB-preconditioned ASCs into C(3)H/HeN mice significantly induced the telogen-to-anagen transition and increased new hair weight in vivo. UVB treatment significantly increased the generation of reactive oxygen species (ROS) in cultured ASCs, and inhibition of ROS generation by diphenyleneiodonium chloride (DPI) significantly attenuated UVB-induced ASC stimulation. Furthermore, NADPH oxidase 4 (Nox4) expression was induced in ASCs by UVB irradiation, and Nox4 silencing by small interfering RNA, like DPI, significantly reduced UVB-induced ROS generation. These results suggest that the primary involvement of ROS generation in UVB-mediated ASC stimulation occurs via the Nox4 enzyme. This is the first indication that a low dose of UVB radiation and/or the control of ROS generation could potentially be incorporated into a novel ASC preconditioning method for hair regeneration.
低剂量紫外线 B（UVB）辐射可刺激脂肪来源干细胞（ASCs）的存活和再生潜能，但仍需要寻找 ASC 预处理的替代方法。因此，本研究旨在：（1）研究低剂量 UVB 辐射刺激 ASC 体外存活、迁移和管状形成活性的能力；（2）研究 UVB 预处理增强 ASC 体内促毛发生长能力的能力；（3）研究 UVB 刺激 ASC 的作用机制。尽管高剂量 UVB 会降低 ASC 的增殖能力，但低剂量（10 或 20 mJ/cm(2)) 处理可增加其存活率、迁移和管状形成活性。此外，低剂量 UVB 上调了 ASC 衍生生长因子的表达，由 UVB 照射的 ASC 产生的培养基可增加真皮乳头和外根鞘细胞的增殖。值得注意的是，将经 UVB 预处理的 ASC 注射到 C(3)H/HeN 小鼠体内可显著诱导休止期向生长期的转化，并增加体内新毛重量。UVB 处理可显著增加培养的 ASC 中活性氧（ROS）的产生，而二苯基碘（DPI）抑制 ROS 的产生可显著减弱 UVB 诱导的 ASC 刺激。此外，UVB 照射可诱导 ASC 中 NADPH 氧化酶 4（Nox4）的表达，而 Nox4 沉默（通过 siRNA）与 DPI 一样，可显著减少 UVB 诱导的 ROS 生成。这些结果表明，ROS 的产生是 UVB 介导的 ASC 刺激的主要参与因素，这首次表明低剂量 UVB 辐射和/或 ROS 生成的控制可能被纳入新的 ASC 预处理方法以促进毛发生长。
