Department of Plastic and Reconstructive Surgery, Korea University Medical Center, Gojan 1-dong, Danwon-gu, Ansan-si, Gyeonggi-do 425-707, Republic of Korea.
Exp Cell Res. 2013 Oct 15;319(17):2526-34. doi: 10.1016/j.yexcr.2013.04.014. Epub 2013 May 25.
Mesenchymal stem cells (MSCs) hold great promise for the field of tissue regeneration. Because only a limited number of MSCs can be obtained from each donor site, it is important to establish standard methods for MSC expansion using growth and trophic factors. Thymosin β4 (Tβ4) is a novel trophic factor that has antimicrobial effects and the potential to promote tissue repair. Tβ4 is a ubiquitous, naturally-occurring peptide in the wound bed. Therefore, the relationship between Tβ4 and MSCs, especially adjacent adipose tissue-derived stem cells (ASCs), merits consideration. Exogenous Tβ4 treatment enhanced the proliferation of human ASCs, resulting in prominent nuclear localization of PCNA immunoreactivity. In addition, exogenous Tβ4 also increased IL-8 secretion and blocking of IL-8 with neutralizing antibodies decreased Tβ4-induced ASC proliferation, suggesting that IL-8 is a critical mediator of Tβ4-enhanced proliferation. Moreover, Tβ4 activated phosphorylation of ERK1/2 and increased the nuclear translocation of NF-κB. These observation provide that Tβ4 promotes the expansion of human ASCs via an IL-8-dependent mechanism that involves the ERK and NF-κB pathways. Therefore, Tβ4 could be used as a tool for MSC expansion in cell therapeutics.
间充质干细胞（MSCs）在组织再生领域具有巨大的应用前景。由于每个供体部位只能获得有限数量的 MSCs，因此使用生长和营养因子建立 MSC 扩增的标准方法非常重要。胸腺素β4（Tβ4）是一种新型的营养因子，具有抗菌作用，并具有促进组织修复的潜力。Tβ4 是伤口床中普遍存在的天然肽。因此，Tβ4 与 MSCs，尤其是相邻的脂肪组织来源的干细胞（ASCs）之间的关系值得考虑。外源性 Tβ4 处理增强了人 ASC 的增殖，导致 PCNA 免疫反应性的明显核定位。此外，外源性 Tβ4 还增加了 IL-8 的分泌，并且用中和抗体阻断 IL-8 减少了 Tβ4 诱导的 ASC 增殖，表明 IL-8 是 Tβ4 增强增殖的关键介质。此外，Tβ4 激活了 ERK1/2 的磷酸化，并增加了 NF-κB 的核转位。这些观察结果表明，Tβ4 通过涉及 ERK 和 NF-κB 途径的 IL-8 依赖性机制促进人 ASC 的扩增。因此，Tβ4 可以用作细胞治疗中 MSC 扩增的工具。
