Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, Seoul 02841, Korea.
Int J Mol Sci. 2020 Mar 21;21(6):2166. doi: 10.3390/ijms21062166.
Thymosin β4 (Tβ4) is a G-actin sequestering protein that contributes to diverse cellular activities, such as migration and angiogenesis. In this study, the beneficial effects of combined cell therapy with Tβ4 and human adipose-derived stem cells (hASCs) in a mouse ischemic hindlimb model were investigated. We observed that exogenous treatment with Tβ4 enhanced endogenous mRNA expression and promoted morphological changes (increased cell length) in hASCs. Interestingly, Tβ4 induced the active state of hASCs by up-regulating intracellular signaling pathways including the PI3K/AKT/mTOR and MAPK/ERK pathways. Treatment with Tβ4 significantly increased cell migration and sprouting from microbeads. Moreover, additional treatment with Tβ4 promoted the endothelial differentiation potential of hASCs by up-regulating various angiogenic genes. To evaluate the in vivo effects of the Tβ4-hASCs combination on vessel recruitment, dorsal window chambers were transplanted, and the co-treated mice were found to have a significantly increased number of microvessel branches. Transplantation of hASCs in combination with Tβ4 was found to improve blood flow and attenuate limb or foot loss post-ischemia compared to transplantation with hASCs alone. Taken together, the therapeutic application of hASCs combined with Tβ4 could be effective in enhancing endothelial differentiation and vascularization for treating hindlimb ischemia.
胸腺素 β4（Tβ4）是一种 G-肌动蛋白隔离蛋白，它有助于多种细胞活动，如迁移和血管生成。在这项研究中，研究了 Tβ4 和人脂肪来源干细胞（hASCs）联合细胞治疗在小鼠缺血性后肢模型中的有益效果。我们观察到，外源性 Tβ4 处理增强了内源性 mRNA 表达，并促进了 hASCs 的形态变化（细胞长度增加）。有趣的是，Tβ4 通过上调包括 PI3K/AKT/mTOR 和 MAPK/ERK 通路在内的细胞内信号通路诱导 hASCs 的激活状态。Tβ4 处理显著增加了微珠上的细胞迁移和发芽。此外，Tβ4 的额外处理通过上调各种血管生成基因促进了 hASCs 的内皮分化潜能。为了评估 Tβ4-hASCs 联合治疗对血管募集的体内影响，移植了背部窗室，发现联合治疗的小鼠微血管分支数量明显增加。与单独移植 hASCs 相比，联合移植 hASCs 和 Tβ4 可改善血流并减轻缺血后肢体或足部的损失。综上所述，hASCs 与 Tβ4 联合的治疗应用可能对增强内皮分化和血管生成以治疗后肢缺血有效。
