Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2733-40. doi: 10.1161/ATVBAHA.112.300230. Epub 2012 Sep 6.
Mesenchymal stem cells are useful for vascular regeneration of injured tissues. Macrophages are involved in acute or chronic inflammatory diseases, and interleukin-1β (IL-1β), a proinflammatory cytokine, plays a key role in the activation of macrophages within injured tissues. To explore the role of macrophages on mesenchymal stem cell-mediated vascular regeneration, we examined the effects of IL-1β-activated macrophages on differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) to smooth muscle cells (SMCs) and the vascular regenerative capacity of the differentiated SMCs in a hindlimb ischemia animal model.
We demonstrate that IL-1β-conditioned medium from RAW 264.7 macrophages induces differentiation of human adipose tissue-derived mesenchymal stem cells to α-smooth muscle actin-positive SMCs, and the differentiated SMCs exhibited increased contractility in response to KCl and carbachol treatment. Transplantation of the differentiated SMCs attenuated severe hindlimb ischemia and promoted vascular regeneration. IL-1β treatment stimulated secretion of prostaglandin F(2α) from RAW 264.7 cells. Small interfering RNA-mediated silencing of the prostaglandin F(2α) receptor completely abrogated IL-1β conditioned medium-stimulated α-smooth muscle actin expression. Moreover, prostaglandin F(2α) treatment stimulated expression of α-smooth muscle actin in human adipose tissue-derived mesenchymal stem cells.
These results suggest that IL-1β-activated macrophages promote differentiation of human adipose tissue-derived mesenchymal stem cells to SMCs through a prostaglandin F(2α)-mediated paracrine mechanism.
间充质干细胞可用于损伤组织的血管再生。巨噬细胞参与急性或慢性炎症性疾病，白细胞介素-1β（IL-1β）作为一种前炎性细胞因子，在损伤组织中巨噬细胞的激活中发挥关键作用。为了探索巨噬细胞在间充质干细胞介导的血管再生中的作用，我们研究了 IL-1β激活的巨噬细胞对人脂肪组织来源的间充质干细胞（hASCs）向平滑肌细胞（SMCs）分化的影响，以及分化的 SMCs 在大鼠后肢缺血动物模型中的血管再生能力。
我们证明 RAW 264.7 巨噬细胞的 IL-1β条件培养基诱导人脂肪组织来源的间充质干细胞向α-平滑肌肌动蛋白阳性 SMCs 的分化，分化的 SMCs 对 KCl 和卡巴胆碱处理的反应性增加收缩力。分化的 SMCs 的移植减轻了严重的后肢缺血并促进了血管再生。IL-1β处理刺激 RAW 264.7 细胞前列腺素 F(2α)的分泌。前列腺素 F(2α)受体的小干扰 RNA 介导的沉默完全阻断了 IL-1β条件培养基刺激的α-平滑肌肌动蛋白表达。此外，前列腺素 F(2α)处理刺激人脂肪组织来源的间充质干细胞中α-平滑肌肌动蛋白的表达。
这些结果表明，IL-1β激活的巨噬细胞通过前列腺素 F(2α)介导的旁分泌机制促进人脂肪组织来源的间充质干细胞向 SMCs 的分化。
