Transplantation of Cyclic Stretched Fibroblasts Accelerates the Wound-Healing Process in Streptozotocin-Induced Diabetic Mice
Transplantation of Cyclic Stretched Fibroblasts Accelerates the Wound-Healing Process in Streptozotocin-Induced Diabetic Mice
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DOI：
10.3727/096368912x663541
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发表时间：
2014-01-01
影响因子：
3.3
通讯作者：
Son, Youngsook
中科院分区：
文献类型：
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作者：
Lee, Eunkyung;Kim, Do Yeon;Son, Youngsook
机械刺激是许多细胞存活和增殖的已知调节剂，包括内皮细胞、平滑肌细胞和骨髓源性间充质干细胞。在这项研究中，我们发现机械应变可以防止细胞凋亡并增加体外真皮成纤维细胞的粘附能力，从而赋予成纤维细胞移植到糖尿病小鼠全层伤口后体内的生存优势。以0.5 Hz的频率和20%的最大伸长的循环拉伸刺激通过细胞外信号调节激酶（ERK）、c-Jun N-末端激酶（JNK）和丝氨酸/苏氨酸激酶Akt（AKT）的激活介导的细胞存活。成纤维细胞的拉伸增加了细胞外基质蛋白的合成和更致密的粘着斑结构的形成，这两者都是成纤维细胞粘附所需的。拉伸的成纤维细胞还上调血管内皮生长因子（VEGF）和基质细胞衍生因子-la（SDF-1 α）的表达，这增强了体内伤口愈合。事实上，与未拉伸的对照细胞相比，在链脲佐菌素诱导的糖尿病小鼠的伤口环境中，机械拉伸预处理允许移植的成纤维细胞更好地存活，从而加速这些小鼠的伤口愈合过程。
Mechanical stimulation is a known modulator of survival and proliferation for many cells, including endothelial cells, smooth muscle cells, and bone marrow-derived mesenchymal stem cells. In this study, we found that mechanical strain prevents apoptosis and increases the adhesive ability of dermal fibroblasts in vitro and thus confers the survival advantage in vivo after transplantation of fibroblasts into the full-thickness wound of diabetic mice. Cyclic stretch at a frequency of 0.5 Hz and maximum elongation of 20% stimulates cellular survival mediated by the activation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and the serine/threonine kinase Akt (AKT). Stretching of the fibroblasts increases the synthesis of extracellular matrix proteins and the formation of denser focal adhesion structures, both of which are required for fibroblast adhesion. The stretched fibroblasts also upregulate the expression of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-la (SDF-1 alpha), which enhanced wound healing in vivo. Indeed, preconditioning with mechanical stretch allows better survival of the transplanted fibroblasts, when compared to unstretched control cells, in the wound environment of mice with streptozotocin-induced diabetes and thus accelerates the wound-healing process in these mice.