Biophysical cues enhance myogenesis of human adipose derived stem/stromal cells.
Biophysical cues enhance myogenesis of human adipose derived stem/stromal cells.
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DOI：
10.1016/j.bbrc.2013.07.049
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发表时间：
2013-08-16
影响因子：
3.1
通讯作者：
Grayson WL
中科院分区：
文献类型：
--
作者：
Yilgor Huri P;Cook CA;Hutton DL;Goh BC;Gimble JM;DiGirolamo DJ;Grayson WL
基于脂肪干/基质细胞（ASC）的组织工程肌肉移植物可以为受损肌肉的再生提供自体移植物的有效替代疗法（自体移植物因其可用性而受到限制）。然而，目前 ASC 的生肌潜力因其分化成成肌细胞的效率较低而受到限制。本研究的目的是通过提供生物物理刺激（11% 循环单轴应变，0.5 Hz，1 小时/天）来模拟天然肌肉微环境中存在的线索，从而增强人类 ASC 对生化线索的生肌反应。仅用生肌诱导培养基诱导后，ASC 就会伸长并融合。然而，随着生物物理刺激的增加，它们的生肌特征显着增强。与静态条件相比，动态条件下第 21 天每个细胞的细胞核增加了约 4.5 倍（分别为 23.3 ± 7.3 与 5.2 ± 1.6），它们与应变方向几乎呈 45° 排列，并且表现出显着更高的肌源蛋白（结蛋白、myoD 和肌球蛋白重链）表达。这些结果表明，模仿单层 ASC 培养物中天然肌肉微环境固有的生物物理线索可显着改善其沿生肌谱系的分化。
Adipose-derived stem/stromal cell (ASC)-based tissue engineered muscle grafts could provide an effective alternative therapy to autografts – which are limited by their availability – for the regeneration of damaged muscle. However, the current myogenic potential of ASCs is limited by their low differentiation efficiency into myoblasts. The aim of this study was to enhance the myogenic response of human ASCs to biochemical cues by providing biophysical stimuli (11% cyclic uniaxial strain, 0.5 Hz, 1 h/day) to mimic the cues present in the native muscle microenvironment. ASCs elongated and fused upon induction with myogenic induction medium alone. Yet, their myogenic characteristics were significantly enhanced with the addition of biophysical stimulation; the nuclei per cell increased approximately 4.5-fold by day 21 in dynamic compared to static conditions (23.3 ± 7.3 vs. 5.2 ± 1.6, respectively), they aligned at almost 45° to the direction of strain, and exhibited significantly higher expression of myogenic proteins (desmin, myoD and myosin heavy chain). These results demonstrate that mimicking the biophysical cues inherent to the native muscle microenvironment in monolayer ASC cultures significantly improves their differentiation along the myogenic lineage.