Matrix stiffness regulates myocardial differentiation of human umbilical cord mesenchymal stem cells.
Matrix stiffness regulates myocardial differentiation of human umbilical cord mesenchymal stem cells.
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基质硬度调节人脐带间充质干细胞的心肌分化
DOI：
10.18632/aging.202244
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发表时间：
2020-12-09
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Sun Y;Liu J;Xu Z;Lin X;Zhang X;Li L;Li Y
心肌梗塞是一种死亡率较高的心血管疾病。人脐带间充质干细胞（hUC-MSCs）具有很强的自我更新能力和多能性，为替代受损心肌细胞提供了可能。 hUC-MSC 在聚丙烯酰胺水凝胶上培养，其硬度相当于 13-16kPa 和 62-68kPa 的杨氏模量，模拟健康心脏组织和纤维化心肌的硬度。 RT-PCR和Western Blot检测早期心肌标志物Nkx2.5、GATA4、Mesp1和成熟心肌标志物cTnT、cTnI、α-actin的表达情况，表明软基质（13-16 kPa）较硬基质（62-68 kPa）更容易诱导hUC-MSCs向心肌分化。压电是机械敏感的非选择性阳离子通道。第1天Piezo1的表达随着硬度梯度1-10kPa、13-16kPa、35-38kPa和62-68kPa的增加而增加，但Piezo2的表达不规则。整合素β1和钙离子的表达在硬基质上也高于软基质上。 hUC-MSC 在基质硬度为 13-16 kPa 时倾向于分化为心肌。基质硬度、Piezo1 和心肌分化之间的关系需要进一步验证。
Myocardial infarction is a cardiovascular disease with high mortality. Human umbilical cord mesenchymal stem cells (hUC-MSCs) with strong self-renewal capacity and multipotency, provide the possibility of replacing injured cardiomyocytes. hUC-MSCs were cultured on polyacrylamide hydrogels with stiffnesses corresponding to Young's modulus of 13-16kPa and 62-68kPa which mimic the stiffnesses of healthy heart tissue and fibrotic myocardium. The expression of early myocardial markers Nkx2.5, GATA4, Mesp1 and the mature myocardial markers cTnT, cTnI, α-actin were detected by RT-PCR and Western Blot, which showed that soft matrix (13-16 kPa) tended to induce the differentiation of hUC-MSCs into myocardium, compared with stiff matrix (62-68 kPa). Piezos are mechanically sensitive non-selective cation channels. The expression of Piezo1 increased with the stiffness gradient of 1-10kPa, 13-16kPa, 35-38kPa and 62-68kPa on the 1st day, but Piezo2 expression was irregular. The expression of integrin β1 and calcium ions were also higher on stiff substrate than on soft substrate. hUC-MSCs tend to differentiate into myocardium on the matrix stiffness of 13-16 kPa. The relationship among matrix stiffness, Piezo1 and myocardial differentiation needs further validation.