Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro
Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro
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DOI：
10.1155/2016/8364382
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发表时间：
2016-01-01
影响因子：
4.3
通讯作者：
Davis, Michael E.
中科院分区：
文献类型：
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作者：
French, Kristin M.;Maxwell, Joshua T.;Davis, Michael E.
心脏祖细胞（CPC）已迅速进入临床试验，但对它们与微环境的相互作用知之甚少。微环境中存在的信号线索随着发育和疾病而变化。这项工作的目的是评估两个不同的信号部分对CPC的影响：周期性双轴应变和细胞外基质。我们评估了改善CPC治疗的四个终点：旁分泌信号，增殖，连接蛋白43表达和对齐。血管内皮生长因子A（约900 pg/mL）由在纤连蛋白和胶原I上培养的CPC分泌。应用机械应变增加血管内皮生长因子A分泌2-4倍的CPC上培养的聚-L-赖氨酸，层粘连蛋白，或天然来源的心脏细胞外基质。CPC增殖至少25%以上的纤连蛋白比其他基质，特别是较低的应变幅度。在5%应变下，连接蛋白43在纤连蛋白上的表达最高。随着应变幅度的增加，CPCs在I型胶原和天然来源的心脏细胞外基质上培养时，连接蛋白43的表达下降了60%。当在纤连蛋白或胶原I上培养时，循环机械应变诱导最强的CPC排列。这项研究表明，在纤连蛋白上以5%的应变幅度培养CPC对于它们的血管内皮生长因子A分泌、增殖、连接蛋白43表达和排列是最佳的。
Cardiac progenitor cells (CPCs) have rapidly advanced to clinical trials, yet little is known regarding their interaction with the microenvironment. Signaling cues present in the microenvironment change with development and disease. This work aims to assess the influence of two distinct signaling moieties on CPCs: cyclic biaxial strain and extracellular matrix. We evaluate four endpoints for improving CPC therapy: paracrine signaling, proliferation, connexin43 expression, and alignment. Vascular endothelial growth factor A (about 900 pg/mL) was secreted by CPCs cultured on fibronectin and collagen I. The application of mechanical strain increased vascular endothelial growth factor A secretion 2-4-fold for CPCs cultured on poly-L-lysine, laminin, or a naturally derived cardiac extracellular matrix. CPC proliferation was at least 25% higher on fibronectin than that on other matrices, especially for lower strain magnitudes. At 5% strain, connexin43 expression was highest on fibronectin. With increasing strain magnitude, connexin43 expression decreased by as much as 60% in CPCs cultured on collagen I and a naturally derived cardiac extracellular matrix. Cyclic mechanical strain induced the strongest CPC alignment when cultured on fibronectin or collagen I. This study demonstrates that culturing CPCs on fibronectin with 5% strain magnitude is optimal for their vascular endothelial growth factor A secretion, proliferation, connexin43 expression, and alignment.