Kai Dan, Prabhakaran Molamma P, Jin Guorui, Tian Lingling, Ramakrishna Seeram
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore.
Institute of Materials Research and Engineering (IMRE), Singapore.
J Tissue Eng Regen Med. 2017 Apr;11(4):1002-1010. doi: 10.1002/term.1999. Epub 2015 Jan 29.
Heart disease, especially myocardial infarction (MI), has become the leading cause of death all over the world, especially since the myocardium lacks the ability to regenerate after infarction. The capability of mesenchymal stem cells (MSCs) to differentiate into the cardiac lineage holds great potential in regenerative medicine for MI treatment. In this study, we investigated the potential of human MSCs (hMSCs) to differentiate into cardiomyogenic cell lineages, using 5-azacytidine (5-aza) on electrospun poly(ε-caprolactone)-gelatin (PCL-gelatin) nanofibrous scaffolds. Immunofluorescence staining analysis showed that after 15 days of in vitro culture the hMSCs differentiated to cardiomyogenic cells on PCL-gelatin (PG) nanofibers and expressed a higher level of cardiac-specific proteins, such as α-actinin and troponin-T, compared to the MSC-differentiated CMs on tissue culture plates (control). To further induce the cardiac differentiation, vascular endothelial growth factor (VEGF) was incorporated into the nanofibers by blending or co-axial electrospinning, and in vitro release study showed that the growth factor could cause sustained release of VEGF from the nanofibers for a period of up to 21 days. The incorporation of VEGF within the nanofibers improved the proliferation of MSCs and, more importantly, enhanced the expression of cardiac-specific proteins on PG-VEGF nanofibers. Our study demonstrated that the electrospun PG nanofibers encapsulated with VEGF have the ability to promote cardiac differentiation of hMSCs, and might be promising scaffolds for myocardial regeneration. Copyright © 2015 John Wiley & Sons, Ltd.
心脏病，尤其是心肌梗死（MI），已成为全球主要的死亡原因，特别是由于心肌梗死后心肌缺乏再生能力。间充质干细胞（MSCs）分化为心脏谱系的能力在用于MI治疗的再生医学中具有巨大潜力。在本研究中，我们使用5-氮杂胞苷（5-aza）处理电纺聚（ε-己内酯）-明胶（PCL-明胶）纳米纤维支架，研究了人MSCs（hMSCs）分化为心肌源性细胞谱系的潜力。免疫荧光染色分析表明，体外培养15天后，hMSCs在PCL-明胶（PG）纳米纤维上分化为心肌细胞，与组织培养板（对照）上MSC分化的心肌细胞相比，表达更高水平的心脏特异性蛋白，如α-肌动蛋白和肌钙蛋白-T。为了进一步诱导心脏分化，通过共混或同轴电纺将血管内皮生长因子（VEGF）掺入纳米纤维中，体外释放研究表明，生长因子可使VEGF从纳米纤维中持续释放长达21天。纳米纤维中VEGF的掺入改善了MSCs的增殖，更重要的是，增强了PG-VEGF纳米纤维上心脏特异性蛋白的表达。我们的研究表明，包裹有VEGF的电纺PG纳米纤维具有促进hMSCs心脏分化的能力，可能是用于心肌再生的有前景的支架。版权所有©2015 John Wiley & Sons, Ltd.
