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Human Mesenchymal Stem Cells Reendothelialize Porcine Heart Valve Scaffolds: Novel Perspectives in Heart Valve Tissue Engineering

机译:人间充质干细胞reendothelialize猪心脏瓣膜支架:心脏瓣膜组织工程的新观点。

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Heart valve diseases are usually treated by surgical intervention addressed for the replacement of the damaged valve with a biosynthetic or mechanical prosthesis. Although this approach guarantees a good quality of life for patients, it is not free from drawbacks (structural deterioration, nonstructural dysfunction, and reintervention). To overcome these limitations, the heart valve tissue engineering (HVTE) is developing new strategies to synthesize novel types of valve substitutes, by identifying efficient sources of both ideal scaffolds and cells. In particular, a natural matrix, able to interact with cellular components, appears to be a suitable solution. On the other hand, the well-known Wharton's jelly mesenchymal stem cells (WJ-MSCs) plasticity, regenerative abilities, and their immunomodulatory capacities make them highly promising for HVTE applications. In the present study, we investigated the possibility to use porcine valve matrix to regenerate in vitro the valve endothelium by WJ-MSCs differentiated along the endothelial lineage, paralleled with human umbilical vein endothelial cells (HUVECs), used as positive control. Here, we were able to successfully decellularize porcine heart valves, which were then recellularized with both differentiated-WJ-MSCs and HUVECs. Data demonstrated that both cell types were able to reconstitute a cellular monolayer. Cells were able to positively interact with the natural matrix and demonstrated the surface expression of typical endothelial markers. Altogether, these data suggest that the interaction between a biological scaffold and WJ-MSCs allows the regeneration of a morphologically well-structured endothelium, opening new perspectives in the field of HVTE.
机译:心脏瓣膜疾病通常通过外科手术来治疗,该手术涉及用生物合成或机械假体替换受损的瓣膜。尽管这种方法保证了患者良好的生活质量,但也存在一些弊端(结构恶化,非结构性功能障碍和再次干预)。为了克服这些限制,心脏瓣膜组织工程(HVTE)正在开发新策略,以通过识别理想支架和细胞的有效来源来合成新型瓣膜替代物。特别地,能够与细胞成分相互作用的天然基质似乎是合适的解决方案。另一方面,沃顿商学院的果冻间充质干细胞(WJ-MSC)的可塑性,再生能力及其免疫调节能力使它们在HVTE应用中极有希望。在本研究中,我们研究了利用猪瓣膜基质通过沿内皮谱系分化的WJ-MSC与人脐静脉内皮细胞(HUVEC)平行用作体外阳性对照体外再生瓣膜内皮的可能性。在这里,我们能够成功地使猪心脏瓣膜脱细胞,然后再用分化的WJ-MSC和HUVEC对其进行细胞脱细胞。数据表明两种细胞类型都能够重构细胞单层。细胞能够与天然基质发生积极相互作用,并证明了典型的内皮标记物的表面表达。总而言之,这些数据表明生物支架与WJ-MSC之间的相互作用可以使形态良好的内皮细胞再生,从而为HVTE领域开辟了新的前景。

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