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用于间充质干细胞心脏治疗的藻酸盐支架:藻酸盐组成的影响。

Alginate scaffolds for mesenchymal stem cell cardiac therapy: influence of alginate composition.

机构信息

Université de Toulouse, CIRIMAT, UPS-INPT-CNRS, Faculté de Pharmacie, Toulouse, France.

出版信息

Cell Transplant. 2012;21(9):1969-84. doi: 10.3727/096368912X647252. Epub 2012 Jul 5.

Abstract

Despite the success of alginate scaffolds and mesenchymal stem cells (MSCs) therapy in cardiac failure treatment, the impact of the physicochemical environment provided by alginate matrices on cell behavior has never been investigated. The purpose of this work was double: to determine the alginate composition influence on (1) encapsulated rat MSC viability, paracrine activity, and phenotype in vitro and (2) cardiac implantability and in vivo biocompatibility of patch shape scaffolds. Two alginates, differing in composition and thus presenting different mechanical properties when hydrogels, were characterized. In both cases, encapsulated MSC viability was maintained at around 75%, and their secretion characteristics were retained 28 days postencapsulation. In vivo study revealed a high cardiac compatibility of the tested alginates: cardiac parameters were maintained, and rats did not present any sign of infection. Moreover, explanted hydrogels appeared surrounded by a vascularized tissue. However, scaffold implantability was highly dependent on alginate composition. G-type alginate patches, presenting higher elastic and Young moduli than M-type alginate patches, showed a better implantation easiness and were the only ones that maintained their shape and morphology in vivo. As a consequence of alginate chemical composition and resulting hydrogel structuration, G-type alginate hydrogels appear to be more adapted for cardiac implantation.

摘要

尽管海藻酸盐支架和间充质干细胞 (MSCs) 疗法在心力衰竭治疗中取得了成功,但海藻酸盐基质提供的物理化学环境对细胞行为的影响从未被研究过。这项工作的目的是双重的:一是确定海藻酸盐组成对(1)体外包裹的大鼠 MSC 活力、旁分泌活性和表型的影响,以及(2)贴片形状支架的心脏可植入性和体内生物相容性的影响。两种海藻酸盐在组成上有所不同,因此在水凝胶中具有不同的机械性能,对其进行了表征。在这两种情况下,包裹的 MSC 活力保持在 75%左右,并且它们的分泌特性在包裹后 28 天内得以保留。体内研究表明,所测试的海藻酸盐具有很高的心脏相容性:心脏参数得以维持,并且大鼠没有任何感染的迹象。此外,植入的水凝胶似乎被血管化组织包围。然而,支架的可植入性高度依赖于海藻酸盐的组成。G 型海藻酸盐贴片的弹性和杨氏模量均高于 M 型海藻酸盐贴片,其植入更容易,并且是唯一在体内保持其形状和形态的贴片。由于海藻酸盐的化学成分和由此产生的水凝胶结构,G 型海藻酸盐水凝胶似乎更适合心脏植入。

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