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首页> 外文期刊>Journal of tissue engineering and regenerative medicine >A collagen cardiac patch incorporating alginate microparticles permits the controlled release of hepatocyte growth factor and insulin-like growth factor-1 to enhance cardiac stem cell migration and proliferation
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A collagen cardiac patch incorporating alginate microparticles permits the controlled release of hepatocyte growth factor and insulin-like growth factor-1 to enhance cardiac stem cell migration and proliferation

机译:包含藻酸盐微粒的胶原蛋白心脏贴片允许肝细胞生长因子和胰岛素样生长因子-1的控制释放,以增强心脏干细胞迁移和增殖

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摘要

Cardiac stem cells (CSCs) represent a logical cell type to exploit as a regenerative treatment option for tissue damage accrued as a result of a myocardial infarction. However, the isolation and expansion of CSCs prior to cell transplantation is time consuming, costly and invasive, and the reliability of cell expansion may also prove to be a major obstacle in the clinical application of CSC-based transplantation therapy after a myocardial infarction. In order to overcome this, we propose the incorporation of growth factor-eluting alginate microparticles into collagen-based scaffolds as an implantable biomaterial to promote the recruitment and expansion of CSCs in the myocardium. In order to obtain scaffolds able to enhance the motogenic and proliferative potential of CSCs, the aim of this work was to achieve a sustained delivery of both hepatocyte growth factor and insulin-like growth factor-1. Both proteins were initially encapsulated in alginate microparticles by spray drying and subsequently incorporated into a collagen scaffold. Microparticles were seen to homogeneously distribute through the interconnected scaffold pore structure. The resulting scaffolds were capable of extending the release of both proteins up to 15days, a three-fold increase over non-encapsulated proteins embedded in the scaffolds. In vitro assays with isolated CSCs demonstrated that the sustained release of both bioactive proteins resulted in an increased motogenic and proliferative effect. As presently practiced, the isolation and expansion of CSCs for autologous cell transplantation is slow, expensive and difficult to attain. Thus, there is a need for strategies to specifically activate in situ the intrinsic cardiac regenerative potential represented by the CSCs using combinations of growth factors obviating the need for cell transplantation. By favouring the natural regenerative capability of CSCs, it is hypothesized that the cardiac patch presented here will result in positive therapeutic outcomes in MI and heart failure patients in the future. Copyright (C) 2016 John Wiley & Sons, Ltd.
机译:心脏干细胞(CSCs)代表逻辑细胞类型,作为由于心肌梗死而累积的组织损伤的再生治疗选择。然而,在细胞移植之前CSCs的分离和扩展是耗时,昂贵和侵入性,并且细胞扩张的可靠性也可能被证明是CSC基移植治疗后心肌梗死后的临床应用中的主要障碍。为了克服这一点,我们提出将生长因子洗脱的藻酸盐微粒掺入基于胶原基的支架中,作为可植入的生物材料,以促进心肌中CSC的募集和扩展。为了获得能够增强CSC的常温和增殖性潜力的支架,这项工作的目的是达到肝细胞生长因子和胰岛素样生长因子-1的持续递送。通过喷雾干燥最初将两个蛋白质包封在藻酸盐微粒中,随后掺入胶原支架中。看到微粒通过互连的支架孔结构均匀地分布。得到的支架能够将两种蛋白质的释放延伸至15天,在支架中嵌入的非包封蛋白增加三倍。具有分离的CSC的体外测定证明,生物活性蛋白的持续释放导致血泡和增殖效应增加。如目前的实践,用于自体细胞移植的CSCs的分离和扩展是缓慢,昂贵且难以达到的。因此,需要使用避免细胞移植需要的生长因子的组合,具体地对CSCs表示的内在心脏再生潜力进行特异性激活策略。通过有利于CSC的自然再生能力,假设此处呈现的心脏贴剂将在未来产生MI和心力衰竭患者的阳性治疗结果。版权所有(c)2016 John Wiley&Sons,Ltd。

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