Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue.
Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue.
复制标题
DOI：
10.1038/ncomms8405
复制
发表时间：
2015-06-17
影响因子：
16.6
通讯作者：
Hollander AP
中科院分区：
文献类型：
--
作者：
Armstrong JPK;Shakur R;Horne JP;Dickinson SC;Armstrong CT;Lau K;Kadiwala J;Lowe R;Seddon A;Mann S;Anderson JLR;Perriman AW;Hollander AP
氧气扩散受限可导致工程组织中中心细胞坏死，当工程组织用于临床应用时，这一问题会加剧。本研究表明，用合成的膜活性肌红蛋白-聚合物-表面活性剂复合物预处理人间充质干细胞（hMSCs）可以提供一个氧气库，能够缓解透明软骨中心的坏死。这是通过开发一种新的基于聚合物-表面活性剂偶联的细胞功能化方法来实现的，这种方法允许将功能蛋白传递到hMSC膜上。这种新方法绕过了使用蛋白质嵌合或基因转染的细胞表面工程的需要，并且我们证明了表面修饰的hMSCs保留了它们增殖和经历多谱系分化的能力。功能化技术是一种简单、通用和无破坏性的技术，除了组织氧合之外，它应该在许多组织工程和细胞治疗中有深远的应用。避免大型工程组织结构中心的中心细胞坏死是体外组织工程的一个重要问题。在这里，作者证明了这个问题可以通过用人工膜结合蛋白充氧人间充质干细胞来克服。
Restricted oxygen diffusion can result in central cell necrosis in engineered tissue, a problem that is exacerbated when engineering large tissue constructs for clinical application. Here we show that pre-treating human mesenchymal stem cells (hMSCs) with synthetic membrane-active myoglobin-polymer–surfactant complexes can provide a reservoir of oxygen capable of alleviating necrosis at the centre of hyaline cartilage. This is achieved through the development of a new cell functionalization methodology based on polymer–surfactant conjugation, which allows the delivery of functional proteins to the hMSC membrane. This new approach circumvents the need for cell surface engineering using protein chimerization or genetic transfection, and we demonstrate that the surface-modified hMSCs retain their ability to proliferate and to undergo multilineage differentiation. The functionalization technology is facile, versatile and non-disruptive, and in addition to tissue oxygenation, it should have far-reaching application in a host of tissue engineering and cell-based therapies. Avoiding central cell necrosis at the centre of large engineered tissue constructs is an important issue for in vitro tissue engineering. Here, the authors demonstrate that this problem may be overcome by oxygenating human mesenchymal stem cells with artificial membrane-binding proteins.