Surface functionalization of inorganic nano-crystals with fibronectin and E-cadherin chimera synergistically accelerates trans-gene delivery into embryonic stem cells
Surface functionalization of inorganic nano-crystals with fibronectin and E-cadherin chimera synergistically accelerates trans-gene delivery into embryonic stem cells
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DOI：
10.1016/j.bbrc.2006.09.081
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发表时间：
2006-11-24
影响因子：
3.1
通讯作者：
Akaike, T.
中科院分区：
文献类型：
--
作者：
Kutsuzawa, K.;Chowdhury, E. H.;Akaike, T.
干细胞在再生医学中有着巨大的前景，有可能通过基因操作分化成特定的细胞类型。然而，传统的基因转移到这种祖细胞的方法存在许多缺点，特别是涉及安全性和有效性问题。在这里，我们报道了通过在载体上嵌入纤维连接蛋白和e -钙粘蛋白嵌合体来开发生物功能化的无机纳米DNA载体，从而使其与胚胎干细胞表面具有高亲和力相互作用，并加速了随后表达的转基因传递。虽然只有磷灰石纳米颗粒转染胚胎干细胞的效率非常低，但纤维连接蛋白锚定颗粒以及纤维连接蛋白和e -cadherin- fc相关颗粒在更大程度上显著增强了转基因传递，其价值明显高于市卖的脂肪转染系统。细胞表面整合素和E-cadherin都参与了介导杂交载体的细胞内定位，通过过量的游离纤维连接蛋白阻断整合素结合位点，并通过PKC激活上调整合素和E-cadherin。因此，新的生物功能杂交基因载体的建立将促进和促进干细胞治疗在再生医学中的发展。(c) 2006爱思唯尔公司版权所有。
Stem cells holding great promises in regenerative medicine have the potential to be differentiated to a specific cell type through genetic manipulation. However, conventional ways of gene transfer to such progenitor cells suffer from a number of disadvantages particularly involving safety and efficacy issues. Here, we report on the development of a bio-functionalized inorganic nano-carrier of DNA by embedding fibronectin and E-cadherin chimera on the carrier, leading to its high affinity interactions with embryonic stem cell surface and accelerated trans-gene delivery for subsequent expression. While only apatite nano-particles were very inefficient in transfecting embryonic stem cells, fibronectin-anchored particles and to a more significant extent, fibronectin and E-cadherin-Fc-associated particles dramatically enhanced trans-gene delivery with a value notably higher than that of commercially available lipofection system. The involvement of both cell surface integrin and E-cadherin in mediating intracellular localization of the hybrid carrier was verified by blocking integrin binding site with excess free fibronectin and up-regulating both integrin and E-cadherin through PKC activation. Thus, the new establishment of a bio-functional hybrid gene-carrier would promote and facilitate development of stem cell-based therapy in regenerative medicine. (c) 2006 Elsevier Inc. All rights reserved.