DNA delivery from matrix metalloproteinase degradable poly(ethylene glycol) hydrogels to mouse cloned mesenchymal stem cells.
DNA delivery from matrix metalloproteinase degradable poly(ethylene glycol) hydrogels to mouse cloned mesenchymal stem cells.
复制标题
DOI：
10.1016/j.biomaterials.2008.09.027
复制
发表时间：
2009-01
期刊：
影响因子：
14
通讯作者：
Segura, Tatiana
中科院分区：
文献类型：
--
作者：
Lei, Yuguo;Segura, Tatiana
将间充质干细胞（MSC）接种在合成水凝胶支架内进行遗传修饰的能力将提供一种替代方法来引导MSC分化，并在三维中研究分子通路，而不是蛋白质递送。在这份报告中，我们探讨了基因转移到浸润骨髓间充质干细胞基质金属蛋白酶（MMP）可降解的水凝胶，载有DNA/聚（乙烯亚胺）（PEI）聚合物。DNA/PEI复合物被封装在聚（乙二醇）（PEG）水凝胶内，通过迈克尔加成化学与MMP可降解肽交联。大部分封装的复合物在封装后仍保持活性（65%），并且水凝胶的机械性质未被复合物的封装改变。使用两种不同的方法将细胞接种在水凝胶支架内，成簇和均质。MSC的活力在具有和不具有复合物的水凝胶中是相似的。转基因表达的特点是随着时间的推移，使用分泌的报告基因，并表现出不同的配置文件为集群和均匀接种的细胞。接种的细胞导致累积转基因表达增加，通过21天的孵育，而均匀接种的细胞导致累积转基因表达，在培养7天后达到平台。使用允许细胞浸润以递送DNA的水凝胶支架可以在体内产生持久的信号，这对于功能组织的再生是必不可少的。
The ability to genetically modify mesenchymal stem cells (MSCs) seeded inside synthetic hydrogel scaffolds would offer an alternative approach to guide MSC differentiation and to study molecular pathways in three dimensions than protein delivery. In this report, we explored gene transfer to infiltrating MSCs into matrix metalloproteinase (MMP) degradable hydrogels that were loaded with DNA/poly(ethylene imine) (PEI) polyplexes. DNA/PEI polyplexes were encapsulated inside poly(ethylene glycol) (PEG) hydrogels crosslinked with MMP degradable peptides via Michael Addition chemistry. A large fraction of encapsulated polyplexes remained active after encapsulation (65%) and the mechanical properties of the hydrogels were unchanged by the encapsulation of the polyplexes. Cells were seeded inside the hydrogel scaffolds using two different approaches, clustered and homogeneous. The viability of MSCs was similar in hydrogels with and without polyplexes. Transgene expression was characterized with time using a secreted reporter gene and showed different profiles for clustered and homogeneously seeded cells. Clustered cells resulted in cumulative transgene expression that increased through the 21-day incubation, while homogeneously seeded cells resulted in cumulative transgene expression that plateaued after 7-days of culture. The use of hydrogel scaffolds that allow cellular infiltration to deliver DNA may result in long lasting signals in vivo, which are essential for the regeneration of functional tissues.
登录
查看更多内容
影响因子：
3.8
作者：
Adami, RC;Collard, WT;Rice, KG
通讯作者：
Rice, KG
影响因子：
5.1
作者：
Aoki, K;Furuhata, S;Yoshida, T
通讯作者：
Yoshida, T
影响因子：
12.4
作者：
Gautam, A;Densmore, CL;Waldrep, JC
通讯作者：
Waldrep, JC
影响因子：
82.9
作者：
Bonadio, J;Smiley, E;Goldstein, S
通讯作者：
Goldstein, S
影响因子：
6.2
作者：
Lutolf, MP;Hubbell, JA
通讯作者：
Hubbell, JA