Student award winner in the undergraduate degree category for the society for biomaterials, 32nd Annual Meeting, Chicago, Illinois, April 17-20, 2007
Student award winner in the undergraduate degree category for the society for biomaterials, 32nd Annual Meeting, Chicago, Illinois, April 17-20, 2007
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DOI：
10.1002/jbm.a.31292
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发表时间：
2007-05-01
影响因子：
4.9
通讯作者：
Anseth, Kristi S.
中科院分区：
文献类型：
--
作者：
Benoit, Danielle S. W.;Tripodi, Margaret C.;Anseth, Kristi S.
用表达整合素连接激酶（ILK）的腺病毒感染人间充质干细胞（hMSCs），以了解细胞- ecm信号转导级联在抑制anoikis中的作用。ilk感染的hMSCs包被聚乙二醇（PEG）水凝胶，在嗜酸诱导的环境中，存活率在7周内维持在90%，存活率归因于蛋白激酶B （PKB/Akt）激活增加。被rgd修饰的水凝胶包裹的hMSCs诱导ILK的产生、PKB/Akt的激活以及随后的存活，其程度与被ILK感染、包裹的hMSCs相同。作为阴性对照，将包封的hMSCs用表达环化重组酶（一种与细胞存活无关的蛋白）的病毒感染，未感染的hMSCs表现出非常少的ILK生成、PKB/Akt激活和存活率（7周后类似于55%）。作为一种细胞-基质相互作用的测量方法，研究人员还对被包膜的hMSCs进行了血管素的定量分析，发现被rgd修饰的水凝胶包膜的细胞比对照组高30倍，被ilk感染的hMSCs高5倍，这表明细胞-物质相互作用正在诱导被rgd修饰的水凝胶包膜的hMSCs的细胞存活能力。总之，ILK感染可以在没有基质相互作用的情况下支持细胞存活，并且可以独立于基质-配体相互作用的情况下，对响应外部信号的三维细胞功能进行基础研究。(c) 2007 Wiley期刊公司
Human mesenchymal stem cells (hMSCs) were infected with an adenovirus expressing integrin-linked kinase (ILK) to understand the role of cell-ECM signal transduction cascades in suppressing anoikis. Survivability of ILK-infected hMSCs encapsulated in poly(ethylene glycol) (PEG) hydrogels, an anoikis-inducing environment, was sustained at 90% over 7 weeks, and survival was attributed to increased protein kinase B (PKB/Akt) activation. hMSCs encapsulated in RGD-modified hydrogels induced an upregulation in ILK production, PKB/Akt activation, and subsequent survival to the same extent of ILK-infected, encapsulated hMSCs. As negative controls, encapsulated hMSCs were infected with cyclization recombinase (a protein not associated with cell survival)-expressing virus, and uninfected hMSCs exhibited very little ILK production, PKB/Akt activation, and survival (similar to 55% after 7 weeks). As a measure of cell-matrix interactions, vinculin was also quantified for the encapsulated hMSCs and found to be 30-fold greater for cells encapsulated in RGD-modified hydrogels and fivefold greater for ILK-infected hMSCs than controls, indicating that cell-material interactions are inducing the cell survivability of hMSCs encapsulated in RGD-modified hydrogels. In sum, ILK infection can support cell survival in the absence of matrix interactions and enable fundamental studies of three-dimensional cell function in response to extrinsic signals, independently of matrix-ligand interactions. (c) 2007 Wiley Periodicals, Inc.