Viral infection of human progenitor and liver-derived cells encapsulated in three-dimensional PEG-based hydrogel

Viral infection of human progenitor and liver-derived cells encapsulated in three-dimensional PEG-based hydrogel
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DOI:
10.1088/1748-6041/25/1/011001
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发表时间:
2009-02-01
影响因子:
4
通讯作者:
Glenn, Jeffrey S.
Glenn, Jeffrey S.
中科院分区:
工程技术3区
文献类型:
--
作者:
Cho, Nam-Joon;Elazar, Menashe;Glenn, Jeffrey S.

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我们已经研究了将人祖细胞包封到3D PEG水凝胶中。无复制能力的慢病毒启动子报告载体被发现可以有效地检测水凝胶包封的肝祖细胞中人肝基因的体内表达。类似地,水凝胶包封的细胞可以有效地感染丙型肝炎病毒,并且可以从水凝胶的培养基上清液中回收子代感染性病毒。具有挑衅性的是,这些病毒颗粒的直径范围从近似50至100 nm,而计算的8 k水凝胶的筛孔尺寸为44.6 +/-1.7埃。为了调和病毒颗粒如何穿透水凝胶感染封装的细胞,我们建议水凝胶的微裂缝/缺陷导致的功能孔径比理论网格计算预测的大20倍。这些结果提示了一种新的水凝胶结构模型,并对组织工程和肝炎病毒研究具有令人兴奋的意义。
We have studied the encapsulation of human progenitor cells into 3D PEG hydrogels. Replication-incompetent lentivirus promoter reporter vectors were found to efficiently detect the in vivo expression of human hepatic genes in hydrogel-encapsulated liver progenitor cells. Similarly, hydrogel-encapsulated cells could be efficiently infected with hepatitis C virus, and progeny infectious virus could be recovered from the media supernatants of the hydrogels. Provocatively, the diameters of these virus particles range from similar to 50 to 100 nm, while the calculated mesh size of the 8 k hydrogel is 44.6 +/- 1.7 angstrom. To reconcile how viral particles can penetrate the hydrogels to infect the encapsulated cells, we propose that microfractures/defects of the hydrogel result in a functional pore size of up to 20 fold greater than predicted by theoretical mesh calculations. These results suggest a new model of hydrogel structure, and have exciting implications for tissue engineering and hepatitis virus studies.