Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function.
Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function.
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DOI：
10.1016/j.biomaterials.2012.03.034
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发表时间：
2012-06
期刊：
影响因子：
14
通讯作者：
Zhang, Yuanyuan
中科院分区：
文献类型：
--
作者：
Skardal, Aleksander;Smith, Leona;Bharadwaj, Shantaram;Atala, Anthony;Soker, Shay;Zhang, Yuanyuan
尽管最近在生物材料科学方面取得了进展，但还没有支持人成年肝细胞长期培养扩增同时保持持续功能的培养系统。以往的研究表明，脱细胞肝细胞外基质（ECM），作为一种底物，促进肝细胞的增殖和功能。在这里，我们研究了从脱细胞肝ECM（肝ECM提取物，LEE）或从整个（新鲜）肝组织（肝组织提取物，LTE）制备的提取物是否可以与I型胶原、透明质酸（HA）或肝素缀合的HA（HP）水凝胶组合以增强原代人肝细胞的存活和功能输出。通过将LEE或LTE掺入凝胶基质中来制备肝脏特异性半合成ECM（sECM）。随后，将原代人肝细胞在培养型水凝胶培养物中维持4周。在所有HA和HP组中均观察到肝细胞代谢进行性增加。在含有LEE或LTE的HA和HP水凝胶中培养的肝细胞合成并分泌稳定水平的白蛋白和尿素以及持续的细胞色素p450依赖的乙氧基香豆素药物代谢。总的来说，这些结果表明，具有肝脏特异性ECM组分的定制HA水凝胶可能是用于体外扩增人肝细胞以用于细胞治疗以及药物和毒理学筛选目的的有效方法。
Despite recent advances in biomaterial science, there is yet no culture system that supports long-term culture expansion of human adult hepatocytes, while preserving continued function. Previous studies suggested that acellular liver extracellular matrix (ECM), employed as a substrate, improved proliferation and function of liver cells. Here we investigated whether extracts prepared from acellular liver ECM (liver ECM extract, LEE), or from whole (fresh) liver tissue (liver tissue extract, LTE), could be combined with collagen Type I, hyaluronic acid (HA), or heparin-conjugated HA (HP) hydrogels to enhance survival and functional output of primary human hepatocytes. The liver-specific semi-synthetic ECMs (sECMs) were prepared by incorporating LEE or LTE into the gel matrices. Subsequently, primary human hepatocytes were maintained in sandwich-style hydrogel cultures for 4 weeks. Progressive increase in hepatocyte metabolism was observed in all HA and HP groups. Hepatocytes cultured in HA and HP hydrogels containing LEE or LTE synthesized and secreted steady levels of albumin and urea and sustained cytochrome p450-dependent drug metabolism of ethoxycoumarin. Collectively, these results indicate that customized HA hydrogels with liver-specific ECM components may be an efficient method for expansion human hepatocytes in vitro for cell therapy and drug and toxicology screening purposes.
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原代肝细胞培养用壳聚糖/半乳糖化透明质酸支架的制备及表征
DOI：
10.1007/s10856-009-3833-y
发表时间：
2010-01-01
影响因子：
3.7
作者：
Fan, Jinyong;Shang, Yi;Yang, Jun
通讯作者：
Yang, Jun
影响因子：
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作者：
Skardal, Aleksander;Zhang, Jianxing;Prestwich, Glenn D.
通讯作者：
Prestwich, Glenn D.
影响因子：
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作者：
Williams, Courtney M.;Mehta, Geeta;Griffith, Linda G.
通讯作者：
Griffith, Linda G.
影响因子：
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作者：
Serban, Monica A;Scott, Anna;Prestwich, Glenn D
通讯作者：
Prestwich, Glenn D
影响因子：
14
作者：
Freytes, Donald O.;Martin, Jeffrey;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.