Maturation of induced pluripotent stem cell derived hepatocytes by 3D-culture.
Maturation of induced pluripotent stem cell derived hepatocytes by 3D-culture.
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DOI：
10.1371/journal.pone.0086372
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Vallier L
中科院分区：
文献类型：
--
作者：
Gieseck RL 3rd;Hannan NR;Bort R;Hanley NA;Drake RA;Cameron GW;Wynn TA;Vallier L
诱导多能干细胞衍生肝细胞（IPSC-Heps）有可能减少对从治疗性细胞输注到体外毒理学研究等应用中使用的原代细胞数量减少的需求。然而，目前的分化方案和培养方法产生的细胞与成人肝细胞相比功能和胎儿样特性降低。我们报告了一种使用与高通量筛选相容的三维（3D）胶原基质的IPSC-Heps成熟培养方法。与常规2D系统相比，该培养方法显著增加了IPSC-Heps向成人表型的功能成熟。此外，这种方法自发地导致药物代谢所需的极化结构的存在，并将功能寿命提高到75天以上。总的来说，这项研究揭示了一种将现有IPSC-Heps的表型转移到原代成体肝细胞的方法，使这些细胞成为当前一级标准品的更相关替代品。
Induced pluripotent stem cell derived hepatocytes (IPSC-Heps) have the potential to reduce the demand for a dwindling number of primary cells used in applications ranging from therapeutic cell infusions to in vitro toxicology studies. However, current differentiation protocols and culture methods produce cells with reduced functionality and fetal-like properties compared to adult hepatocytes. We report a culture method for the maturation of IPSC-Heps using 3-Dimensional (3D) collagen matrices compatible with high throughput screening. This culture method significantly increases functional maturation of IPSC-Heps towards an adult phenotype when compared to conventional 2D systems. Additionally, this approach spontaneously results in the presence of polarized structures necessary for drug metabolism and improves functional longevity to over 75 days. Overall, this research reveals a method to shift the phenotype of existing IPSC-Heps towards primary adult hepatocytes allowing such cells to be a more relevant replacement for the current primary standard.
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