A polyelectrolyte multilayer platform for investigating growth factor delivery modes in human liver cultures.
A polyelectrolyte multilayer platform for investigating growth factor delivery modes in human liver cultures.
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用于研究人类肝脏培养物中生长因子传递模式的聚电解质多层平台。
DOI：
10.1002/jbm.a.36293
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Khetani,SalmanR
中科院分区：
文献类型：
--
作者：
Lin,Christine;Romero,Raimundo;Sorokina,LioudmilaV;Ballinger,KimberlyR;Place,LauraW;Kipper,MattJ;Khetani,SalmanR
Polyelectrolyte multilayers (PEMs) of chitosan and heparin are useful for mimicking growth factor (GF) binding to extracellular matrix (ECM) asin vivo. Here, we developed a PEM platform for delivering bound/adsorbed GFs to monocultures of primary human hepatocytes (PHHs) and PHH/non‐parenchymal cell (NPC) co‐cultures, which are useful for drug development and regenerative medicine. The effects of ECM protein coating (collagen I, fibronectin, and Matrigel®) and terminal PEM layer on PHH attachment/functions were determined. Then, heparin‐terminated/fibronectin‐coated PEMs were used to deliver varying concentrations of an adsorbed model GF, transforming growth factor β (TGFβ), to PHH monocultures while using soluble TGFβ delivery via culture medium as the conventional control. Soluble TGFβ delivery caused a severe, monotonic, and sustained downregulation of all PHH functions measured (albumin and urea secretions, cytochrome‐P450 2A6 and 3A4 enzyme activities), whereas adsorbed TGFβ delivery caused transient upregulation of 3 out of 4 functions. Finally, functionally stable co‐cultures of PHHs and 3T3‐J2 murine embryonic fibroblasts were created on the heparin‐terminated/fibronectin‐coated PEMs modified with adsorbed TGFβ to elucidate similarities and differences in functional response relative to the monocultures. In conclusion, chitosan‐heparin PEMs constitute a robust platform for investigating the effects of GF delivery modes on PHH monocultures and PHH/NPC co‐cultures. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 971–984, 2018.
