Customized hydrogel substrates for serum-free expansion of functional hMSCs.
Customized hydrogel substrates for serum-free expansion of functional hMSCs.
复制标题
用于功能性 hMSC 的无血清扩增的定制水凝胶基质。
DOI：
10.1039/d0bm00540a
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Murphy, William M.
中科院分区：
文献类型：
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作者：
Le, Nhi T;Liu, Leona Tianran;Johnston, James;Krutty, John D;Templeton, Kayla M;Harms, Victoria;Dias, Andrew;Le, Hau;Gopalan, Padma;Murphy, William M.
我们描述了一种筛选方法，以确定定制的无血清人间充质基质细胞（hMSC）培养基板。特别是，我们结合联合收割机的生物材料筛选方法与实验设计（DOE）和多变量分析（MVA），以了解基板刚度，基板粘附性，和媒体组成对hMSC的体外行为的影响。这种方法能够鉴定基于聚（乙二醇）和整合素结合的水凝胶基质组合物，其支持在多种含血清和无血清培养基中的功能性hMSC扩增，以及来自多种不同来源的MSC的扩增。鉴定的底物与标准解冻、接种和收获方案相容。最后，我们在筛选数据上使用MVA来揭示血清和基质硬度对hMSC扩增的重要性，突出了在最佳hMSC生物制造过程中对定制细胞培养基质的需要。
We describe a screening approach to identify customized substrates for serum-free human mesenchymal stromal cell (hMSC) culture. In particular, we combine a biomaterials screening approach with design of experiments (DOE) and multivariate analysis (MVA) to understand the effects of substrate stiffness, substrate adhesivity, and media composition on hMSC behavior in vitro. This approach enabled identification of poly(ethylene glycol)-based and integrin binding hydrogel substrate compositions that supported functional hMSC expansion in multiple serum-containing and serum-free media, as well as the expansion of MSCs from multiple, distinct sources. The identified substrates were compatible with standard thaw, seed, and harvest protocols. Finally, we used MVA on the screening data to reveal the importance of serum and substrate stiffness on hMSC expansion, highlighting the need for customized cell culture substrates in optimal hMSC biomanufacturing processes.