Aggregation of Culture Expanded Human Mesenchymal Stem Cells in Microcarrier-based Bioreactor.
Aggregation of Culture Expanded Human Mesenchymal Stem Cells in Microcarrier-based Bioreactor.
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DOI：
10.1016/j.bej.2017.12.011
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发表时间：
2018-03-15
影响因子：
3.9
通讯作者：
Ma T
中科院分区：
文献类型：
--
作者：
Yuan X;Tsai AC;Farrance I;Rowley J;Ma T
人间充质干细胞（hMSCs）的三维聚集已被用于增强其治疗特性，但目前的制造方案取决于实验室方法，并且不可扩展。在这项研究中，我们开发了热响应聚（N-异丙基丙烯酰胺）接枝微载体（PNIPAM-MCs），它支持在降低的温度（23.0 °C）下的hMSCs的膨胀和热分离。将hMSC在转瓶（SF）和PBS垂直轮（PBS-VW）生物反应器中的PNIPAM-MC上培养用于扩增。在室温下，hMSC作为小细胞片被分离，随后在PBS-VW生物反应器中自组装成3D hMSC聚集体，并且由于不同的流体动力学条件而在SF生物反应器中保持为单细胞。由生物反应器产生的hMSC聚集体与由AggreWell®制备的hMSC聚集体相比保持相当的免疫调节和细胞因子分泌特性。本研究的结果表明，在悬浮生物反应器中使用热响应微载体在封闭的生物反应器系统中进行集成细胞扩增和3D聚集来扩大生产hMSC聚集体的可行性，并突出了流体动力学在悬浮液中分离的hMSC自组装中的关键作用。
Three-dimensional aggregation of human mesenchymal stem cells (hMSCs) has been used to enhance their therapeutic properties but current fabrication protocols depend on laboratory methods and are not scalable. In this study, we developed thermal responsive poly(N-isopropylacrylamide) grafted microcarriers (PNIPAM-MCs), which supported expansion and thermal detachment of hMSCs at reduced temperature (23.0 °C). hMSCs were cultured on the PNIPAM-MCs in both spinner flask (SF) and PBS Vertical-Wheel (PBS-VW) bioreactors for expansion. At room temperature, hMSCs were detached as small cell sheets, which subsequently self-assembled into 3D hMSC aggregates in PBS-VW bioreactor and remain as single cells in SF bioreactor owing to different hydrodynamic conditions. hMSC aggregates generated from the bioreactor maintained comparable immunomodulation and cytokine secretion properties compared to the ones made from the AggreWell®. The results of the current study demonstrate the feasibility of scale-up production of hMSC aggregates in the suspension bioreactor using thermal responsive microcarriers for integrated cell expansion and 3D aggregation in a close bioreactor system and highlight the critical role of hydrodynamics in self-assembly of detached hMSC in suspension.
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影响因子：
3
作者：
Cook, Matthew M.;Futrega, Kathryn;Doran, Michael
通讯作者：
Doran, Michael
影响因子：
2.9
作者：
Kim, Junho;Ma, Teng
通讯作者：
Ma, Teng
影响因子：
3.5
作者：
Ismadi, Mohd-Zulhilmi;Hourigan, Kerry;Fouras, Andreas
通讯作者：
Fouras, Andreas
影响因子：
3.6
作者：
Rettinger, Christina L.;Fourcaudot, Andrea B.;Leung, Kai P.
通讯作者：
Leung, Kai P.
DOI：
10.1039/c0an00609b
发表时间：
2011-02-07
期刊：
The Analyst
影响因子：
--
作者：
Tung YC;Hsiao AY;Allen SG;Torisawa YS;Ho M;Takayama S
通讯作者：
Takayama S