Derivation of clinical -grade mesenchymal stromal cells from umbilical cord under chemically de fined culture condition-platform for future clinical application
Derivation of clinical -grade mesenchymal stromal cells from umbilical cord under chemically de fined culture condition-platform for future clinical application
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DOI：
10.1016/j.jcyt.2020.03.431
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发表时间：
2020-07-01
期刊：
影响因子：
4.5
通讯作者：
Wu, Daocheng
中科院分区：
文献类型：
--
作者：
Wu, Xiaoyun;Ma, Zhijie;Wu, Daocheng
在培养基中使用动物血清会带来安全问题和批次间差异，因此可能限制离体扩增间充质基质细胞（MSC）的临床使用。临床上符合要求的 MSC 应当遵循无血清、无异源和化学成分确定的培养基 (S&XFM-CD) 进行开发。在这项研究中，我们通过用合成替代品替换所有血清成分来开发 S&XFM-CD，以衍生临床级脐带源间充质干细胞 (UCMSC)。将 S&XFM-CD 中 UCMSC 的特性、安全性、效力和外源因素污染风险等关键方面与含血清培养基 (SCM) 进行比较。 S&XFM-CD中的UCMSC保留了MSC的成纤维细胞样形态和免疫表型，并且与SCM相比表现出优异的克隆效率、增殖能力以及成骨和软骨形成潜力。此外，与 SCM 相比，S&XFM-CD 中的 UCMSC 保留了相似的免疫抑制潜力，并且表现出更高的 bFGF、PDGF-BB 和 IGF-1 分泌水平。此外，S&XFM-CD中的UCMSC不发生转化，保留了正常的核型和基因组稳定性，并且在体外长期培养后不易发生衰老过程，符合现行国际和国家评价标准的指导。这里开发的S&XFM-CD可以作为UCMSCs的GMP级生产平台，用于未来的临床应用。 ？ 2020 年国际细胞和基因治疗学会。由爱思唯尔公司出版。保留所有权利。
The use of animal serum in culture medium brings safety concerns and batch -to -batch variability, and thus may restrict the clinical use of ex vivo expanded mesenchymal stromal cells (MSCs). Clinically compliant MSCs should be developed in adherence to serum -free, xeno-free and chemically de fined medium (S&XFM-CD). In this study, we develop a S&XFM-CD by replacing all serum components with synthetic alternatives for the deri- vation of clinical -grade umbilical cord -derived MSCs (UCMSCs). The critical aspects including characterization, safety concerns, potency and exogenous factors contamination risk of UCMSCs in S&XFM-CD are compared with serum -containing medium (SCM). UCMSCs in S&XFM-CD retain fibroblastic -like morphology and immu- nophenotype of MSCs, and exhibit superior clone ef ficiency, proliferation capacity, and osteogenic and chon- drogenic differentiation potential compared with SCM. Moreover, UCMSCs in S&XFM-CD retain similar immunosuppressive potential, and exhibit superior secretion levels of bFGF, PDGF-BB and IGF-1 compared with SCM. In addition, UCMSCs in S&XFM-CD do not undergo transformation, preserve the normal karyotypes and genomic stability, and are less prone to senescence process after long-term in vitro culture, which con- forms to the current guidance of international and national evaluation standard. The S&XFM-CD developed here may serve as a GMP-grade production platform of UCMSCs for future clinical application. ? 2020 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.