A robust potency assay highlights significant donor variation of human mesenchymal stem/progenitor cell immune modulatory capacity and extended radio-resistance.
A robust potency assay highlights significant donor variation of human mesenchymal stem/progenitor cell immune modulatory capacity and extended radio-resistance.
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DOI：
10.1186/s13287-015-0233-8
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发表时间：
2015-12-01
影响因子：
7.5
通讯作者：
Strunk D
中科院分区：
文献类型：
--
作者：
Ketterl N;Brachtl G;Schuh C;Bieback K;Schallmoser K;Reinisch A;Strunk D
间充质干/祖细胞（MSPCs）固有的免疫调节能力鼓励启动多个临床试验。治疗性MSPC的放行标准涵盖同一性、纯度和安全性，但通常缺少适当的效价评估。关于MSPC功能异质性的报告在供体和器官/来源选择方面产生了额外的不确定性。我们建立了一个强大的免疫调节效力试验的基础上合并应答者白细胞，以尽量减少个体免疫应答的变异性。比较各种MSPC显示出显著的效力不一致性，并且与有丝分裂发生的剂量依赖性抑制相比，同种异体免疫抑制通常减少。伽马辐照阻断非预期MSPC增殖并没有抑制体内软骨形成和骨形成，表明需要替代安全策略。本文的在线版本（doi：10.1186/s13287-015-0233-8）包含补充材料，可供授权用户使用。
The inherent immunomodulatory capacity of mesenchymal stem/progenitor cells (MSPCs) encouraged initiation of multiple clinical trials. Release criteria for therapeutic MSPCs cover identity, purity and safety but appropriate potency assessment is often missing. Reports on functional heterogeneity of MSPCs created additional uncertainty regarding donor and organ/source selection. We established a robust immunomodulation potency assay based on pooling responder leukocytes to minimize individual immune response variability. Comparing various MSPCs revealed significant potency inconsistency and generally diminished allo-immunosuppression compared to dose-dependent inhibition of mitogenesis. Gamma-irradiation to block unintended MSPC proliferation did not prohibit chondrogenesis and osteogenesis in vivo, indicating the need for alternative safety strategies. The online version of this article (doi:10.1186/s13287-015-0233-8) contains supplementary material, which is available to authorized users.