Challenges in cryopreservation of regulatory T cells (Tregs) for clinical therapeutic applications
Challenges in cryopreservation of regulatory T cells (Tregs) for clinical therapeutic applications
复制标题
DOI：
10.1016/j.intimp.2013.02.001
复制
发表时间：
2013-07-01
影响因子：
5.6
通讯作者：
Witkowski, Piotr
中科院分区：
文献类型：
--
作者：
Golab, Karolina;Leveson-Gower, Dennis;Witkowski, Piotr
将体外扩增的调节性T细胞（Treg）作为一种临床干预手段的初步研究取得了有前景的结果，这增加了人们对这种细胞疗法的兴趣，并且目前有几项涉及Treg的新临床试验正在进行中。Treg的分离和扩增方法已经过研究和优化，达到了这种疗法可行的程度，并能按照药品生产质量管理规范（GMP）指南在实验室中获得足够数量的Treg。然而，如果Treg能够被有效地冷冻保存并储存用于未来的输注或扩增，而不是像现在这样只使用新鲜分离和扩增的细胞，Treg疗法可能会发展得更快。目前，我们关于冷冻保存对Treg恢复、活力和功能影响的了解仍然有限。根据冷冻保存外周血单个核细胞（PBMC）的经验，冷冻保存可能对Treg有有害影响，会降低Treg的活力，导致细胞因子异常分泌，并损害对Treg正常功能和处理至关重要的表面标志物的表达。因此，用于临床应用的Treg冷冻保存以及细胞培养、扩增和处理的最佳策略和条件仍需研究和确定。（C）2013爱思唯尔公司。保留所有权利。
Promising results of initial studies applying ex-vivo expanded regulatory T cell (Treg) as a clinical intervention have increased interest in this type of the cellular therapy and several new clinical trials involving Tregs are currently on the way. Methods of isolation and expansion of Tregs have been studied and optimized to the extent that such therapy is feasible, and allows obtaining sufficient numbers of Tregs in the laboratory following Good Manufacturing Practice (GMP) guidelines. Nevertheless, Treg therapy could even more rapidly evolve if Tregs could be efficiently cryopreserved and stored for future infusion or expansions rather than utilization of only freshly isolated and expanded cells as it is preferred now. Currently, our knowledge regarding the impact of cryopreservation on Treg recovery, viability, and functionality is still limited. Based on experience with cryopreserved peripheral blood mononuclear cells (PBMCs), cryopreservation may have a detrimental effect on Tregs, can decrease Treg viability, cause abnormal cytokine secretion, and compromise expression of surface markers essential for proper Treg function and processing. Therefore, optimal strategies and conditions for Treg cryopreservation in conjunction with cell culture, expansion, and processing for clinical application still need to be investigated and defined. (C) 2013 Elsevier B.V. All rights reserved.