Umbilical cord tissue-derived mesenchymal stromal cells maintain immunomodulatory and angiogenic potencies after cryopreservation and subsequent thawing
Umbilical cord tissue-derived mesenchymal stromal cells maintain immunomodulatory and angiogenic potencies after cryopreservation and subsequent thawing
复制标题
DOI：
10.1016/j.jcyt.2016.11.008
复制
发表时间：
2017-03-01
期刊：
影响因子：
4.5
通讯作者：
Cruz, Helder
中科院分区：
文献类型：
--
作者：
Barcia, Rita N.;Santos, Jorge M.;Cruz, Helder
背景目标。冷冻保存对间充质基质细胞（MSC）治疗特性的影响已成为高度争议的问题。然而，迄今为止的数据不加区别地涉及对具有不同生产过程的不同类型的MSC的评估。这项研究假设基于MSC的产品受到不同的影响，这取决于组织来源和制造过程，并分析了冷冻保存对脐带组织来源的MSC（UC-MSC），UCX（R）的特定群体的影响。方法.通过流式细胞术通过评价相关表面标志物如CD 14、CD 19、CD 31、CD 34、CD 44、CD 45、CD 90、CD 105、CD 146、CD 200、CD 273、CD 274和HLA-免疫调节活性在体外通过抑制活化T细胞的能力进行分析，在体内通过逆转信号的能力进行分析。炎症在一个促炎剂诱导的关节炎（AIA）模型。使用基于人脐静脉内皮细胞的血管生成测定法在体外评价血管生成潜力，并使用小鼠后肢缺血模型在体内评价血管生成潜力。结果表型和免疫调节和血管生成的能力，这一特定的UC-MSC人口没有受到损害的冷冻保存和随后的解冻，在体外和体内。讨论本研究表明，生产工艺可以避免与给定组织来源中的冷冻保存相关的效价受损。研究结果对开发先进的治疗药物产品具有积极意义。
Background aims. The effect of cryopreservation on mesenchymal stromal cell (MSC) therapeutic properties has become highly controversial. However, data thus far have indiscriminately involved the assessment of different types of MSCs with distinct production processes. This study assumed that MSC-based products are affected differently depending on the tissue source and manufacturing process and analyzed the effect of cryopreservation on a specific population of umbilical cord tissue derived MSCs (UC-MSCs), UCX (R). Methods. Cell phenotype was assessed by flow cytometry through the evaluation of the expression of relevant surface markers such as CD14, CD19, CD31, CD34, CD44, CD45, CD90, CD105, CD146, CD200, CD273, CD274 and HLA-DR. Immunomodulatory activity was analyzed in vitro through the ability to inhibit activated T cells and in vivo by the ability to reverse the signs of inflammation in an adjuvant-induced arthritis (AIA) model. Angiogenic potential was evaluated in vitro using a human umbilical vein endothelial cell based angiogenesis assay, and in vivo using a mouse model for hindlimb ischemia. Results. Phenotype and immunomodulatory and angiogenic potencies of this specific UC-MSC population were not impaired by cryopreservation and subsequent thawing, both in vitro and in vivo. Discussion. This study suggests that potency impairment related to cryopreservation in a given tissue source can be avoided by the production process. The results have positive implications for the development of advanced-therapy medicinal products.