Abstract

NK cells have been seen as potential agents in adoptive immunotherapy for cancer. The main challenge for the success of this approach is to obtain a great quantity of activated NK cells for adoptive transfer. The present study had aimed to evaluate the effect of a feeder layer of irradiated MSCs in the in vitro expansion of NK cells. MSCs were obtained from the bone marrow (BM) cells remaining in the bag and filter used in the transplantation of hematopoietic stem cells. NK cells were obtained from peripheral blood (PB) of healthy volunteers. NK expansion and activation were stimulated by culture with artificial antigen-presenting cells (aAPCs) and IL-2, in the presence or absence of BM-MSCs. NK cell proliferation, phenotypic expression and cytotoxic activity were evaluated. Both culture conditions showed high NK purity with predominance of NK CD56^brightCD16⁺ subset post expansion. However, cultures without the presence of MSCs showed higher NK proliferation, expression of activation markers (CD16 and NKG2D) and related cytotoxic activity. In this experimental study, the presence of a feeder layer of irradiated BM-MSCs interfered negatively in the expansion of PB-NKs, limiting their growth and activation. Further investigation is needed to understand the mechanisms of NK-MSC interaction and its implications.

中文翻译：

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在有或没有骨髓间充质干细胞（MSCs）的情况下比较与人工抗原呈递细胞培养的外周血天然杀伤（NK）细胞的实验研究

摘要

NK细胞已被视为过继免疫疗法治疗癌症的潜在药物。这种方法成功的主要挑战是获得大量活化的NK细胞用于过继转移。本研究旨在评估辐照MSCs的饲养层在NK细胞体外扩增中的作用。从袋中剩余的骨髓（BM）细胞和用于造血干细胞移植的滤器中获得MSC。NK细胞获自健康志愿者的外周血（PB）。在存在或不存在BM-MSC的情况下，通过与人工抗原呈递细胞（aAPC）和IL-2的培养刺激NK的扩增和激活。评价NK细胞增殖，表型表达和细胞毒性活性。两种培养条件均显示高NK纯度和NK CD56优势^明亮的CD16 ⁺子集扩增后。但是，不存在MSC的培养物显示出更高的NK增殖，激活标记（CD16和NKG2D）的表达以及相关的细胞毒活性。在这项实验研究中，受辐照的BM-MSC的饲养层的存在对PB-NK的扩增产生了负面影响，从而限制了它们的生长和活化。需要进一步研究以了解NK-MSC相互作用的机制及其含义。