Abdulaziz Almutairi, Najlaa A Alshehri, Abdullah Al Subayyil, Eman Bahattab, Manal Alshabibi, Fawaz Abomaray, Yasser S Basmaeil, Tanvir Khatlani
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引用次数: 0
Abstract
Introduction: Mesenchymal stem cells/stromal cells from the Decidua Basalis of the human placenta (DBMSCs) express wide range of effector molecules that modulate the functions of their target cells. These properties make them potential candidate for use in cellular therapy. In this study, we have investigated the consequences of interaction between DBMSCs and natural killer (NK) cells for both cell types.
Methods: DBMSCs were cultured with IL-2-activated and resting non-activated NK cells isolated from healthy human peripheral blood and various functional assays were performed including, NK cell proliferation and cytolytic activities. Flow cytometry and microscopic studies were performed to examine the expression of NK cell receptors that mediate these cytolytic activities against DBMSCs. Moreover, the mechanism underlying these effects was also investigated.
Results: Our findings revealed that, co-culture of DBMSCs and NK cells resulted in inhibition of proliferation of resting NK cells, while proliferation of IL-2 activated NK cells was increased. Contrarily, treatment of DBMSC's with comparatively high numbers of IL-2 activated NK cells, resulted in their lysis, whereas treatment with low numbers resulted in reduction in their proliferation. Cytolytic activity of NK cells against DBMSCs was mediated by several activating NK cell receptors. In spite of the expression of HLA class I molecules by DBMSCs, they were still lysed by NK cells, excluding their involvement in cytolytic activity. In addition, preconditioning NK cells by DBMSCs, enhanced their ability to suppress tumor cell proliferation and in severe cases resulted in their partial lysis. Lysis and decrease of tumor cell proliferation is associated with increased expression of important molecules involved in anticancer activities.
Discussion: We conclude that DBMSCs exhibit dualfunctions on NK cells that enhance their anticancer therapeutic potential.
简介来自人类胎盘蜕膜基底层的间充质干细胞/基质细胞（DBMSCs）表达多种效应分子，可调节其靶细胞的功能。这些特性使它们成为细胞疗法的潜在候选者。在这项研究中，我们调查了DBMSCs和自然杀伤（NK）细胞之间的相互作用对两种细胞类型的影响：方法：将 DBMSCs 与从健康人外周血中分离的 IL-2 激活型和静息非激活型 NK 细胞一起培养，并进行各种功能测试，包括 NK 细胞增殖和细胞溶解活性。还进行了流式细胞术和显微镜研究，以检测介导这些针对 DBMSCs 的细胞溶解活性的 NK 细胞受体的表达。此外，还研究了这些效应的机制：我们的研究结果表明，DBMSCs 和 NK 细胞的共培养抑制了静止 NK 细胞的增殖，而 IL-2 激活的 NK 细胞的增殖却增加了。相反，用相对较多的 IL-2 活化 NK 细胞处理 DBMSC，会导致其溶解，而用较少的 IL-2 活化 NK 细胞处理，则会导致其增殖减少。NK 细胞对 DBMSCs 的细胞溶解活性由几种活化 NK 细胞受体介导。尽管 DBMSCs 表达 HLA I 类分子，但仍被 NK 细胞裂解，这排除了它们参与细胞溶解活性的可能性。此外，用 DBMSCs 预处理 NK 细胞可增强其抑制肿瘤细胞增殖的能力，严重时还会导致肿瘤细胞部分裂解。肿瘤细胞的溶解和增殖减少与参与抗癌活动的重要分子的表达增加有关：我们的结论是，DBMSCs 对 NK 细胞具有双重功能，可增强其抗癌治疗潜力。
期刊介绍：
Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board.
The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology.
With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.
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