Gornostaeva Aleksandra N, Andreeva Elena R, Bobyleva Polina I, Buravkova Ludmila B
Cell Physiology Laboratory, Institute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye shosse, 76a, Moscow, Russia, 123007.
Cytotechnology. 2018 Feb;70(1):299-312. doi: 10.1007/s10616-017-0144-x. Epub 2017 Oct 3.
Multipotent mesenchymal stem cells (MSCs) are an attractive tool for cell therapy and regenerative medicine. Being applied in vivo, allogeneic MSCs are faced with both activated and unstimulated immune cells. The effects of MSCs on activated immune cells are well described and are mainly suppressive. Less is known about the interaction of MSCs with unstimulated immune cells. We evaluated the contribution of tissue-related O level ("physiological" hypoxia-5% O) and cell-to-cell contact to the interaction between allogeneic adipose tissue-derived MSCs (ASCs) and unstimulated peripheral blood mononuclear cells (PBMCs). Under both O levels, ASCs affected the immune response by elevating the proportion of CD69+ T cells and modifying the functional activity of unstimulated PBMCs, providing a significant reduction of ROS level and activation of lysosome compartment. "Physiological" hypoxia partially attenuated the ASC modulation of PBMC function, reducing CD69+ cell activation and more significantly supressing ROS. In direct co-culture, the ASC effects were more pronounced. PBMC viability was preferentially maintained, and the lymphocyte subset ratio was altered in favour of B cells. Our findings demonstrate that allogeneic ASCs do not enhance the activation of unstimulated immune cells and can provide supportive functions. The "hypoxic" phenotype of ASCs may be more "desirable" for the interaction with allogeneic immune cells that may be required in cell therapy protocols.
多能间充质干细胞（MSCs）是细胞治疗和再生医学中一种具有吸引力的工具。在体内应用时，同种异体MSCs会面临活化和未活化的免疫细胞。MSCs对活化免疫细胞的作用已有充分描述，主要是抑制作用。而关于MSCs与未活化免疫细胞相互作用的了解较少。我们评估了组织相关氧水平（“生理性”低氧——5%氧气）和细胞间接触对同种异体脂肪组织来源的间充质干细胞（ASCs）与未活化外周血单个核细胞（PBMCs）之间相互作用的贡献。在两种氧水平下，ASCs均通过提高CD69+T细胞比例和改变未活化PBMCs的功能活性来影响免疫反应，使活性氧水平显著降低，并激活溶酶体区室。“生理性”低氧部分减弱了ASCs对PBMC功能的调节，减少了CD69+细胞的活化，并更显著地抑制了活性氧。在直接共培养中，ASCs的作用更为明显。优先维持了PBMC的活力，并改变了淋巴细胞亚群比例，有利于B细胞。我们的研究结果表明，同种异体ASCs不会增强未活化免疫细胞的活化，而是可以提供支持性功能。ASCs的“低氧”表型对于细胞治疗方案中可能需要的与同种异体免疫细胞的相互作用可能更“理想”。
