Dymowska Marta, Aksamit Aleksandra, Zielniok Katarzyna, Kniotek Monika, Kaleta Beata, Roszczyk Aleksander, Zych Michal, Dabrowski Filip, Paczek Leszek, Burdzinska Anna
Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Poland.
Laboratory of Cell Research and Application, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
Pharmaceutics. 2021 Nov 1;13(11):1822. doi: 10.3390/pharmaceutics13111822.
Despite intensive clinical research on the use of mesenchymal stromal cells (MSCs), further basic research in this field is still required. Herein, we compared human bone marrow MSCs (BM-MSCs, = 6) and Wharton's jelly MSCs (WJ-MSCs, = 6) in their ability to interact with human primary macrophages. Evaluation of secretory potential revealed that under pro-inflammatory stimulation, WJ-MSCs secreted significantly more IL-6 than BM-MSCs (2-fold). This difference did not translate into the effect of MSCs on macrophages: both types of MSCs significantly directed M1-like macrophages toward the M2 phenotype (based on CD206 expression) to a similar extent. This observation was consistent both in flow cytometry analysis and immunocytochemical assessment. The effect of MSCs on macrophages was sustained when IL-6 signaling was blocked with Tocilizumab. Macrophages, regardless of polarization status, enhanced chemotaxis of both BM-MSCs and WJ-MSCs ( < 0.01; trans-well assay), with WJ-MSCs being significantly more responsive to M1-derived chemotactic signals than BM-MSCs. Furthermore, WJ-MSCs increased their motility (scratch assay) when exposed to macrophage-conditioned medium while BM-MSCs did not. These results indicate that although both BM-MSCs and WJ-MSCs have the ability to reciprocally interact with macrophages, the source of MSCs could slightly but significantly modify the response under clinical settings.
尽管对间充质基质细胞(MSCs)的使用进行了深入的临床研究,但该领域仍需要进一步的基础研究。在此,我们比较了人骨髓间充质干细胞(BM-MSCs,n = 6)和沃顿胶间充质干细胞(WJ-MSCs,n = 6)与人类原代巨噬细胞相互作用的能力。分泌潜能评估显示,在促炎刺激下,WJ-MSCs分泌的IL-6明显多于BM-MSCs(2倍)。但这种差异并未转化为间充质干细胞对巨噬细胞的影响:两种类型的间充质干细胞都能在相似程度上显著地将M1样巨噬细胞导向M2表型(基于CD206表达)。这一观察结果在流式细胞术分析和免疫细胞化学评估中均一致。当用托珠单抗阻断IL-6信号时,间充质干细胞对巨噬细胞的影响得以持续。无论极化状态如何,巨噬细胞均增强了BM-MSCs和WJ-MSCs的趋化性(P < 0.01;Transwell分析),其中WJ-MSCs对M1衍生的趋化信号的反应明显强于BM-MSCs。此外,当暴露于巨噬细胞条件培养基时,WJ-MSCs的运动能力增强(划痕试验),而BM-MSCs则没有。这些结果表明,尽管BM-MSCs和WJ-MSCs都有能力与巨噬细胞相互作用,但在临床环境下,间充质干细胞的来源可能会轻微但显著地改变反应。