Department of Chemical & Biochemical Engineering, Dongguk University, Seoul 22012, Republic of Korea.
Int J Mol Sci. 2024 Jan 26;25(3):1556. doi: 10.3390/ijms25031556.
Current cytokine-based natural killer (NK) cell priming techniques have exhibited limitations such as the deactivation of biological signaling molecules and subsequent insufficient maturation of the cell population during mass cultivation processes. In this study, we developed an amphiphilic trigonal 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-polyethylene glycol (PEG) material to assemble NK cell clusters via multiple hydrophobic lipid insertions into cellular membranes. Our lipid conjugate-mediated ex vivo NK cell priming sufficiently augmented the structural modulation of clusters, facilitated diffusional signal exchanges, and finally activated NK cell population with the clusters. Without any inhibition in diffusional signal exchanges and intrinsic proliferative efficacy of NK cells, effectively prime NK cell clusters produced increased interferon-gamma, especially in the early culture periods. In conclusion, the present study demonstrates that our novel lipid conjugates could serve as a promising alternative for future NK cell mass production.
目前基于细胞因子的自然杀伤 (NK) 细胞的初始激活技术存在一些局限性,例如在大规模培养过程中生物信号分子失活,以及随后细胞群体的成熟不足。在本研究中,我们开发了一种两亲性三角 1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺 (DSPE) 脂质-聚乙二醇 (PEG) 材料,通过将多个疏水性脂质插入细胞膜来组装 NK 细胞簇。我们的脂联体介导的 NK 细胞的体外初始激活充分增强了细胞簇的结构调节,促进了扩散信号交换,最终使具有细胞簇的 NK 细胞群体被激活。在不抑制扩散信号交换和 NK 细胞内在增殖效力的情况下,有效地初始激活 NK 细胞簇可产生更多的干扰素-γ,尤其是在早期培养阶段。总之,本研究表明,我们的新型脂质偶联物可能成为未来 NK 细胞大规模生产的一种有前途的替代方法。