Lee Dongjin, Kim Seok Min, Kim Dahong, Baek Seung Yeop, Yeo Seon Ju, Lee Jae Jong, Cha Chaenyung, Park Su A, Kim Tae-Don
Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
Nano-Convergence Manufacturing Research Division, Korea Institute of Machinery and Materials (KIMM), Daejeon, 34103, Republic of Korea.
Mater Today Bio. 2024 Apr 17;26:101055. doi: 10.1016/j.mtbio.2024.101055. eCollection 2024 Jun.
Recently, interest in cancer immunotherapy has increased over traditional anti-cancer therapies such as chemotherapy or targeted therapy. Natural killer (NK) cells are part of the immune cell family and essential to tumor immunotherapy as they detect and kill cancer cells. However, the disadvantage of NK cells is that cell culture is difficult. In this study, porous microgels have been fabricated using microfluidic channels to effectively culture NK cells. Microgel fabrication using microfluidics can be mass-produced in a short time and can be made in a uniform size. Microgels consist of photo cross-linkable polymers such as methacrylic gelatin (GelMa) and can be regulated via controlled GelMa concentrations. NK92 cell-laden three-dimensional (3D) microgels increase mRNA expression levels, NK92 cell proliferation, cytokine release, and anti-tumor efficacy, compared with two-dimensional (2D) cultures. In addition, the study confirms that 3D-cultured NK92 cells enhance anti-tumor effects compared with enhancement by 2D-cultured NK92 cells in the K562 leukemia mouse model. Microgels containing healthy NK cells are designed to completely degrade after 5 days allowing NK cells to be released to achieve cell-to-cell interaction with cancer cells. Overall, this microgel system provides a new cell culture platform for the effective culturing of NK cells and a new strategy for developing immune cell therapy.
最近,相较于化疗或靶向治疗等传统抗癌疗法,癌症免疫疗法受到了更多关注。自然杀伤(NK)细胞是免疫细胞家族的一部分,对肿瘤免疫疗法至关重要,因为它们能够检测并杀死癌细胞。然而,NK细胞的缺点是细胞培养困难。在本研究中,利用微流控通道制备了多孔微凝胶,以有效培养NK细胞。使用微流控技术制备微凝胶能够在短时间内大量生产,且尺寸均匀。微凝胶由甲基丙烯酸明胶(GelMa)等可光交联聚合物组成,可通过控制GelMa浓度进行调控。与二维(2D)培养相比,负载NK92细胞的三维(3D)微凝胶可提高mRNA表达水平、NK92细胞增殖、细胞因子释放及抗肿瘤功效。此外,该研究证实,在K562白血病小鼠模型中,与二维培养的NK92细胞增强的抗肿瘤效果相比,三维培养的NK92细胞具有更强的抗肿瘤作用。含有健康NK细胞的微凝胶设计为在5天后完全降解,使NK细胞得以释放,从而实现与癌细胞的细胞间相互作用。总体而言,这种微凝胶系统为有效培养NK细胞提供了一个新的细胞培养平台,并为开发免疫细胞疗法提供了一种新策略。