Microfluidics-assisted fabrication of natural killer cell-laden microgel enhances the therapeutic efficacy for tumor immunotherapy

被引:1
作者
Lee, Dongjin [1 ,2 ]
Kim, Seok Min
Kim, Dahong [2 ,4 ]
Baek, Seung Yeop [5 ]
Yeo, Seon Ju [2 ]
Lee, Jae Jong [2 ]
Cha, Chaenyung [5 ,6 ]
Park, Su A. [2 ]
Kim, Tae-Don [1 ,3 ]
机构
[1] Korea Res Inst Biosci & Biotechnol KRIBB, Immunotherapy Convergence Res Ctr, Daejeon 34141, South Korea
[2] Korea Inst Machinery & Mat KIMM, Nanoconvergence Mfg Res Div, Daejeon 34103, South Korea
[3] Korea Univ Sci & Technol UST, KRIBB Sch Biosci, Dept Funct Genom, Daejeon 34113, South Korea
[4] Seoul Natl Univ, Dept Appl Bioengn, Seoul 08826, South Korea
[5] Ulsan Natl Inst Sci & Technol, Sch Mat Sci & Engn, Ulsan 44919, South Korea
[6] Ulsan Natl Inst Sci & Technol, Sch Life Sci, Dept Biomed Engn, Ulsan 44919, South Korea
基金
新加坡国家研究基金会;
关键词
Double flow -focusing microfluidics; NK92 cell encapsulation; Microgel mechanics; Microgel degradation; Cancer immunotherapy; GELATIN; HYDROGEL; CULTURE; NK; MICROSPHERES; ACTIVATION; MECHANISMS;
D O I
10.1016/j.mtbio.2024.101055
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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 twodimensional (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.
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页数:11
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