Engineering microscale cellular niches for three-dimensional multicellular co-cultures

被引:298
作者
Huang, Carlos P. [2 ]
Lu, Jente [2 ]
Seon, Hyeryung [3 ]
Lee, Abraham P. [2 ]
Flanagan, Lisa A. [4 ]
Kim, Ho-Young [1 ]
Putnam, Andrew J. [2 ,3 ]
Jeon, Noo Li [1 ]
机构
[1] Seoul Natl Univ, Sch Mech & Aerosp Engn, Seoul 151744, South Korea
[2] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA
[3] Univ Calif Irvine, Dept Chem Engn & Mat Sci, Irvine, CA 92697 USA
[4] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA
基金
美国国家卫生研究院;
关键词
MICROFLUIDIC PLATFORM; STEM-CELLS; 3D; MATRIX; SCAFFOLDS; CULTURE; MICROENVIRONMENTS; MORPHOGENESIS; ENVIRONMENTS; GENERATION;
D O I
10.1039/b818401a
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Modeling the in vivo microenvironment typically involves placing cells in a three-dimensional (3D) extracellular matrix (ECM) in physiologically relevant context with respect to other cells. The mechanical and chemical features of 3D microenvironments play important roles in tissue engineering, tumor growth and metastasis, and in defining stem cell niches, and it is increasingly recognized that cells behave much differently when surrounded by a 3D ECM than when anchored to a 2D substrate. To create microenvironments that more closely mimic in vivo settings, here we describe a novel microfluidic device that allows multiple discrete constructs of 3D cell-laden hydrogels to be patterned in a sequence of simple steps. The microfluidic platform allows for real-time imaging of the interactions between multiple cell types exposed to both autocrine and paracrine signaling molecules, all within a 3D ECM environment. Detailed modeling determined that surface tension, hydrophobic interactions, and spatial geometry were important factors in containing the gels within distinct separate channels during the filling process. This allowed us to pattern multiple gel types side-by-side and pattern 3D gels spatially with tight dimensional control. Cells embedded in gels could be patterned by culturing MDA-MB-231 metastatic breast cancer cells and RAW 264.1 macrophage cells within distinct collagen type I and Matrigel ECM environments, respectively. Over a 7 day culture experiment, RAW cells invaded into neighboring gels containing MDA-MB-231 cells, but not into gels lacking cells. These studies demonstrate the versatility and potential of this new microfluidic platform to engineer 3D microscale architectures to investigate cell-cell and cell-matrix interactions.
引用
收藏
页码:1740 / 1748
页数:9
相关论文
共 50 条
[41]   Rheological Characterization of Three-Dimensional Neuronal Cultures Embedded in PEGylated Fibrin Hydrogels [J].
Lopez-Leon, Clara F. ;
Soriano, Jordi ;
Planet, Ramon .
GELS, 2023, 9 (08)
[42]   Three-dimensional Micro-culture System for Tooth Tissue Engineering [J].
Kuchler-Bopp, S. ;
Becavin, T. ;
Kokten, T. ;
Weickert, J. L. ;
Keller, L. ;
Lesot, H. ;
Deveaux, E. ;
Benkirane-Jessel, N. .
JOURNAL OF DENTAL RESEARCH, 2016, 95 (06) :657-664
[43]   Directing three-dimensional multicellular morphogenesis by self-organization of vascular mesenchymal cells in hyaluronic acid hydrogels [J].
Zhu, Xiaolu ;
Gojgini, Shiva ;
Chen, Ting-Hsuan ;
Fei, Peng ;
Dong, Siyan ;
Ho, Chih-Ming ;
Segura, Tatiana .
JOURNAL OF BIOLOGICAL ENGINEERING, 2017, 11
[44]   Liver three-dimensional cellular models for high-throughput chemical testing [J].
Yang, Shu ;
Ooka, Masato ;
Margolis, Ryan Jared ;
Xia, Menghang .
CELL REPORTS METHODS, 2023, 3 (03)
[45]   Construction of Multicellular Neural Tissue Using Three-Dimensional Printing Technology: Cell Interaction [J].
Li, Zhixiang ;
Su, Tong ;
Yang, Yujie ;
Zhao, Huan .
TISSUE ENGINEERING PART B-REVIEWS, 2025,
[46]   Three-dimensional bioprinting in tissue engineering and regenerative medicine [J].
Guifang Gao ;
Xiaofeng Cui .
Biotechnology Letters, 2016, 38 :203-211
[47]   Three-dimensional macroporous graphene scaffolds for tissue engineering [J].
Lalwani, Gaurav ;
D'agati, Michael ;
Gopalan, Anu ;
Rao, Manisha ;
Schneller, Jessica ;
Sitharaman, Balaji .
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2017, 105 (01) :73-83
[48]   Three-Dimensional Bioprinting Applications for Bone Tissue Engineering [J].
Maresca, Jamie A. A. ;
DeMel, Derek C. C. ;
Wagner, Grayson A. A. ;
Haase, Colin ;
Geibel, John P. P. .
CELLS, 2023, 12 (09)
[49]   Three-Dimensional Printing for Craniofacial Bone Tissue Engineering [J].
Shen, Chen ;
Witek, Lukasz ;
Flores, Roberto L. ;
Tovar, Nick ;
Torroni, Andrea ;
Coelho, Paulo G. ;
Kasper, F. Kurtis ;
Wong, Mark ;
Young, Simon .
TISSUE ENGINEERING PART A, 2020, 26 (23-24) :1303-1311
[50]   Three-Dimensional Bioprinting: The Ultimate Pinnacle of Tissue Engineering [J].
Arumugam, Parkavi ;
Kaarthikeyan, G. ;
Eswaramoorthy, Rajalakshmanan .
CUREUS JOURNAL OF MEDICAL SCIENCE, 2024, 16 (04)