Methods | Concept | Advantages | Disadvantages | Cell types | Results | References |
---|---|---|---|---|---|---|
Scaffold-based | Cells adsorb and migrate into solid materials to form micro-tissues. | The simplicity of fabrication and the diversity of materials Appropriate physical support Resist the outside environment | Harvesting cells from the scaffold is difficult and possibly harmful to the cells. Suitable for tissue engineering research, not for drug screening. | Lung adenocarcinoma cells (HCC), macrophages and lung fibroblasts | Cocultivation promoted the metastatic phenotype due to the excretion of both matrix metalloproteinase-1(MMP-1) and vascular endothelial growth factor (VEGF). | (Liu et al. 2016) |
Non-small cell lung cancer (NSCLC) | Compared with 2D culture model, IC50 value of anticancer drugs in MTSs was significantly increased. | (Godugu et al. 2013) | ||||
Breast cancer cells (MCF-7) | Compared with monolayer cells, 3D MTSs-CCA system was superior to 2D culture system in anticancer drug screening. | (Wang et al. 2016) | ||||
Hanging drop | Cells form a single cluster by dropping a cell suspension onto an inverted glass covering surface by gravity. | Mild conditions Simple materials Without shear force Easy to control the number, size and shape of spheroids | Medium changed frequently Time-consuming and labor-intensive Hard to scale-up Limited applicability in drug screening Limited culture time | Colon cancer cells (HT‑29) | Encapsulation of anticancer drugs in liposomes could improve the therapeutic effect. | (Galateanu et al. 2016) |
Malignant melanoma cells (A375) | MTS was an effective tool for investigating the biological effects of oligonucleotides. | (Carver et al. 2014) | ||||
Pulmonary epithelial cells (EPI), pulmonary vascular endothelial cells (ENDO) and human bone marrow mesenchymal stem cells (MSC) | Compared with 2D culture, the expression of ROS and ABCB1 was enhanced and drug resistance was increased. | (Lamichhane et al. 2016) | ||||
Liquid covering | Cells aggregate on non-adherent plates. | Easy to operate Low cost Large-scale production High-throughput screening of drugs | Poor consistency Static culture Difficult to guarantee cell activity | Lung cancer cell lines, breast cancer cell lines, pancreatic cancer cell lines and fibroblasts (MRC5) | After co-culture of tumor cells with fibroblasts, the survival of co-culture cells increased by four times than monoculture cells due to the secretion of soluble factors. | (Majety et al. 2015) |
Pancreatic cancer cells (PANC-1), fibroblasts (MRC-5) and endothelial cells (HUVEC) | The complex microenvironment reduced chemotherapy sensitivity. MTSs could be used in drug screening for pancreatic cancer. | (Lazzari et al. 2018) | ||||
Breast cancer cells (MCF-7), cervical cancer cells (Hela) and primary normal human skin fibroblasts (hFIB) | When the cancer cells were co-cultured with hFIB, dense necrotic cores in the tumor spheroids could be observed. | (Costa et al. 2014) | ||||
Breast cancer cells (MCF-7) and mouse fibroblasts (NIH-3T3) | When co-cultured with NIH-3T3, the resistance or IC50 of MCF-7 significantly increased. | (Xin and Yang 2019) | ||||
U-87 MG glioblastoma and other 40 tumor cell lines | 2D and 3D culture models exhibited different sensitivities to targeted drugs. | (Vinci et al. 2012) | ||||
Colorectal cancer (CRC) cells | MTSs with hypoxia and multicellular tumor necrosis areas displayed closer gene expression landscape to tumors in vivo. | (Däster et al. 2017) | ||||
Ovarian cancer cells (NCI-ADR-RES) | Targeted modified drugs were more likely to cross the permeable barrier and accumulate in spheroid. | (Perche et al. 2012) | ||||
Epithelial ovarian cancer (EOC) cells | The response of MTSs to anticancer drugs reduced compared with monolayer culture. | (Liao et al. 2014) | ||||
Colon cancer cells (Caco-2 and DLD-1) and Peripheral blood mononuclear cell (PBMC) | Co-cultured tumor cells were more resistant to 5-FU/Oxaliplatin (FO) than single cultured tumor cells. | (Hoffmann et al. 2015) | ||||
Micromachining wells | Cells cluster in a matrix of micromachining wells. | High reproducibility Uniform size and shape High-throughput mechanized production | High cost Specific device | Breast cancer cells (LCC6/Her-2) | Compared with traditional monolayer culture, tumor spheroids showed resistance to dose-dependent responses to DOX and anticancer drugs. | (Yu et al. 2010) |
Breast cancer cells (MCF-7) | MTSs retained the physiologic features of solid tumors, thus leading to the understanding of the response of tumor to chemotherapy and radiation therapy. | (Markovitz-Bishitz et al. 2010) | ||||
Dynamic techniques based on agitation | Cells aggregate by continuous stirring in specific reactors. | Suitable for long-term culture Easy to operate Large-scale industrialization Controllable condition | Shear force affects cells. Difficult to control shape, size and quantity Specific device | Hepatocellular carcinoma cells (Huh7) and endothelial cells (HUVEC) | The co-cultured spheroids were more resistant to anticancer drugs (Adriamycin and Sorafenib) than the monolayer cells. | (Jung et al. 2017) |
Colon cancer cells (HT‑29) | Glycolysis, TCA cycle and lipid metabolism-related protein expression from inside MTSs was higher than outside MTSs. | (McMahon et al. 2012) |