Table 1.
Summary of 3D tumor spheroid—microvascular-on-a-chip models
| Tissue | Cell sources (EC/Spheroid) | Approaches (Vascularization/Spheroid formation) | Features | Refs |
|---|---|---|---|---|
| Lung | HUVECs/A549 | Endothelial cell monolayer/Ultra-low attachment dish | Investigated dispersion of cancer cells and increased EMT marker in the model, tested drug targeting EMT and analyzed cellular response | [201] |
| Colon | ECFCs/SW620 with ECFCs | Self-assembled network/Non-adherent round-bottom 96-well plate | Constructed vascularized breast and lung spheroids with robust sprouting and a lumenized vessel network and analyzed increased tumor cell intravasation as oxygen decreased | [202] |
| Brain | HDMECs/U87MG | Self-assembled network/Hanging drop-cell culture dish | Reconstituted the capillary beds-tumor tissue interaction using an “open-top” microfluidic chip and compared the vascular architecture with spheroid with the one without spheroid | [203] |
| Colon | HUVECs and HDLECs/SW620 with NHLFs | Self-assembled network/ Hanging drop | Reconstructed simultaneous angiogenesis/lymphangiogenesis to tumor-stroma spheroid and observed the physical interactions between the sprouts and tumor cells | [204] |
| Ovary | HUVECs/SKOV3 |
Endothelial cell monolayer/ 96-well plate precoated with agarose |
Investigated no significant cellular uptake differences of the targeted and untargeted nanoparticles in the microfluidic and in vivo model in contrast to the control condition | [205] |
| Colon and stomach | HUVECs/SW620 and MKN74 with NHLFs, each |
Self-assembled network/ Microwell plate |
Analyzed angiogenic sprouts in the mineralized colorectal/gastric TME by varying the concentration of hydroxyapatite | [206] |
| Brain | HUVECs/U87MG and HepG2 |
Self-assembled network/ Non-adherent round-bottom 96-well plate |
Quantified the vascular network area, number of sprouts, and sprouting length after anti-cancer drug screening in tumor spheroid-induced angiogenesis | [207] |
| Lung | HUVECs/A549 |
Self-assembled network/ Non-adherent round-bottom 96-well plate |
Investigated vascular responses to chemotherapy, including vascular architecture, endothelial apoptosis, and oxidative stress, as well as demonstrated the cytotoxic effect localized at the outer surface of the traditional spheroid model in contrast to the microfluidic model | [208] |
| Breast | HUVECs/MCF7 |
Tubular endothelial barrier/ Hanging drop-cell culture dish lid |
Presented fast penetration of natural killer cells to the tumor spheroid compared with antibodies and enhanced cytotoxicity for the spheroid periphery using the combination therapy | [209] |
| Breast | HUVECs/MCF7 with NHLFs and HUVECs | Self-assembled network/ Non-adherent round-bottom 96-well plate | Demonstrated the adaptability of the model to other cancer cells (HepG2, MDA-MB-231, and SW620) and perfusability of the network, and analyzed the dose-dependent effects of chemotherapy on the response of the tumor spheroids using the model | [210] |
| Ovary and lung | HUVECs/SKOV3 and A549 | Self-assembled network/ Non-adherent round-bottom 96-well plate | Constructed a 3D tumor spheroid-perfusable microvascular network interaction to examine the effects of chemotherapy, drug resistance, and molecular diffusivity in the microenvironment | [211] |
HUVECs, human umbilical vein cells; EMT, epithelial-mesenchymal transition; ECFCs, endothelial colony-forming cells; HDMEC, human dermal microvascular endothelial cells; HDLEC, human dermal lymphatic endothelial cells; NHLFs, normal human lung fibroblasts