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Table 1 Summary of 3D tumor spheroid—microvascular-on-a-chip models

From: Microvascularized tumor organoids-on-chips: advancing preclinical drug screening with pathophysiological relevance

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
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]
  1. 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