journal article·2022-09

Scalable Formation of Highly Viable and Functional Hepatocellular Carcinoma Spheroids in an Oxygen‐Permeable Microwell Device for Anti‐Tumor Drug Evaluation

Jianyu He, Chang Zhou, Xiaolei Xu, Zhenzhen Zhou, Mathieu Danoy, Marie Shinohara, Wenjin Xiao, Dong Zhu, Xiuying Zhao, Xiaobin Feng, Yilei Mao, Wei Sun, Yasuyuki Sakai, Huayu Yang, Yuan Pang

Advanced Healthcare Materials· Volume 11· Issue 18
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Abstract

Abstract For high‐throughput anti‐cancer drug screening, microwell arrays may serve as an effective tool to generate uniform and scalable tumor spheroids. However, microwell arrays are commonly anchored in non‐oxygen‐permeable culture plates, leading to limited oxygen supply for avascular spheroids. Herein, a polydimethylsiloxane (PDMS)‐based oxygen‐permeable microwell device is introduced for generating highly viable and functional hepatocellular carcinoma (HCC) spheroids. The PDMS sheets at the bottom of the microwell device provide a high flux of oxygen like in vivo neighboring hepatic sinusoids. Owing to the better oxygen supply, the generated HepG2 spheroids are larger in size and exhibit higher viability and proliferation with less cell apoptosis and necrosis. These spheroids also exhibit lower levels of anaerobic cellular respiration and express higher levels of liver‐related functions. In anti‐cancer drug testing, spheroids cultured in PDMS plates show a significantly stronger resistance against doxorubicin because of the stronger stem‐cell and multidrug resistance phenotype. Moreover, higher expression of vascular endothelial growth factor‐A produces a stronger angiogenesis capability of the spheroids. Overall, compared to the spheroids cultured in conventional non‐oxygen‐permeable plates, these spheroids can be used as a more favorable model for early‐stage HCCs and be applied in high‐throughput anti‐cancer drug screening.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: 3D Printing in Biomedical Research · Cancer Cells and Metastasis · Innovative Microfluidic and Catalytic Techniques Innovation

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Biomanufacturing Center Department of Mechanical Engineering Tsinghua University Haidian District Beijing 100084 P. R. China

Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Tsinghua University Beijing 100084 P. R. China

Key Laboratory for Advanced Materials Processing Technology Ministry of Education Beijing 100084 P. R. China

Department of Hepatobiliary Surgery Beijing Tsinghua Changgung Hospital School of Clinical Medicine Tsinghua University Changping District Beijing 102218 P. R. China

Department of Chemical System Engineering Graduate School of Engineering University of Tokyo Tokyo 113‐033 Japan

Institute of Industrial Science University of Tokyo Tokyo 153–8505 Japan

Centre de Recherche des Cordeliers INSERM UMR‐S1138 CNRS SNC5014 University of Paris Paris 75006 France

Clinical Laboratory Beijing Tsinghua Changgung Hospital School of Clinical Medicine Tsinghua University Changping District Beijing 102218 P. R. China

Department of Liver Surgery Peking Union Medical College (PUMC) Hospital PUMC & Chinese Academy of Medical Sciences (CAMS) Dongcheng District Beijing 100005 P. R. China

Department of Mechanical Engineering and Mechanics College of Engineering Drexel University Philadelphia PA 19104 USA

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Higher Education Discipline Innovation Project

References (65)

Show source-provided references
1. 10.3322/caac.2166010.3322/caac.21660 ↗
2. 10.1016/j.cell.2011.02.01310.1016/j.cell.2011.02.013 ↗
3. 10.1016/j.drudis.2016.06.02410.1016/j.drudis.2016.06.024 ↗
4. 10.1002/bit.2684510.1002/bit.26845 ↗
5. 10.1016/j.pharmthera.2016.03.01310.1016/j.pharmthera.2016.03.013 ↗
6. 10.18063/ijb.v7i4.44410.18063/ijb.v7i4.444 ↗
7. 10.1016/j.jconrel.2012.04.04510.1016/j.jconrel.2012.04.045 ↗
8. 10.1111/cas.1315510.1111/cas.13155 ↗
9. 10.4155/tde.15.110.4155/tde.15.1 ↗
10. 10.3390/bios1112051410.3390/bios11120514 ↗
11. 10.1038/nprot.2008.22610.1038/nprot.2008.226 ↗
12. 10.1038/s41578-020-0199-810.1038/s41578-020-0199-8 ↗
13. 10.1089/ten.teb.2016.046510.1089/ten.teb.2016.0465 ↗
14. 10.1002/biot.20170041710.1002/biot.201700417 ↗
15. 10.1039/C0AN00609B10.1039/C0AN00609B ↗
16. 10.1007/s13233-018-6002-710.1007/s13233-018-6002-7 ↗
17. 10.1002/adhm.20150010710.1002/adhm.201500107 ↗
18. 10.1038/s41598-017-18050-110.1038/s41598-017-18050-1 ↗
19. 10.1371/journal.pone.013034810.1371/journal.pone.0130348 ↗
20. 10.1039/C9LC00872A10.1039/C9LC00872A ↗
21. 10.1088/1758-5090/ac044c10.1088/1758-5090/ac044c ↗
22. 10.1089/adt.2015.66210.1089/adt.2015.662 ↗
23. 10.1039/C7LC00832E10.1039/C7LC00832E ↗
24. 10.3390/mi710017310.3390/mi7100173 ↗
25. 10.1016/j.biomaterials.2015.05.01310.1016/j.biomaterials.2015.05.013 ↗
26. 10.1371/journal.pone.007334510.1371/journal.pone.0073345 ↗
27. 10.1016/j.ddtec.2017.03.00210.1016/j.ddtec.2017.03.002 ↗
28. 10.1063/1.357690510.1063/1.3576905 ↗
29. 10.1002/adhm.20130015110.1002/adhm.201300151 ↗
30. 10.1016/j.jhep.2021.12.02810.1016/j.jhep.2021.12.028 ↗
31. 10.1007/s11605-008-0652-210.1007/s11605-008-0652-2 ↗
32. 10.1158/1078-0432.CCR-18-125410.1158/1078-0432.CCR-18-1254 ↗
33. 10.1039/c3bm00123g10.1039/c3bm00123g ↗
34. 10.3389/fbioe.2020.0052410.3389/fbioe.2020.00524 ↗
35. 10.1530/EC-17-034910.1530/EC-17-0349 ↗
36. 10.1016/j.biomaterials.2015.09.03210.1016/j.biomaterials.2015.09.032 ↗
37. 10.1088/1758-5090/8/3/03501610.1088/1758-5090/8/3/035016 ↗
38. 10.1088/1758-5082/4/4/04500410.1088/1758-5082/4/4/045004 ↗
39. 10.1002/btpr.183710.1002/btpr.1837 ↗
40. 10.1088/2057-1976/aa7c3d10.1088/2057-1976/aa7c3d ↗
41. 10.21037/atm-20-159810.21037/atm-20-1598 ↗
42. 10.1039/C5LC01499A10.1039/C5LC01499A ↗
43. 10.1517/14712598.2012.70718110.1517/14712598.2012.707181 ↗
44. 10.1186/s40643-020-00325-710.1186/s40643-020-00325-7 ↗
45. 10.1039/C4BM00319E10.1039/C4BM00319E ↗
46. 10.1002/biot.20070022810.1002/biot.200700228 ↗
47. 10.1007/s10544-010-9403-810.1007/s10544-010-9403-8 ↗
48. 10.1016/j.trac.2020.11596110.1016/j.trac.2020.115961 ↗
49. 10.1248/bpb.b16-0083310.1248/bpb.b16-00833 ↗
50. 10.1016/j.bbrc.2016.11.06210.1016/j.bbrc.2016.11.062 ↗
51. 10.1053/j.gastro.2008.12.00410.1053/j.gastro.2008.12.004 ↗
52. 10.1159/00034386310.1159/000343863 ↗
53. 10.2353/ajpath.2007.07015210.2353/ajpath.2007.070152 ↗
54. 10.1016/j.trecan.2016.10.01610.1016/j.trecan.2016.10.016 ↗
55. 10.1371/journal.pone.016123910.1371/journal.pone.0161239 ↗
56. 10.1371/journal.pone.014949210.1371/journal.pone.0149492 ↗
57. 10.1007/s12032-019-1329-210.1007/s12032-019-1329-2 ↗
58. 10.1053/j.gastro.2013.01.00210.1053/j.gastro.2013.01.002 ↗
59. 10.1038/nrclinonc.2011.3010.1038/nrclinonc.2011.30 ↗
60. 10.1186/1471-2407-12-410.1186/1471-2407-12-4 ↗
61. 10.1016/j.jbiosc.2011.01.00610.1016/j.jbiosc.2011.01.006 ↗
62. 10.1038/nrd280310.1038/nrd2803 ↗
63. 10.1074/jbc.M10014120010.1074/jbc.M100141200 ↗
64. 10.1053/j.gastro.2012.06.03810.1053/j.gastro.2012.06.038 ↗
65. 10.1016/j.febslet.2005.06.07810.1016/j.febslet.2005.06.078 ↗