Mammary Tumor Organoid Culture in Non-Adhesive Alginate for Luminal Mechanics and High-Throughput Drug Screening

Fang，Guocheng1; Lu，Hongxu1; Rodriguez de la Fuente，Laura2,3; Law，Andrew M.K.2,3; Lin，Gungun1; Jin，Dayong1,4; Gallego-Ortega，David1,2,3,5

2021

10.1002/advs.202102418

Advanced Science   影响因子和分区

2198-3844

Mammary tumor organoids have become a promising in vitro model for drug screening and personalized medicine. However, the dependency on the basement membrane extract (BME) as the growth matrices limits their comprehensive application. In this work, mouse mammary tumor organoids are established by encapsulating tumor pieces in non-adhesive alginate. High-throughput generation of organoids in alginate microbeads is achieved utilizing microfluidic droplet technology. Tumor pieces within the alginate microbeads developed both luminal- and solid-like structures and displayed a high similarity to the original fresh tumor in cellular phenotypes and lineages. The mechanical forces of the luminal organoids in the alginate capsules are analyzed with the theory of the thick-wall pressure vessel (TWPV) model. The luminal pressure of the organoids increase with the lumen growth and can reach 2 kPa after two weeks’ culture. Finally, the mammary tumor organoids are treated with doxorubicin and latrunculin A to evaluate their application as a drug screening platform. It is found that the drug response is related to the luminal size and pressures of organoids. This high-throughput culture for mammary tumor organoids may present a promising tool for preclinical drug target validation and personalized medicine.

alginate drug screening high-throughput luminal mechanics mammary tumor organoids microfluidic droplet

SCI ; EI

英语

其他

China Scholarship Council[201708140082] ; National Health and Medical Research Council (NHMRC)[GNT1160635] ; ARC Industry Transformational Research Hub Scheme[IH150100028] ; ARC Linkage Infrastructure, Equipment and Facilities (LIEF) Project[LE180100043] ; Cancer Council NSW[RG18-03] ; National Breast Cancer Foundation (Elaine Henry Fellowship)[IIRS-21-096] ; Chinese Australian Government["ACSRF65827","2017YFE0132300"] ; Australian Government["ACSRF65827","2017YFE0132300"]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000693659800001

WILEY

20213610875959

Adhesives ; Alginate ; Microbeads ; Personalized medicine ; Tumors

Biological Materials and Tissue Engineering:461.2 ; Medicine and Pharmacology:461.6 ; Organic Compounds:804.1

2-s2.0-85114375461

Scopus

1.Institute for Biomedical Materials and Devices,School of Mathematical and Physical Sciences,University of Technology Sydney,Sydney,Broadway Ultimo,2007,Australia
2.St. Vincent's Clinical School,Faculty of Medicine,University of New South Wales Sydney,Darlinghurst,2010,Australia
3.Garvan Institute of Medical Research,Darlinghurst,384 Victoria Street,2010,Australia
4.UTS-SUSTech Joint Research Centre for Biomedical Materials and Devices,Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,518055,China
5.School of Biomedical Engineering,Faculty of Engineering,University of Technology Sydney,Sydney,Broadway Ultimo,2007,Australia

Fang，Guocheng,Lu，Hongxu,Rodriguez de la Fuente，Laura,et al. Mammary Tumor Organoid Culture in Non-Adhesive Alginate for Luminal Mechanics and High-Throughput Drug Screening[J]. Advanced Science,2021,8.

Fang，Guocheng.,Lu，Hongxu.,Rodriguez de la Fuente，Laura.,Law，Andrew M.K..,Lin，Gungun.,...&Gallego-Ortega，David.(2021).Mammary Tumor Organoid Culture in Non-Adhesive Alginate for Luminal Mechanics and High-Throughput Drug Screening.Advanced Science,8.

Fang，Guocheng,et al."Mammary Tumor Organoid Culture in Non-Adhesive Alginate for Luminal Mechanics and High-Throughput Drug Screening".Advanced Science 8(2021).