title: A polymer microstructure array for the formation, culturing, and high throughput drug screening of breast cancer spheroids.
abstract: Multicellular spheroid models have been recognized as superior to monolayer cell cultures in antitumor drug screening, but their commercial adaptation in the pharmaceutical industry has been delayed, primarily due to technological limitations. The current study presents a new spheroid culture platform that addresses these technical restrictions. The new culturing device is based on a multiwell plate equipped with a glass bottom patterned with an array of UV adhesive microchambers. Each microchamber is designed to accommodate a single spheroid. The system facilitates the simultaneous creation and culturing of a large number of spheroids, as well as screening their response to antitumor drugs. The volume of the spheroids is easily controlled by seeding density. The location of each spheroid is preserved in the same microchamber throughout its growth, treatment with soluble agents, and imaging. The growth ratio parameter, a non-intrusive size analysis of the same spheroid before and after exposure to drugs, was found to be a sensitive indicator for the reaction of MCF7 breast cancer spheroids to cytotoxic drugs. This feature helps reveal the heterogeneity within the spheroid population during the formation process and their drug response, and provides an opportunity to detect specific, highly active or drug-resistant spheroid sub-groups. The advantages of this spheroid-based system make it an efficient drug-screening tool that may be valuable to related fields of research and clinical applications.
authors.affiliation: The Biophysical Interdisciplinary Schottenstein Center for the Research and Technology of the Cellome, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Markovitz-Bishitz
authors.forename: Yishay
authors.initials: Y
authors.lastname: Tauber
authors.forename: Elena
authors.initials: E
authors.lastname: Afrimzon
authors.forename: Naomi
authors.initials: N
authors.lastname: Zurgil
authors.forename: Maria
authors.initials: M
authors.lastname: Sobolev
authors.forename: Yana
authors.initials: Y
authors.lastname: Shafran
authors.forename: Assaf
authors.initials: A
authors.lastname: Deutsch
authors.forename: Steffen
authors.initials: S
authors.lastname: Howitz
authors.forename: Mordechai
authors.initials: M
authors.lastname: Deutsch
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D005260:Female; D057166:High-Throughput Screening Assays / Q000295:instrumentation* / Q000379:methods; D006801:Humans; D011108:Polymers / Q000737:chemistry*; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers