Incorporation of multicellular spheroids into 3‐D polymeric scaffolds provides an improved tumor model for screening anticancer drugs
Development of cancer therapeutics requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Three‐dimensional (3‐D) in vitro models have therefore been investigated for drug screening. In this study, we have developed a novel in vitro model in wh...
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| Published in | Cancer science Vol. 101; no. 12; pp. 2637 - 2643 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford, UK
Blackwell Publishing Ltd
01.12.2010
Blackwell |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Development of cancer therapeutics requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Three‐dimensional (3‐D) in vitro models have therefore been investigated for drug screening. In this study, we have developed a novel in vitro model in which multicellular aggregates, or spheroids, were incorporated into 3‐D porous scaffolds. Drug resistance assays showed that spheroid‐seeded scaffolds have much higher drug resistance than monolayer cultures, spheroids on flat substrates, or scaffolds seeded with dispersed cells. Furthermore, spheroid‐seeded scaffolds demonstrated higher lactate production leading to acidosis, and higher expression of angiogenic factors. These data suggest that the spheroid‐seeded 3‐D scaffolds might serve as a useful in vitro system for screening cancer therapeutics. (Cancer Sci 2010; 101: 2637–2643) |
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| AbstractList | Development of cancer therapeutics requires a thorough evaluation of drug efficacy
in vitro
before animal testing and subsequent clinical trials. Three‐dimensional (3‐D)
in vitro
models have therefore been investigated for drug screening. In this study, we have developed a novel
in vitro
model in which multicellular aggregates, or spheroids, were incorporated into 3‐D porous scaffolds. Drug resistance assays showed that spheroid‐seeded scaffolds have much higher drug resistance than monolayer cultures, spheroids on flat substrates, or scaffolds seeded with dispersed cells. Furthermore, spheroid‐seeded scaffolds demonstrated higher lactate production leading to acidosis, and higher expression of angiogenic factors. These data suggest that the spheroid‐seeded 3‐D scaffolds might serve as a useful
in vitro
system for screening cancer therapeutics. (
Cancer Sci
2010; 101: 2637–2643) Development of cancer therapeutics requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Three-dimensional (3-D) in vitro models have therefore been investigated for drug screening. In this study, we have developed a novel in vitro model in which multicellular aggregates, or spheroids, were incorporated into 3-D porous scaffolds. Drug resistance assays showed that spheroid-seeded scaffolds have much higher drug resistance than monolayer cultures, spheroids on flat substrates, or scaffolds seeded with dispersed cells. Furthermore, spheroid-seeded scaffolds demonstrated higher lactate production leading to acidosis, and higher expression of angiogenic factors. These data suggest that the spheroid-seeded 3-D scaffolds might serve as a useful in vitro system for screening cancer therapeutics. Development of cancer therapeutics requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Three-dimensional (3-D) in vitro models have therefore been investigated for drug screening. In this study, we have developed a novel in vitro model in which multicellular aggregates, or spheroids, were incorporated into 3-D porous scaffolds. Drug resistance assays showed that spheroid-seeded scaffolds have much higher drug resistance than monolayer cultures, spheroids on flat substrates, or scaffolds seeded with dispersed cells. Furthermore, spheroid-seeded scaffolds demonstrated higher lactate production leading to acidosis, and higher expression of angiogenic factors. These data suggest that the spheroid-seeded 3-D scaffolds might serve as a useful in vitro system for screening cancer therapeutics. (Cancer Sci 2010; 101: 2637-2643) Development of cancer therapeutics requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Three-dimensional (3-D) in vitro models have therefore been investigated for drug screening. In this study, we have developed a novel in vitro model in which multicellular aggregates, or spheroids, were incorporated into 3-D porous scaffolds. Drug resistance assays showed that spheroid-seeded scaffolds have much higher drug resistance than monolayer cultures, spheroids on flat substrates, or scaffolds seeded with dispersed cells. Furthermore, spheroid-seeded scaffolds demonstrated higher lactate production leading to acidosis, and higher expression of angiogenic factors. These data suggest that the spheroid-seeded 3-D scaffolds might serve as a useful in vitro system for screening cancer therapeutics.Development of cancer therapeutics requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Three-dimensional (3-D) in vitro models have therefore been investigated for drug screening. In this study, we have developed a novel in vitro model in which multicellular aggregates, or spheroids, were incorporated into 3-D porous scaffolds. Drug resistance assays showed that spheroid-seeded scaffolds have much higher drug resistance than monolayer cultures, spheroids on flat substrates, or scaffolds seeded with dispersed cells. Furthermore, spheroid-seeded scaffolds demonstrated higher lactate production leading to acidosis, and higher expression of angiogenic factors. These data suggest that the spheroid-seeded 3-D scaffolds might serve as a useful in vitro system for screening cancer therapeutics. |
| Author | Kim, Jae H. Ho, Won Jin Pham, Edward A. Kamei, Daniel T. Wu, Benjamin M. Kim, Jun W. Ng, Christopher W. |
| AuthorAffiliation | 1 Department of Bioengineering, University of California, Los Angeles, California, USA |
| AuthorAffiliation_xml | – name: 1 Department of Bioengineering, University of California, Los Angeles, California, USA |
| Author_xml | – sequence: 1 givenname: Won Jin surname: Ho fullname: Ho, Won Jin – sequence: 2 givenname: Edward A. surname: Pham fullname: Pham, Edward A. – sequence: 3 givenname: Jun W. surname: Kim fullname: Kim, Jun W. – sequence: 4 givenname: Christopher W. surname: Ng fullname: Ng, Christopher W. – sequence: 5 givenname: Jae H. surname: Kim fullname: Kim, Jae H. – sequence: 6 givenname: Daniel T. surname: Kamei fullname: Kamei, Daniel T. – sequence: 7 givenname: Benjamin M. surname: Wu fullname: Wu, Benjamin M. |
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| Keywords | Antineoplastic agent Drug Incorporation Cancerology Tumor Models Spheroid Medical screening |
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| SubjectTerms | Biological and medical sciences Drug Screening Assays, Antitumor - methods Humans Medical sciences Original Spheroids, Cellular - cytology Spheroids, Cellular - drug effects Tissue Scaffolds Tumor Cells, Cultured - cytology Tumor Cells, Cultured - drug effects Tumors |
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| Title | Incorporation of multicellular spheroids into 3‐D polymeric scaffolds provides an improved tumor model for screening anticancer drugs |
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