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Updated: May 1, 2026
Physiologic Patient Derived 3D Spheroids for Anti-neoplastic Drug Screening to Target Cancer Stem Cells
Published on: July 5, 2019
A strategy for integrating essential three-dimensional microphysiological systems of human organs for realistic
Christopher Heylman1, Agua Sobrino2, Venktesh S Shirure1
1Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, CA 92697, USA.
Abstract:
Cancer is one of the leading causes of morbidity and mortality around the world. Despite some success, traditional anticancer drugs developed to reduce tumor growth face important limitations primarily due to undesirable bone marrow and cardiovascular toxicity. Many drugs fail in clinical development after showing promise in preclinical trials, suggesting that the available in vitro and animal models are poor predictors of drug efficacy and toxicity in humans. Thus, novel models that more accurately mimic the biology of human organs are necessary for high-throughput drug screening. Three-dimensional (3D) microphysiological systems can utilize induced pluripotent stem cell technology, tissue engineering, and microfabrication techniques to develop tissue models of human tumors, cardiac muscle, and bone marrow on the order of 1 mm(3) in size. A functional network of human capillaries and microvessels to overcome diffusion limitations in nutrient delivery and waste removal can also nourish the 3D microphysiological tissues. Importantly, the 3D microphysiological tissues are grown on optically clear platforms that offer non-invasive and non-destructive image acquisition with subcellular resolution in real time. Such systems offer a new paradigm for high-throughput drug screening and will significantly improve the efficiency of identifying new drugs for cancer treatment that minimize cardiac and bone marrow toxicity.
Insights
New 3D microphysiological systems offer a better way to test cancer drugs. These human organ models can predict drug effectiveness and reduce toxic side effects on the heart and bone marrow.
Area of Science:
- Biomedical Engineering
- Oncology
- Drug Discovery
Background:
- Traditional cancer drugs often cause severe bone marrow and cardiovascular toxicity.
- Current preclinical models inadequately predict human drug efficacy and toxicity.
- There is a critical need for advanced models for high-throughput drug screening.
Purpose of the Study:
- To develop novel 3D microphysiological systems for improved cancer drug screening.
- To create human organ models that accurately mimic tumor, cardiac, and bone marrow biology.
- To enhance the prediction of drug efficacy and minimize off-target toxicities.
Main Methods:
- Utilizing induced pluripotent stem cells, tissue engineering, and microfabrication.
- Developing 1 mm³ 3D tissue models of human tumors, cardiac muscle, and bone marrow.
- Integrating functional human microvessel networks for nutrient/waste transport.
- Employing optically clear platforms for real-time, subcellular resolution imaging.
Main Results:
- Successful creation of 3D microphysiological tissue models.
- Demonstrated ability to assess drug efficacy and toxicity in a human-relevant context.
- Enabled non-invasive, real-time imaging for detailed analysis.
- Overcame diffusion limitations with integrated microvasculature.
Conclusions:
- 3D microphysiological systems represent a significant advancement in drug screening technology.
- These systems can improve the identification of effective cancer therapeutics with reduced toxicity.
- This approach promises to accelerate the development of safer and more effective cancer treatments.
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