Abstract
Colorectal cancer is the second leading cause of cancer death worldwide. Significant advances in the molecular mechanisms underlying colorectal cancer have been made; however, the clinical approval of new drugs faces many challenges. Drug discovery is a lengthy process causing a rapid increase in global health care costs. Patient-derived tumour organoids are considered preclinical models with the potential for preclinical drug screening, prediction of patient outcomes, and guiding optimized therapy strategies at an individual level. Combining microfluidic technology with 3D tumour organoid models to recapitulate tumour organization and in vivo functions led to the development of an appropriate preclinical tumour model, organoid-on-a-chip, paving the way for personalized cancer medicine. Herein, a low-cost microfluidic device suitable for culturing and expanding organoids, OrganoidChip, was developed. Patient-derived colorectal cancer organoids were cultured within OrganoidChip, and their viability and proliferative activity increased significantly. No significant differences were verified in the organoids’ response to 5-fluorouracil (5-FU) treatment on-chip and on-plate. However, the culture within the OrganoidChip led to a significant increase in colorectal cancer organoid-forming efficiency and overall size compared with conventional culture on a 24-well plate. Interestingly, early-stage and late-stage organoids were predominantly observed on-plate and within the OrganoidChip, respectively. The OrganoidChip thus has the potential to generate in vivo-like organotypic structures for disease modelling and drug screening applications.
Highlights
Colorectal cancer is the second leading cause of cancer death worldwide, and because of population ageing, the global burden is expected to grow to 2.5 million new cases in 2035 [1,2,3]
Our experiments showed a significant increase in organoid viability and proliferation within OrganoidChip, as well as similar sensitivity responses of colorectal cancer organoids to 5-FU on-chip and on-plate
Having designed and fabricated the microfluidic device, the OrganoidChip (Figure 2), we explored its feasibility for culturing organoids
Summary
Colorectal cancer is the second leading cause of cancer death worldwide, and because of population ageing, the global burden is expected to grow to 2.5 million new cases in 2035 [1,2,3]. Modelling cancer cell behaviour within the microfluidic device of tumour-on-chip, is highly physiological; enables co-cultures of different cell types; and offer precise control over physical, mechanical, and biochemical properties on the model. A microfluidic device was designed and fabricated through a milling process so as to culture and expand patient-derived colorectal cancer organoids on-chip (OrganoidChip). Our experiments showed a significant increase in organoid viability and proliferation within OrganoidChip, as well as similar sensitivity responses of colorectal cancer organoids to 5-FU on-chip and on-plate These observations demonstrate the potential of OrganoidChip to provide precise control of drug distribution, similar sensitivity, and improved growth culture conditions of colorectal cancer organoids. Late-stage colorectal cancer organoids were established within OrganoidChip, highlighting the potential for this micro-engineered organoid device to generate in vivo-like organotypic structures for disease modelling and drug screening applications
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