Multi-Domain Photopatterned 3D Tumor Constructs in a Micro-Physiological System for Analysis, Quantification, and Isolation of Infiltrating Cells.
Adv Biosyst
; 4(4): e1900273, 2020 04.
Article
in En
| MEDLINE
| ID: mdl-32293164
ABSTRACT
Cancer cell motility plays a central role in metastasis and tumor invasion but can be difficult to study accurately in vitro. A simple approach to address this challenge through the production of monolithic, photopatterned 3D tumor constructs in situ in a microfluidic device is described here. Through step-wise fabrication of adjoining hydrogel regions with and without incorporated cells, multidomain structures with defined boundaries are produced. By imaging cells over time, cellular activity with arbitrary control over medium conditions, including drug concentration and flow rate, is studied. First, malignant human colon carcinoma cells (HCT116) are studied for 10 days, comparing invasion dynamics and viability of cells in normal media to those exposed to two independent chemotherapeutic drugs anti-proliferative 5-fluorouracil and anti-migratory Marimastat. Cytotoxicity is measured and significant differences are observed in cellular dynamics (migrating cell count, distance traveled, and rate) that correlate with the mechanism of each drug. Then, the platform is applied to the selective isolation of infiltrated cells through the photopatterning and subsequent dissolution of cleavable hydrogel domains. As a demonstration, the preferential collection of highly migratory cells (HCT116) over a comparable cell line with low malignancy and migratory potential (Caco-2) is shown.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colonic Neoplasms
/
Hydrogels
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Lab-On-A-Chip Devices
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Fluorouracil
/
Hydroxamic Acids
Limits:
Humans
Language:
En
Journal:
Adv Biosyst
Year:
2020
Document type:
Article
Affiliation country:
United States