Chemotaxis-driven assembly of endothelial barrier in a tumor-on-a-chip platform.
The integration of three-dimensional micropatterning with microfluidics provides a unique opportunity to create perfusable tissue constructs in vitro. Herein, we have used this approach to create a tumor-on-a-chip with an endothelial barrier. Specifically, we photopatterned a mixture of endothelial cells and cancer spheroids within a gelatin methacrylate (GelMA) hydrogel inside a microfluidic device. The differential motility of endothelial and cancer cells in response to a controlled morphogen gradient across the cell-laden network drove the migration of endothelial cells to the periphery while maintaining the cancer cells within the interior of the hydrogel. The resultant endothelial cell layer forming cell-cell contact via VE-cadherin junctions was found to encompass the entire GelMA hydrogel structure. Furthermore, we have also examined the potential of such a tumor-on-a-chip system as a drug screening platform using doxorubicin, a model cancer drug.
Department of Bioengineering, University of California-San Diego, La Jolla, CA, USA. svarghese@ucsd.edu.
Aereas
A
Aung
Jomkuan
J
Theprungsirikul
Han Liang
HL
Lim
Shyni
S
Varghese
D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D002465:Cell Movement; D002633:Chemotaxis; D018920:Coculture Techniques / Q000295:instrumentation / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation* / Q000379:methods; D042783:Endothelial Cells; D005780:Gelatin / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D056656:Lab-On-A-Chip Devices; D061986:MCF-7 Cells; D008689:Methacrylates / Q000737:chemistry; D044085:Microfluidics / Q000295:instrumentation*; D018874:Spheroids, Cellular / Q000473:pathology*; D059016:Tumor Microenvironment; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D004317:Doxorubicin; D005780:Gelatin; D008689:Methacrylates; D000099152:Cadherin 5