Biomedical Sciences ETDs
Publication Date
Summer 7-10-2018
Abstract
Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation techniques have the ability to encapsulate cancer cells in droplets for standardized and more realistic 3D cell culture and cancer biology applications. Three individual droplet generating platforms have been designed and optimized for droplet-based cell encapsulation. Each has its own advancements and challenges. Together, however, these technologies accomplish medium to high-throughput generation (10 droplets/second to 25,000 droplets/second) of biomaterial droplets for encapsulation of a range of cell occupancies (5 cells/droplet to 400 cells/droplet). The data presented also demonstrates the controlled generation of cell-sized small droplets for biomolecule compartmentalization, droplets with diameters ranging between 100-400 μm depending on device parameters, and the generation of instant spheroids. Standardized assays for analyzing cells grown within these new 3D environments include proliferation assays of cells grown in mono- and co-cultures, the generation of large and uniform populations of scaffold supported multicellular spheroids, and a new system for culturing encapsulated cells in altered environmental conditions.
Keywords
droplets, microfluidics, cell encapsulation, hypoxia, acidosis, spheroids
Document Type
Dissertation
Language
English
Degree Name
Biomedical Sciences
Level of Degree
Doctoral
Department Name
Biomedical Sciences Graduate Program
First Committee Member (Chair)
Helen J. Hathaway
Second Committee Member
James P. Freyer
Third Committee Member
Diane S. Like
Fourth Committee Member
Andrew P. Shreve
Recommended Citation
De Lora, Jacqueline A.. "Developing Droplet Based 3D Cell Culture Methods to Enable Investigations of the Chemical Tumor Microenvironment." (2018). https://digitalrepository.unm.edu/biom_etds/186
Included in
Bioimaging and Biomedical Optics Commons, Biological Engineering Commons, Biomaterials Commons, Biomedical Devices and Instrumentation Commons, Biophysics Commons, Biotechnology Commons, Cancer Biology Commons, Cell Biology Commons, Disease Modeling Commons, Molecular, Cellular, and Tissue Engineering Commons
