Hypergravity-induced multicellular spheroid generation with different morphological patterns precisely controlled on a centrifugal microfluidic platform

In living tissue, cells exist in three-dimensional (3D) microenvironments with intricate cell-cell interactions. To model these cellular environments, numerous techniques for generating cell spheroids have been proposed and improved. However, previously reported methods still have limitations in uni...

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Bibliographic Details
Published in:Biofabrication 2017-11, Vol.9 (4), p.045006-045006
Main Authors: Park, Jiheum, Lee, Gi-Hun, Yull Park, Joong, Lee, Jung Chan, Kim, Hee Chan
Format: Article
Language:English
Subjects:
3D spheroid
Adipose Tissue - cytology
cell aggregation
Cell Culture Techniques - methods
Cell Survival
Cells, Cultured
centrifugal force
centrifugal microfluidic systems
Centrifugation
Coculture Techniques
Cytokines - metabolism
Diffusion
Dimethylpolysiloxanes - chemistry
Fibroblasts - cytology
Fibroblasts - metabolism
Humans
Hypergravity
lab-on-a-CD
Lung - cytology
Microfluidics - instrumentation
Microfluidics - methods
Spheroids, Cellular - cytology
Spheroids, Cellular - metabolism
Stem Cells - cytology
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Summary:In living tissue, cells exist in three-dimensional (3D) microenvironments with intricate cell-cell interactions. To model these cellular environments, numerous techniques for generating cell spheroids have been proposed and improved. However, previously reported methods still have limitations in uniformity, reproducibility, scalability, throughput, etc. Here, we present a centrifugal microfluidic-based spheroid (CMS) formation method for generating both co-culture and mono-culture 3D spheroids in a highly controlled manner. We designed circularly arrayed microwells to allow the even distribution of cells introduced at the center of a rotating platform and to provide identical hypergravity conditions at each well by the centrifugal forces generated. Compared with conventional well plate-based spheroid formation, the CMS formation method significantly promotes sphericity and consistency in both size and shape with high production yields. In addition to mono-culture spheroids, we successfully generated co-culture spheroids in concentric, Janus, and sandwich shapes using human adipose-derived stem cells and human lung fibroblasts, demonstrating the versatility of our CMS formation method. We believe that our new method for generating 3D spheroids will become one of the essential technologies in the field of 3D cell culture. We also expect that we are providing an innovative means to assess cellular responses, including cell motility under different hypergravity conditions.
ISSN:1758-5090
1758-5090
DOI:10.1088/1758-5090/aa9472