Title | Microfluidic hydrodynamic cellular patterning for systematic formation of co-culture spheroids. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Torisawa Y-S, Mosadegh B, Luker GD, Morell M, K O'Shea S, Takayama S |
Journal | Integr Biol (Camb) |
Volume | 1 |
Issue | 11-12 |
Pagination | 649-54 |
Date Published | 2009 Dec |
ISSN | 1757-9708 |
Keywords | Animals, Cell Differentiation, Coculture Techniques, Embryonic Stem Cells, Hep G2 Cells, Mice, Microfluidic Analytical Techniques, Microscopy, Fluorescence, Spheroids, Cellular |
Abstract | This paper describes a microfluidic method to form co-culture spheroids of various geometries and compositions in order to manipulate cell-cell interaction dynamics. The cellular patterning is performed in a two-layered microfluidic device that sandwiches a semi-porous membrane so that flow occurs from the top channel through the membrane to the bottom channel. Arbitrary cellular arrangements are enabled by regulating the geometric features of the bottom channel so that as culture media drains, the flow hydrodynamically focuses (aggregates) cells onto the membrane only over the regions of the bottom channel. Furthermore, when the top channel has multiple inlets, cells can be seeded in adjacent laminar streams, allowing different cell types to be patterned simultaneously in well defined spatial arrangements. Interestingly, the initial cell positioning of certain cell types can result in two juxtaposed non-concentric "Janus" spheroids, rather than homogeneous mixtures or layered shell structures. Therefore, the initial position of cells prior to aggregation can influence the final configuration within a co-culture spheroid. When Janus spheroids were constructed from mouse embryonic stem (mES) cells and hepatocytes, the mES cells differentiated in a spatially distinct pattern dictated by the position of the hepatocytes. This contrasts with uniform mES differentiation observed when co-culture spheroids are formed by the conventional method of randomly mixing the two cell types. This cellular patterning method opens new possibilities for understanding and manipulating interactions between different cell types in 3D. |
DOI | 10.1039/b915965g |
Alternate Journal | Integr Biol (Camb) |
PubMed ID | 20027373 |
PubMed Central ID | PMC2825702 |
Grant List | R01CA136553 / CA / NCI NIH HHS / United States R01 HL084370-04 / HL / NHLBI NIH HHS / United States HL-084370 / HL / NHLBI NIH HHS / United States 1R01CA136829 / CA / NCI NIH HHS / United States NS-048187 / NS / NINDS NIH HHS / United States GM-06695 / GM / NIGMS NIH HHS / United States R01 HL084370 / HL / NHLBI NIH HHS / United States R01 CA136553 / CA / NCI NIH HHS / United States P50CA093990 / CA / NCI NIH HHS / United States P50 CA093990 / CA / NCI NIH HHS / United States R01 NS048187 / NS / NINDS NIH HHS / United States R01 CA136829 / CA / NCI NIH HHS / United States |
Related Institute:
Dalio Institute of Cardiovascular Imaging (Dalio ICI)