Pathologically relevant tumor microenvironments for high-throughput drug screening
First Claim
1. A three-dimensional biomimetic tumor system comprising:
- a first cell of interest;
a natural or synthetic hydrogel incorporating the first cell of interest, wherein;
the incorporating hydrogel is crosslinked by chemically mediated crosslinking, ionically mediated crosslinking, thermally mediated crosslinking or photocrosslinking,wherein the incorporating hydrogel forms a roughly spherical bead,the value for the elastic modulus of the hydrogel is controlled by the extent of crosslinking of the hydrogel, andthe value for the elastic modulus of the hydrogel is in the range of about E=0.5 kPa to E=100 kPa;
a second cell of interest of different cell type from the first cell of interest, wherein the second cell of interest is dispersed on, attached to, bound to, disposed or coated on the surface of the hydrogel incorporating the first cell of interest.
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Abstract
A three-dimensional cell culture system is provided comprising one or more cell types of interest incorporated in a natural or synthetic hydrogel. An apparatus for high-throughput drug screening is also provided comprising a plurality of three-dimensional cell culture systems and a dispenser for placing at least one three-dimensional cell culture system into a pre-determined well of a multiwell plate. A method for high-throughput drug screening is also provided that comprises providing a test agent, providing a three-dimensional cell culture system, determining a first cellular response of the cell of interest before culturing in the presence of the agent, culturing the cell of interest in the cell culture system in the presence of the agent, determining a second cellular response of the cell of interest after culturing in the presence of the agent, and comparing the first and second cellular responses.
10 Citations
25 Claims
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1. A three-dimensional biomimetic tumor system comprising:
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a first cell of interest; a natural or synthetic hydrogel incorporating the first cell of interest, wherein; the incorporating hydrogel is crosslinked by chemically mediated crosslinking, ionically mediated crosslinking, thermally mediated crosslinking or photocrosslinking, wherein the incorporating hydrogel forms a roughly spherical bead, the value for the elastic modulus of the hydrogel is controlled by the extent of crosslinking of the hydrogel, and the value for the elastic modulus of the hydrogel is in the range of about E=0.5 kPa to E=100 kPa; a second cell of interest of different cell type from the first cell of interest, wherein the second cell of interest is dispersed on, attached to, bound to, disposed or coated on the surface of the hydrogel incorporating the first cell of interest. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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10. A method for making a three-dimensional biomimetic tumor system comprising:
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(a) providing a natural or synthetic hydrogel solution; (b) providing an isolated first cell of interest; (c) suspending the cell in the hydrogel solution; and (d) incorporating the cell in the hydrogel solution by crosslinking the hydrogel, wherein step (d) comprises forming the hydrogel into a roughly spherical bead; and (e) providing an isolated second cell of interest of a different cell type from the first cell of interest; and wherein the second cell of interest is dispersed on, attached to, bound to, disposed or coated on the surface of the hydrogel. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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Specification