Devices and methods for culture of cells
Devices and methods for culture of cells are provided. The devices can comprise a three-dimensional body having multiple two-dimensional surfaces extending inwardly from a periphery of the three-dimensional body towards an interior of the three-dimensional body, wherein the multiple two-dimensional surfaces are configured to support monolayer growth of eukaryotic cells over at least a majority of or all of the surface area of the multiple two-dimensional surfaces.
1. A cell-culture device, comprising:
a three-dimensional body comprising multiple two-dimensional surfaces extending inwardly from a periphery of the three-dimensional body towards an interior of the three-dimensional body, wherein:
(a) the multiple two-dimensional surfaces are configured to support monolayer growth of eukaryotic cells over at least a majority of or all of the surface area of the multiple two-dimensional surfaces;
(b) the multiple two-dimensional surfaces comprise a plurality of ribs extending substantially parallel to one another from the interior of the three-dimensional body towards the periphery of the three-dimensional body, further including a lateral plane extending from a central axis of the three-dimensional body and extending perpendicularly to the plurality of ribs, and wherein the plurality of ribs are spaced from one another by a width that does not exceed the thickness of any one of the plurality of ribs; and
(c) the three-dimensional body has a maximum dimension between 2 mm and 10 mm, wherein the device is substantially spherical, and wherein the maximum dimension is a diameter; or the ratio of the surface area of the multiple two-dimensional surfaces to the volume of the three-dimensional body is between 10 cm 2 /cm 3 and 15 cm 2 /cm 3 .
2. The device of claim 1 , wherein the three-dimensional body comprises at least one of a substantially spherical shape, a substantially ellipsoid shape, and an irregular polyhedral shape.
3. The device of claim 1 , wherein the material forming the multiple two-dimensional surfaces comprises a material selected from at least one of metals, glass, borosilicate, carbon fibers, ceramics, collagen, gelatin, hydrogels, and polymers.
4. The device of claim 1 , wherein the material forming the multiple two-dimensional surfaces comprises at least one polymer, wherein the polymer is:
selected from a polyamide, a polycarbonate, a polysulfone, a polyester, a polyacetal, and polyvinyl chloride.
5. The device of claim 1 , wherein the multiple two-dimensional surfaces further comprise at least one coating selected to facilitate attachment and growth of eukaryotic cells, wherein the at least one coating is selected from a protein and polylysine.
6. The device of claim 1 , wherein the multiple two-dimensional surfaces have been subjected to a plasma surface treatment.
7. The device of claim 1 , wherein the multiple two-dimensional surfaces comprise a modulus and curvature selected to facilitate growth of eukaryotic cells.
8. The device of claim 1 , wherein the eukaryotic cells comprise at least one of stem cells, anchorage dependent cells, mesenchymal cells, and stromal cells.
9. The device of claim 1 , wherein the ratio of the surface area of the multiple two-dimensional surfaces to the volume of the three-dimensional body is between 3 cm 2 /cm 3 and 1,000 cm 2 /cm 3 .
10. The device of claim 1 , wherein the ratio of the surface area of the multiple two-dimensional surfaces to the volume of the three-dimensional body is between 10 cm 2 /cm 3 and 15 cm 2 /cm 3 .
11. The device of claim 1 , wherein the three-dimensional body has a maximum dimension between 2 mm and 10 mm, wherein the device is substantially spherical, and the maximum dimension is a diameter.
12. A cell-culture system, comprising:
a container; and
a group of three-dimensional bodies, each three dimensional body comprising:
multiple two-dimensional surfaces extending inwardly from a periphery of the three-dimensional body towards an interior of each three-dimensional body, wherein:
(a) the multiple two-dimensional surfaces are configured to support monolayer growth of eukaryotic cells over at least a majority of or all of the surface area of the multiple two-dimensional surfaces;
(b) the multiple two-dimensional surfaces comprise a plurality of ribs extending substantially parallel to one another from the interior of the three-dimensional body towards the periphery of the three-dimensional body, further including a lateral plane extending from a central axis of the three-dimensional body and extending perpendicularly to the plurality of ribs, and wherein the plurality of ribs are spaced from one another by a width that does not exceed the thickness of any one of the plurality of ribs; and
(c) the three-dimensional bodies each have: a maximum dimension ranging from 1 mm to 50 mm; or the ratio of the surface area of the multiple two-dimensional surfaces to the volume of the three-dimensional body is between 10 cm 2 /cm 3 and 15 cm 2 /cm 3 .
13. The system of claim 12 , wherein the three-dimensional bodies each have a maximum dimension between 1 mm and 20 mm.
14. The system of claim 12 , wherein the material forming the multiple two-dimensional surfaces comprises at least one polymer, wherein the polymer is selected from a polyamide, a polycarbonate, a polysulfone, a polyester, a polyacetal, and polyvinyl chloride.
15. The system of claim 12 , wherein the multiple two-dimensional surfaces further comprise at least one coating selected to facilitate attachment and growth of eukaryotic cells, wherein the at least one coating is selected from a protein and polylysine.
16. The system of claim 12 , wherein the ratio of the surface area of the multiple two-dimensional surfaces to the volume of the three-dimensional body is between 3 cm 2 /cm 3 and 1,000 cm 2 /cm 3 .
17. A cell-culture system, comprising:
a container; and
a group of three-dimensional bodies, each three dimensional body comprising:
multiple two-dimensional surfaces extending inwardly from a periphery of the three-dimensional body towards an interior of each three-dimensional body, wherein:
(a) the multiple two-dimensional surfaces are configured to support monolayer growth of eukaryotic cells over at least a majority of or all of the surface area of the multiple two-dimensional surfaces, and wherein the multiple two-dimensional surfaces have been subjected to a plasma surface treatment;
(b) the multiple two-dimensional surfaces comprise a plurality of ribs extending substantially parallel to one another from the interior of the three-dimensional body towards the periphery of the three-dimensional body, further including a lateral plane extending from a central axis of the three-dimensional body and extending perpendicularly to the plurality of ribs, and wherein the plurality of ribs are spaced from one another by a width that does not exceed the thickness of any one of the plurality of ribs; and
(c) the three-dimensional bodies each have: a maximum dimension ranging from 1 mm to 50 mm; or a surface area to volume ratio between 3 cm 2 /cm 3 and 1,000 cm 2 /cm 3 .
18. The system of claim 12 , wherein the three-dimensional body has a maximum dimension between 2 mm and 10 mm, wherein the device is substantially spherical, and the maximum dimension is a diameter.
19. A method of culturing cells, comprising:
selecting a group of eukaryotic cells; and
contacting the eukaryotic cells with the at least one three-dimensional body as defined in claim 1 .
20. The method of claim 19 , wherein contacting the eukaryotic cells with the at least one three-dimensional body comprises:
(a) placing the cells and at least one three-dimensional body in a container;
(b) further comprising supplying culture media to the cells; and
(c) further comprising causing movement of the at least one three-dimensional body, wherein causing movement comprises:
(i) rotating or shaking a container in which the at least one three-dimensional body is contained; or
(ii) providing a flow of media into a container in which the at least one three-dimensional body is contained.
21. The method of claim 19 , wherein said at least one three dimensional body is immersed within culture medium inside a suitable container which is configured to resist cellular adhesion.
22. A method of culturing cells, comprising:
selecting a group of eukaryotic cells; and
contacting the eukaryotic cells with the cell-culture system as defined in claim 12 .
23. The system of claim 17 , wherein the ratio of the surface area of the multiple two-dimensional surfaces to the volume of the three-dimensional body is between 10 cm 2 /cm 3 and 15 cm 2 /cm 3 .