Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Solid support and method of culturing cells on said solid...
Reexamination Certificate
1999-06-23
2001-10-16
Naff, David M. (Department: 1651)
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
Solid support and method of culturing cells on said solid...
C435S177000, C435S180000, C435S396000, C435S397000, C435S401000, C435S262500
Reexamination Certificate
active
06303375
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to a cell supporting matrix for supporting cells, a cell culture device and a fluid treating device wherein such cell supporting matrix is used.
Cell cultivation has been conducted by known processes such as those utilizing microcarriers, hollow fibers, porous matrices, and microcapsules.
Among these, attention has focused on the cell culture process wherein a cell suspension is injected into a matrix having a three dimensional porous structure and to the process wherein such matrix is impregnated with the cell suspension for immobilization and culturing of the cells.
In the perfusion culture utilizing such cell supporting matrix, flow paths for the liquid culture medium are necessary, and various improvements have been disclosed. Exemplary such improvements include provision of capillaries having a diameter of 1.5 mm at an interval of 3 mm in the matrix as disclosed in Ijima et al., Artificial Organs vol. 23, page 463, 1994 (in Japanese) and use of some matrices in the form of 2 mm cubic blocks as disclosed in Ohshima et al., Artificial Organs, vol. 21, page 1169, 1997.
When cell seeding by plain sedimentation precipitation is conducted by such methods, percentage of the cells immobilized is extremely low in the range of 10 to 30%, and efficient cell immobilization is not realized by such processes. Such processes, therefore, have proved impractical.
An improvement has been proposed wherein the matrix filled with the cells is subsequently subjected to centrifugation so that the cells may move in the matrix in the exterior direction, and the percentage of the cells immobilized has been thereby increased. In this process, the percentage of the cells immobilized has been increased to 80%.
This process, however, is impractical since a prolonged period as well as troublesome handling are required before the cell immobilization.
As described above, no technique has been so far provided which is capable of immobilizing and culturing the cells at a high density in a simple, efficient manner and in a short period.
SUMMARY OF THE INVENTION
In view of such situation, an object of the present invention is to provide a cell supporting matrix which is capable of efficiently supporting the cells at a high density in a short period. Another object of the invention is to provide a cell culture device and a fluid treating device utilizing such cell supporting matrix.
Such objects of the invention are achieved by the present invention according to (1) to (17), below.
(1) A cell supporting matrix for supporting cells, said cell supporting matrix having formed therein
a plurality of large pores, and
a plurality of communicating pores whose pore size decreases from one surface of the cell supporting matrix and from interior surface of said pore to the interior of the cell supporting matrix.
(2) A cell supporting matrix according to the above (1) wherein said communicating pores have a pore size ranging from below to beyond the cell size of the cells to be immobilized in the cell supporting matrix.
(3) A cell supporting matrix for immobilizing cells wherein
said cell supporting matrix has a plurality of large pores and a plurality of communicating pores formed therein, and
said communicating pores have a pore size ranging from below to beyond the size of the cells to be immobilized in the cell supporting matrix.
(4) A cell supporting matrix according to any one of the above (1) to (3) wherein said large pores include pores which open at said one surface of the cell supporting matrix.
(5) A cell supporting matrix according to any one of the above (1) to (4) wherein said large pores have finger-like structure.
(6) A cell supporting matrix according to any one of the above (1) to (5) wherein said macro pores have an average pore size in the range of from 100 to 1000 &mgr;m.
(7) A cell supporting matrix according to any one of the above (1) to (6) wherein said communicating pores have an average pore size in the range of from 5 to 100 &mgr;m.
(8) A cell supporting matrix according to any one of the above (1) to (7) wherein said communicating pores has have a maximum pore size in the range of from 30 to 200 &mgr;m.
(9) A cell supporting matrix according to any one of the above (1) to (8) wherein said communicating pores have a minimum pore size in the range of from 0.1 to 10 &mgr;m.
(10) A cell supporting matrix according to any one of the above (1) to (9) wherein said cell supporting matrix further comprises a porous skin layer on the surface other than said one surface wherein said large pores have their opening.
(11) A cell supporting matrix according to any one of the above (1) to (10) wherein said skin layer has an average pore size smaller than said average pore size of said communicating pores.
(12) A cell supporting matrix according to any one of the above (1) to (11) wherein said matrix has elasticity.
(13) A cell supporting matrix according to any one of the above (1) to (12) wherein said cell is an animal cell.
(14) A cell culture device which has the cell supporting matrix of any one of the above (1) to (13), and wherein the cells are immobilized and cultured in said cell supporting matrix.
(15) A cell culture device according to the above (14) wherein said device has a faculty for recovering the product from said cells.
(16) A fluid treating device which has the cell supporting matrix of any one of the above (1) to (13), and wherein said device is used by passing a fluid through said cell supporting matrix and treating the fluid by utilizing the metabolic or biosynthetic function of the cells supported on said cell supporting matrix.
(17) A fluid treating device according to the above (16) wherein said device functions as a bioartificial liver.
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Kimura Tetsuhiro
Omura Yoshitaka
Tokunaga Norifumi
Burns Doane , Swecker, Mathis LLP
Naff David M.
Terumo Kabushiki Kaisha
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