Culture device, culture method and cultured organ produced by the culture method

Abstract

A culture device and a culture method by which a substance to be cultured can be three-dimensionally cultured, and the substance thus cultured can be removed as an integrated product with multiple tubes; and a cultured organ produced by the culture method. The culture device comprises a sealed container (2) which contains the substance to be cultured (A) and is disassembled after the culture is completed; multiple ducts (3, 4, 5) arranged in the sealed container (2) and have micropore formed on the outer peripheral surface; a culture medium-feeding device (6, 7) for feeding/circulating the culture medium (B) to at least one duct (3 or 5); an excretory device (8) connected to at least one duct (4) for excreting the waste product (C) permeating into the duct (4) through the micropore of the duct (4) from the substance to be cultured to the outside of the sealed container.

1 - 10 . (canceled) 
     
     
         11 . A cultured organ made to be provided in an organism as an organ of the organism and comprising an integrated product comprising a cultured product of a substance to be cultured and multiple ducts each of which has a plurality of micropores formed on an outer peripheral surface;
 wherein the multiple ducts comprise at least one first duct made to be inosculated with a blood vessel of the organ in the organism and at least one second duct made to be inosculated with an excretory duct of the organ in the organism;   wherein each of the first and second ducts is branched into a plurality of small diameter ducts in the cultured organ, each of the small diameter ducts having the micropores formed on the outer peripheral surface;   wherein a structure approximated to blood vessels in the organ in the organism in which the cultured organ is provided is three-dimensionally reproduced by the at least one first duct by configuring the following: the number, mean diameter of the micropores, and quality of material of the first duct; and the number, diameter, way of branching, and arrangement of the small diameter ducts of the first duct; and   wherein another structure approximated to excretory ducts in the organ in the organism in which the cultured organ is provided is three-dimensionally reproduced by the at least one second duct by configuring the following: the number, mean diameter of the micropores, and quality of material of the second duct; and the number, diameter, way of branching, and arrangement of the small diameter ducts of the second duct.   
     
     
         12 . The cultured organ according to  claim 11 , wherein a plurality of the first ducts is provided to be made to be inosculated with blood vessels or blood and lymphatic vessels of the organ in the organism, and a structure approximated to blood vessels or blood and lymphatic vessels in the organ in the organism in which the cultured organ is provided is three-dimensionally reproduced by the plurality of first ducts by configuring the following: the number, mean diameter of the micropores, and quality of material of the first ducts; and the number, diameter, way of branching, and arrangement of the small diameter ducts of each of the first ducts. 
     
     
         13 . The cultured organ according to  claim 12 ,
 wherein the cultured organ is used as a liver in the organism,   wherein the substance to be cultured is liver cells,   wherein the plurality of first ducts are respectively made to be inosculated with a hepatic artery, a portal vein, and a hepatic vein of the liver in the organism, and the at least one second duct is made to be inosculated with a bile duct of the liver in the organism, and   wherein a structure approximated to the hepatic artery, the portal vein, and the hepatic vein in the liver in the organism in which the cultured organ is provided is three-dimensionally reproduced by the plurality of first ducts, and another structure approximated to bile ducts in the liver in the organism in which the cultured organ is provided is three-dimensionally reproduced by the at least one second duct.   
     
     
         14 . The cultured organ according to  claim 12 ,
 wherein the cultured organ is used as a pancreas in the organism,   wherein the plurality of first ducts are respectively made to be inosculated with blood vessels in the pancreas in the organism, and the at least one second duct is made to be inosculated with an excretory duct of the pancreas connecting the pancreas with a gastrointestinal tract in the organism, and   wherein a structure approximated to the blood vessels of the pancreas in the organism in which the cultured organ is provided is three-dimensionally reproduced by the plurality of first ducts, and another structure approximated to excretory ducts of the pancreas connecting the pancreas with a gastrointestinal tract in the organism in which the cultured organ is provided is three-dimensionally reproduced by the at least one second duct.   
     
     
         15 . The cultured organ according to  claim 11 ,
 wherein the cultured organ is produced by culturing three-dimensionally the substance to be cultured by using a culture device comprising a sealed container, wherein the sealed container is for containing the substance to be cultured and has a sealable input port for charging the substance to be cultured and multiple ducts which are arranged in the sealed container and each of which has a plurality of micropores formed on an outer peripheral surface, wherein the multiple ducts of the culture device comprise at least one culture medium-feeding duct for feeding or circulating a culture medium and at least one excretory duct for exhausting a waste product, and wherein the first duct of the cultured organ is originated from the culture medium-feeding duct of the culture device and the second duct of the cultured organ is originated from the excretory duct of the culture device,   wherein the culture device further comprises:
 a culture medium-feeding device connected with the culture medium-feeding duct, wherein the culture medium-feeding device comprises a culture medium circulation circuit for feeding or circulating the culture medium to the culture medium-feeding duct, which is connected to both ends of the culture medium-feeding duct, a pump for circulating the culture medium, which is arranged in the culture medium circulation circuit, and a control box for controlling the circulating culture medium, which is arranged in the culture medium circulation circuit; 
 an excretory device connected with the excretory duct for exhausting waste product permeating into the excretory duct from the substance to be cultured through the micropores of the excretory duct to the outside of the sealed container, wherein the excretory device comprises a waste product-containing vessel arranged in the outside of the sealed container, and a sending duct for sending the waste product accumulating within the excretory duct to the waste product-containing vessel; and 
 at least one partition wall which is arranged in the sealed container so as to divide an inner space of the sealed container into multiple cells and is formed with multiple small holes, the multiple ducts being inserted into some of the multiple small holes in the at least one partition wall so as to be held, and remaining multiple small holes in the at least one partition wall allowing both of the substance to be cultured and the culture medium to migrate between respective cells, 
 wherein the culture medium-feeding duct is branched into a plurality of small diameter ducts in the sealed container, each of the small diameter ducts having the micropores formed on the outer peripheral surface, and the small diameter ducts of the culture medium-feeding duct are respectively inserted into the multiple small holes in the at least one partition wall, 
 wherein the excretory duct is branched into a plurality of small diameter ducts in the sealed container, each of the small diameter ducts having the micropores formed on the outer peripheral surface, and the small diameter ducts of the excretory duct are respectively inserted into the multiple small holes in the at least one partition wall, 
 wherein the culture medium-feeding duct is made to reproduce three-dimensionally a structure approximated to blood vessels in an organ in an organism in which the cultured organ is provided, by configuring the following: the number, mean diameter of the micropores, and quality of material of the culture medium-feeding duct; the number, diameter, way of branching, and arrangement of the small diameter ducts of the culture medium-feeding duct; and arrangement of the multiple small holes for the small diameter ducts of the culture medium-feeding duct in the at least one partition wall, 
 wherein the excretory duct is branched into a plurality of small diameter ducts in the sealed container, each of the small diameter ducts having the micropores formed on the outer peripheral surface, and the small diameter ducts of the excretory duct are respectively inserted into the multiple small holes in the at least one partition wall, 
 wherein the excretory duct is made to reproduce three-dimensionally a structure approximated to excretory ducts in the organ in the organism in which the cultured organ is provided, by configuring the following: the number, mean diameter of the micropores, and quality of material of the excretory duct of the culture device; the number, diameter, way of branching, and arrangement of the small diameter ducts of the excretory duct; and arrangement of the multiple small holes for the small diameter ducts of the excretory duct in the at least one partition wall, and 
 wherein the cultured organ is produced by culturing three-dimensionally the substance to be cultured in the sealed container, while the culture medium is fed to the sealed container through the culture medium-feeding duct by the culture medium-feeding device and the waste product of the substance to be cultured is exhausted to the outside of the sealed container through the excretory duct and the excretory device, while holding the substance to be cultured in the sealed container. 
   
     
     
         16 . The cultured organ according to  claim 12 ,
 wherein the cultured organ is produced by culturing three-dimensionally the substance to be cultured by using a culture device comprising a sealed container, wherein the sealed container is for containing the substance to be cultured and has a sealable input port for charging the substance to be cultured and multiple ducts which are arranged in the sealed container and each of which has a plurality of micropores formed on an outer peripheral surface, wherein the multiple ducts of the culture device comprise a plurality of culture medium-feeding ducts for feeding or circulating a culture medium and at least one excretory duct for exhausting a waste product, and wherein the plurality of first ducts of the cultured organ is originated from the plurality of culture medium-feeding ducts of the culture device and the second duct of the cultured organ is originated from the excretory duct of the culture device;   wherein the culture device further comprises:
 culture medium-feeding devices respectively connected with the culture medium-feeding ducts, wherein each of the culture medium-feeding devices comprises a culture medium circulation circuit for feeding or circulating the culture medium to the corresponding culture medium-feeding duct, which is connected to both ends of the corresponding culture medium-feeding duct, a pump for circulating the culture medium, which is arranged in the culture medium circulation circuit, and a control box for controlling the circulating culture medium, which is arranged in the culture medium circulation circuit, and wherein the culture medium circulating in each of the culture medium-feeding ducts is the same or are different from the culture medium circulating in another of the culture medium-feeding ducts; 
 an excretory device connected with the excretory duct for exhausting waste product permeating into the excretory duct from the substance to be cultured through the micropores of the excretory duct to the outside of the sealed container, wherein the excretory device comprises a waste product-containing vessel arranged in the outside of the sealed container, and a sending duct for sending the waste product accumulating within the excretory duct to the waste product-containing vessel; and 
 at least one partition wall which is arranged in the sealed container so as to divide an inner space of the sealed container into multiple cells and is formed with multiple small holes, the multiple ducts being inserted into some of the multiple small holes in the at least one partition wall so as to be held, and remaining multiple small holes in the at least one partition wall allowing both of the substance to be cultured and the culture medium to migrate between respective cells; 
 wherein each of the culture medium-feeding ducts is branched into a plurality of small diameter ducts in the sealed container, each of the small diameter ducts having the micropores formed on the outer peripheral surface, and the small diameter ducts of each of the culture medium-feeding ducts are respectively inserted into the multiple small holes in the at least one partition wall; 
 wherein the excretory duct is branched into a plurality of small diameter ducts in the sealed container, each of the small diameter ducts having the micropores formed on the outer peripheral surface, and the small diameter ducts of the excretory duct are respectively inserted into the multiple small holes in the at least one partition wall; 
 wherein the plurality of culture medium-feeding ducts is made to reproduce three-dimensionally a structure approximated to blood vessels or blood and lymphatic vessels in an organ in an organism in which the cultured organ is provided, by configuring the following: the number, mean diameter of the micropores, and quality of material of the culture medium-feeding ducts; the number, diameter, way of branching, and arrangement of the small diameter ducts of each of the culture medium-feeding ducts; and arrangement of the multiple small holes for the small diameter ducts of each of the culture medium-feeding ducts in the at least one partition wall; 
 wherein the excretory duct is branched into a plurality of small diameter ducts in the sealed container, each of the small diameter ducts having the micropores formed on the outer peripheral surface, and the small diameter ducts of the excretory duct are respectively inserted into the multiple small holes in the at least one partition wall; and 
 wherein the excretory duct is made to reproduce three-dimensionally a structure approximated to excretory ducts in the organ in the organism in which the cultured organ is provided, by configuring the following: the number, mean diameter of the micropores, and quality of material of the excretory duct of the culture device; the number, diameter, way of branching, and arrangement of the small diameter ducts of the excretory duct; and arrangement of the multiple small holes for the small diameter ducts of the excretory duct in the at least one partition wall; and 
   wherein the cultured organ is produced by culturing three-dimensionally the substance to be cultured in the sealed container, while the culture medium is fed to the sealed container through each of the culture medium-feeding ducts by a respective culture medium-feeding device and the waste product of the substance to be cultured is exhausted to the outside of the sealed container through the excretory duct and the excretory device, while holding the substance to be cultured in the sealed container.   
     
     
         17 . The cultured organ according to  claim 15 ,
 wherein the cultured organ consists of the integrated product which is obtained by three-dimensionally culturing the substance to be cultured in the sealed container of the culture device in a state that the sealed container containing the substance to be cultured is embedded in the organism and the culture medium-feeding device and the excretory device are arranged in the outside of the organism, and which is comprised of the three-dimensionally cultured product of the substance to be cultured and the multiple ducts, and   wherein the integrated product is left with the sealed container in the organism as the organ of the organism.   
     
     
         18 . The cultured organ according to  claim 15 ,
 wherein the sealed container of the culture device is made to be disassembled after culture by cutting at an optional place, or is formed with multiple divided bodies so as to be disassembled after culture,   wherein the cultured organ consists of the integrated product which is taken from the sealed container as the integrated product comprising the three-dimensionally cultured product of the substance to be cultured and the multiple ducts by disassembling the sealed container after the culture is completed, and   wherein the integrated product is implanted into the organism as the organ of the organism.   
     
     
         19 . The cultured organ according to  claim 16 ,
 wherein the cultured organ consists of the integrated product which is obtained by three-dimensionally culturing the substance to be cultured in the sealed container of the culture device in a state that the sealed container containing the substance to be cultured is embedded in the organism and the culture medium-feeding device and the excretory device are arranged in the outside of the organism, and which is comprised of the three-dimensionally cultured product of the substance to be cultured and the multiple ducts, and   wherein the integrated product is left with the sealed container in the organism as the organ of the organism.   
     
     
         20 . The cultured organ according to  claim 16 ,
 wherein the sealed container of the culture device is made to be disassembled after culture by cutting at an optional place, or is formed with multiple divided bodies so as to be disassembled after culture,   wherein the cultured organ consists of the integrated product which is taken from the sealed container as the integrated product comprising the three-dimensionally cultured product of the substance to be cultured and the multiple ducts by disassembling the sealed container after the culture is completed, and   wherein the integrated product is implanted into the organism as the organ of the organism.   
     
     
         21 . The cultured organ according to  claim 11 , wherein at least one of the multiple ducts is at least partially formed by semipermeable membrane, unglazed cylindrical body, or blood vessel prosthesis. 
     
     
         22 . The cultured organ according to  claim 11 , wherein the plurality of micropores of each of the multiple ducts have a mean diameter of 100 to 10,000 Å. 
     
     
         23 . The cultured organ according to  claim 17 , wherein the sealed container is at least partially formed by a clear material. 
     
     
         24 . The cultured organ according to  claim 17 , wherein the sealed container is in a form of a capsule comprising a cylindrical part and a pair of hemispheres respectively connected to both ends of the cylindrical part. 
     
     
         25 . The cultured organ according to  claim 17 , wherein the sealed container is formed by synthetic resin having flexibility, biomaterial having compatibility to the organism, or material able to melt after a predetermined period in the organism. 
     
     
         26 . The cultured organ according to  claim 19 , wherein the sealed container is at least partially formed by a clear material. 
     
     
         27 . The cultured organ according to  claim 19 , wherein the sealed container is in a form of a capsule comprising a cylindrical part and a pair of hemispheres respectively connected to both ends of the cylindrical part. 
     
     
         28 . The cultured organ according to  claim 19 , wherein the sealed container is formed by synthetic resin having flexibility, biomaterial having compatibility to the organism, or material able to melt after a predetermined period in the organism.