WO2004005455A1 - Support de culture cellulaire et unite de culture cellulaire - Google Patents

Support de culture cellulaire et unite de culture cellulaire Download PDF

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Publication number
WO2004005455A1
WO2004005455A1 PCT/JP2003/008472 JP0308472W WO2004005455A1 WO 2004005455 A1 WO2004005455 A1 WO 2004005455A1 JP 0308472 W JP0308472 W JP 0308472W WO 2004005455 A1 WO2004005455 A1 WO 2004005455A1
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WO
WIPO (PCT)
Prior art keywords
carrier
cell culture
porous
cell
cylindrical
Prior art date
Application number
PCT/JP2003/008472
Other languages
English (en)
Japanese (ja)
Inventor
Yoichi Ishikawa
Original Assignee
Able Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Able Corporation filed Critical Able Corporation
Priority to AU2003246257A priority Critical patent/AU2003246257A1/en
Publication of WO2004005455A1 publication Critical patent/WO2004005455A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/02—Membranes; Filters

Definitions

  • the present invention relates to a cell culture carrier and a cell culture device, and more particularly, to a cell culture carrier effective for rapidly, uniformly and densely culturing animal cells in a carrier, a method for producing the same, and a cell culture device.
  • cell modules that carry cultured cells, especially animal cells can be effectively used in many fields such as production of useful substances, safety evaluation of foods and drugs, artificial organs and tissues, and pharmacology. . Background art
  • a cell culture reactor cylindrical large and small nets are arranged in double, and the space surrounded by them is filled with particulate porous cell carriers, and the center from the outer side of the large mesh
  • a reactor has been put into practical use in which a culture solution flows in a reverse radial direction toward the reactor.
  • This reactor is an excellent reactor capable of uniformly supplying a culture solution to cells growing inside the carrier, on the surface of the carrier, or in the space between the carriers, if the particulate carrier is uniformly and closely packed.
  • the present invention has been made in view of the above-mentioned problems of the conventional technology, and does not require a double-placed cylindrical net for accommodating a carrier, does not require an operation of filling the carrier, and provides an animal. It is an object of the present invention to provide a cell culture device capable of culturing cells rapidly, homogeneously and at high density, and observing a carrier during culturing, a cell culture carrier and a cell module on which cells are formed.
  • the present inventors have conducted intensive studies in order to solve the above problems, and as a result, if a porous carrier having a predetermined shape and properties is formed in a cylindrical block in advance, there is no need to fill a granular carrier, The inventors have found that the problem can be solved, and have completed the present invention.
  • the first cell culture device of the present invention comprises a porous and cylindrical cell culture carrier containing a hard material (excluding hydroxy and hydroxyapatite) and Z or a soft material as a carrier material.
  • a porous and cylindrical cell culture carrier containing a hard material (excluding hydroxy and hydroxyapatite) and Z or a soft material as a carrier material.
  • a cylindrical envelope surrounding the cylindrical carrier through a space; and a culture solution distribution means for flowing the culture solution from the space through the outer peripheral wall surface of the cylindrical carrier toward the center.
  • the hard material is at least one kind of porous or non-porous material selected from the group consisting of metal, glass and ceramics. If the soft material is porous or non-porous Characterized in that it is a polymer material of
  • first cell culture device of the present invention is characterized in that the hard material and the Z or soft material are in the form of beads having a particle diameter of 100 to 100 x m.
  • the cell culture carrier of the present invention contains a carrier material and a cell growth promoting agent, and is characterized by being porous and cylindrical.
  • the cell growth promoting agent is a polymer-based adhesive, specifically, polyvinyl acetate, polyvinyl alcohol, silicone rubber, natural rubber, and rubber. At least one member selected from the group consisting of loprene rubber, vinyl resin, epoxy resin, phenolic resin, urethane resin, unsaturated polyester, cellulose, protein, starch, sugar, lipid, collagen and derivatives thereof It is characterized by the following.
  • the carrier material is a porous or non-porous hard material and Z or a soft material.
  • the hard material is metal, glass and At least one kind of porous or non-porous material selected from the group consisting of ceramics, and the soft material is a porous or non-porous polymer material.
  • Still another preferred embodiment of the carrier for cell culture of the present invention is characterized in that the carrier material is in the form of beads of 100 to 100 ⁇ .
  • the beads of the carrier material are porous and have continuous pores having an opening diameter of 50 ⁇ or less.
  • Another method for producing the cell culture carrier of the present invention includes the steps of:
  • porous or non-porous hard and / or soft material beads are formed into a cylindrical shape by contacting the above-mentioned liquid in which the cell growth agent is dissolved or suspended, and then formed into a cylindrical shape. Drying the body.
  • the second cell culture device of the present invention is a cell culture device using the cell culture carrier as described above,
  • This cell culture carrier a cylindrical envelope surrounding the carrier via a space, and a culture solution flowing means for flowing a culture solution from the space through the outer peripheral wall surface of the carrier toward the center. It is characterized by having.
  • the porosity of the peripheral wall of the carrier is 30 to 85 V o 1 ° / 0 .
  • another preferred embodiment of the second cell culture device of the present invention is characterized in that an outer peripheral wall and / or an inner peripheral wall of the carrier is coated with a porous layer having a larger pressure loss than the peripheral wall. I do.
  • the cell module of the present invention is characterized in that animal cells are formed on the cell culture carrier in the first cell culture device as described above or on the cell culture carrier as described above.
  • a preferred embodiment of the cell module of the present invention is characterized in that the above-mentioned animal cells are formed using the first cell culture device or the second cell culture device as described above.
  • porous carrier has an integral structure, the handling of the carrier after cell culture is improved.
  • the cell culture carrier of the present invention has a predetermined cell growth promoting agent added thereto, the growth and growth of the target cells can be further accelerated and accelerated. Since it can function as a binder for the carrier material, it is also effective when imparting a predetermined shape to the cell culture carrier of the present invention.
  • a transparent cylindrical envelope surrounding the outer peripheral wall of the carrier through a space is arranged. If the culture solution is supplied in a reverse radial direction (radially toward the center), the outer peripheral wall surface of the carrier can be visually recognized, and the culture state can be observed.
  • the cell culture device of the present invention includes the first cell culture device and the second cell culture device, but has basically the same configuration except that the cell culture carrier used is different.
  • the cylindrical envelope used in the first and second cell culture devices may be any as long as it can surround or store a cell culture carrier in a cylindrical shape, typically a donut shape, through a space. Examples include a housing, a cylindrical container, and a cylindrical tank. During cell culture, a cell culture solution is filled in the space.
  • the culture solution flowing means used in the first and second cell culture devices has a function of flowing the culture solution filled in the space through the peripheral wall of the cylindrical cell culture carrier and into the inside of the cylinder. If you have + minutes, various pumping or Can be exemplified by a suction pump.
  • the cell culture carrier of the present invention containing a cell adhesion promoting agent is used for the second cell culture device.
  • the difference between the cell culture carrier of the present invention and the cell culture carrier used in the first cell culture device is, in principle, whether or not it contains a cell growth promoting agent.
  • the carrier will be described.
  • first cell culture carrier used in the first cell culture device
  • first cell culture carrier is cylindrical and porous.
  • the porosity is affected by the type of the cells to be cultured and the culture medium (medium), but it is sufficient if the culture medium can be circulated. 30 to 85 vo 1. /. It is sufficient to have a porosity of.
  • the porosity is less than 30%, the carrier volume utilization efficiency is insufficient. If the porosity exceeds 85%, cells may easily flow out or the carrier strength may be insufficient. If the porosity exceeds 85%, the pressure loss will be small, and the culture solution may not flow through the entire carrier but may flow partially.
  • the porosity can be measured by applying a normal bulk density measurement method.
  • the thickness of the peripheral wall is also affected by the type of cells to be cultured and the type of culture medium, but is preferably 2 cm or less. Dissolved oxygen may be insufficient on the downstream side, specifically, near the central cavity of the cylindrical carrier, which is not preferable.
  • the carrier material is roughly classified into a hard material and a soft material. In the present invention, both can be used, and both can be used in combination.
  • Such hard materials refer to various metals, inorganic materials such as glass and ceramics, and soft materials refer to various resins, cellulose, elastomers, and other materials.
  • Such a hard material and a soft material can be used regardless of whether they are porous or non-porous, and a mixture of a porous material and a non-porous material can be used. .
  • a raw material powder or the like may be molded and fired to form a cylindrical porous glass or porous ceramic by a conventionally known method.
  • a cylindrical porous resin molded body may be molded by a so-called foam molding method using various foaming agents, for example, a cylindrical foamed polyurethane resin molded body may be manufactured.
  • a porous resin molded article can be obtained by a pressure blowing method of an inert gas such as nitrogen gas.
  • a non-woven fabric such as a polyester non-woven fabric may be filled in a mold having an appropriate cylindrical cavity, and a binder may be added to the mold to bond the non-woven fabric.
  • a cylindrical body may be created.
  • the carrier may be formed by cutting out a relatively large porous material into a desired shape.
  • the metal beads, glass beads, and ceramic beads are assembled into a cylindrical shape, heated, and the partially melted beads are bound together to form a porous cylinder. Shape the body Can be achieved.
  • the particle size of the beads at this time is not particularly limited, but may be 100 to 10 ⁇ .
  • a porous cylinder can also be obtained by binding metal particles, glass particles, ceramic particles, resin particles, rubber particles, and the like with an appropriate binder.
  • the beads used in such a production method may be porous or non-porous, but porous beads may be more preferable in consideration of the flowability of the culture solution.
  • porous ceramics include silica gel, bentonite, alumina, silica, zeolite, and magnesia.
  • porous beads When porous beads are used, it is preferable to select those having continuous holes with an opening diameter of 50 m or less in order to ensure the flowability of the culture solution. In a pore having an opening diameter of 50 ⁇ m or less, it is easy to secure a flow path of a culture solution because cells hardly proliferate inside the pore.
  • second cell culture carrier the cell culture carrier of the present invention
  • This second cell culture carrier has basically the same configuration as the above-described first cell culture carrier except that it contains a cell growth promoting agent.
  • the carrier material of the second cell culture carrier also includes hydroxyapatite. Hydroxyapatite is also used in artificial bones and dental roots, and has the property of easily adhering cells.
  • the cell adhesion promoting agent is not particularly limited as long as it promotes cell adhesion, and is not particularly limited.
  • examples thereof include a so-called polymer adhesive. That is, high molecular compounds having adhesive properties, for example, poly (vinyl acetate), poly (vinyl alcohol), poly (vinyl chloride), cyanoacrylate.
  • Thermoplastic resins such as polystyrene, polyamide and unsaturated polyester; synthetic resins such as epoxy resin, phenolic resin and urethane resin; rubbers such as natural rubber, nitrile rubber and silicone rubber; cellulose; Mention may be made of starch, sugar, lipid or collagen, and any mixtures thereof.
  • polymer compound not only the above-mentioned compounds and materials themselves, but also various derivatives such as ion-exchange derivatives can be used, and these derivatives can be used in any combination of at least one kind. it can.
  • adhesive polymer compounds are usually dissolved or suspended in an appropriate solvent or in the form of an emulsion, for example, a methanol solution of polyvinyl acetate, an aqueous solution of polyvinyl alcohol, or a rubber paste. It is used in the form of aqueous solutions of emulsion rubber, cellulose, starch, sugar and collagen of black rubber, vinyl resin, epoxy resin, fuanol resin, urethane resin and unsaturated polyester resin.
  • an appropriate solvent or in the form of an emulsion for example, a methanol solution of polyvinyl acetate, an aqueous solution of polyvinyl alcohol, or a rubber paste. It is used in the form of aqueous solutions of emulsion rubber, cellulose, starch, sugar and collagen of black rubber, vinyl resin, epoxy resin, fuanol resin, urethane resin and unsaturated polyester resin.
  • the cell growth promoting agent as described above can be contained in the cell culture medium by a coating method-dipping method.
  • a solution or an emulsion of the cell growth promoter is applied to the surface of the first cell culture carrier, or the first cell culture carrier is immersed in the solution or the emulsion of the cell growth promoter. Further, it may be dried by air drying or hot air drying. In addition, such application and immersion may be repeated not only once but also several times to ensure the content of the cell growth promoter.
  • the second cell culture carrier can also be produced by binding the beads of the above carrier material with the cell growth promoting agent.
  • a carrier material bead is filled into a mold with cylindrical cavity. After that, a solution of the cell growth promoting agent may be poured, or the cell growth promoting solution may be poured into a mold first, filled with carrier material beads, and then dried. By such drying, the solvent contained in the cell adhesion promoter solution or the like is released, so that a porous carrier as a whole can be obtained even if the carrier material beads are non-porous.
  • the present invention in the first and second cell culture carriers, it is possible to coat the outer peripheral wall surface and / or the inner peripheral wall surface with a porous layer having a larger pressure loss than the carrier itself. The effect of uniformly flowing the culture solution through the carrier can be further improved.
  • Such a porous layer having a large pressure loss may be formed by forming a porous pipe having a large pressure loss in advance and bringing a carrier into close contact with the porous pipe, or forming a porous pipe concentric with the carrier in the envelope. It can also be formed by arranging pipes.
  • the cell module of the present invention is obtained by growing animal cells on the first cell culture carrier or the second cell culture carrier described above. Typically, these carriers are cultured in the cell culture device of the present invention. It was done.
  • the first cell culture carrier and the second cell culture carrier, particularly the second cell culture carrier are excellent in the formation and cultivation of animal cells, and the uniformity of porosity, Excellent culture uniformity due to isotropic properties, and excellent handling properties during transport / attachment / detachment due to rigidity.
  • FIG. 1 is a cross-sectional view showing one example of the cell culture reactor of the present invention
  • FIG. 2 is a configuration diagram showing one example of the cell culture system of the present invention. -Best mode for carrying out the invention
  • the present invention will be described in more detail with reference to some examples, but the present invention is not limited to these examples.
  • FIG. 1 is a cross-sectional view showing one example of the cell culture reactor of the present invention.
  • the bottom plate 1 is formed integrally with the central column 2. Further, an integrally formed cylindrical porous carrier block 4 and a glass cylinder 5 are disposed in contact with the elastic sheet 3 disposed on the upper surface of the bottom plate 1, and the elastic sheet 6 and the top plate 7 are disposed in contact with the upper end thereof.
  • the bottom plate 1, the top plate 7, the elastic sheets 3 and 6 and the glass cylinder 5 form a substantially cylindrical envelope. Then, the female screw 9 of the culture solution outlet nozzle 8 is screwed into the male screw 10 formed at the upper end of the column 2 to form the bottom plate 1, the elastic sheets 3 and 6, the porous carrier 4, the glass cylinder 5, and the culture solution. Outlet nozzle 8 is fixed integrally.
  • a culture solution supply nozzle 11 is fixed to the top plate 7 by being sealed with an O-ring 12.
  • the O-ring 13 prevents the culture solution from leaking from the screw portion between the top plate 7 and the culture solution outlet nozzle 8.
  • the glass cylinder 5 and the outer peripheral wall surface of the porous carrier 4 are separated from each other, and a space 14 is formed and communicates with the culture solution supply nozzle 11.
  • the culture solution When the culture solution is supplied from the culture solution supply nozzle 11 by a pump, the culture solution fills the space 14 and flows in the direction of arrow 23 from the outer periphery of the cylindrical carrier 4 in a reverse radial direction to form a hollow portion 2 1 at the center. To reach. A part of the column 2 is thin, from which the culture solution is introduced into the hollow portion 21 in the center of the column 2 through a plurality of lateral holes 22 and discharged from the culture solution outlet nozzle 8.
  • the porous carrier 4 may be made of various hard materials or soft materials. What uses a material as a carrier material can be used.
  • the cell culture carrier of the present invention can be obtained.
  • the cell culture reactor using the cell culture carrier containing the agent corresponds to the second cell culture device of the present invention.
  • porous carrier 4 It is desirable to select an appropriate material for the porous carrier 4 in consideration of the type of the cell, the purpose of the culture, the culture conditions, and the like.
  • FIG. 2 is a configuration diagram showing an example of a culture system using the cell culture reactor of the present invention.
  • a culture medium 33 in a medium adjustment tank 32 is circulated to a reactor 31 in FIG. 1 by a pump 34.
  • the pH, dissolved oxygen, dissolved carbon dioxide, and composition of the culture solution are controlled by ordinary methods. An example of culture using this cell culture device is described below.
  • the cell seeding method includes a method of immersing the porous carrier of the present invention in a cell suspension, and a method of forming a porous carrier into a cell suspension in a closed container. It is possible to adopt a method of immersing and applying a negative pressure to evacuate the air in the carrier and distribute the cells in the carrier.
  • the cells When the cells are seeded on the carrier, the cells are allowed to stand and adhere, and the post-culture solution is allowed to flow, so that the cells are prevented from flowing out of the carrier.
  • the cylindrical porous carrier of the present invention when the culture solution flows from the outer peripheral wall to the center, the flow rate increases near the center and the pressure loss at the center increases, so that the culture solution easily flows uniformly.
  • it has a structure, it is preferable to arrange a porous body having a larger pressure loss than the material constituting the porous carrier on the outer peripheral wall or the inner peripheral wall of the porous carrier in order to flow more uniformly.
  • the porous body arranged on the outer peripheral wall or the inner peripheral wall may be in close contact with the porous carrier, but may be in the flow path through which the culture solution flows even if it does not adhere.
  • the column 2 of the above embodiment may be formed of a dense porous body having a hollow portion. In this case, the side hole 22 is unnecessary.
  • a liquid dispersion layer may be provided in close contact with the outer peripheral wall of the porous carrier or on the outer edge.
  • a porous body or a cylinder having fine holes can be used as the liquid dispersion layer.
  • a vertical hole is formed along the center axis of the porous glass cylinder to form a cylindrical porous carrier, and a porous body having the same shape as the porous carrier 4 of the cell culture reactor shown in Fig. 1 is obtained.
  • Created. A 20% methanol solution of polyacetate butyl was applied to the obtained porous body with a brush and air-dried to obtain a cell culture carrier of this example.
  • the obtained cell culture carrier is installed in the cell culture reactor shown in Fig. 1 and cultured.
  • the culture solution was supplied from the nutrient solution supply nozzle 11
  • the culture solution filled the space 14 and directed from the outer wall surface of the cylindrical porous carrier to the inner wall surface in the direction of arrow 23 (reverse radius direction). It was confirmed that the water flowed into the column 2 via the lateral hole 22 and reached the hollow portion of the column 2, and was further discharged from the culture solution outlet nozzle 8.
  • a cell culture carrier is mounted on a cell culture device, cells to be cultured are inoculated, and if the supply of the culture solution, the flow through the porous carrier, and the discharge can be continuously performed, the cells can be cultured in a large amount. Can be.
  • the established hepatocytes HepG2 were put into a medium adjusting tank, and the obtained cell-containing medium was passed through the cell culture device equipped with the cell culture carrier of Example 3 to seed animal cells.
  • the flow rate of the culture solution was reduced to half and the flow of the culture solution was continued.
  • the cell density can be adjusted to 10 per 1 m 1 of the carrier volume based on the consumption rate of darcos cultured while continuously changing the culture medium.
  • the cell culture carrier reached 8 cells, the cell culture carrier was taken out. As a result, a cell module in which animal cells were grown uniformly and at high density was formed.
  • the circular carrier may be formed by molding a soft material such as expanded polyurethane, cellulose, or by cutting or punching out a large block (block). May be.
  • a porous carrier having a predetermined shape and properties is formed into a block shape in advance. No mesh is required, no operation for filling the carrier is required, animal cells can be cultured quickly, uniformly and at high density, and a cell culture device, a cell culture carrier and cells that can observe the carrier during culture are formed.
  • the cell module can be provided.
  • the cell culture device of the present invention enables co-culture of buoyant or adherent cells / heterologous cells.
  • hepatocytes are responsible for many metabolic functions in vivo
  • the cell module constructed by culturing hepatocytes at high density according to the present invention can be used for substance production, food and drug safety evaluation, and liver function evaluation.
  • it is also effective as a device for replicating viruses by introducing a virus such as hepatitis or its gene into the cells of the module.

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Sustainable Development (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Immunology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne une unité de culture cellulaire, qui comprend un support de culture cellulaire cylindrique, poreux et rigide et comprenant un matériau dur (autre que l'hydroxyapatite) et/ou un matériau souple utilisé comme matériau support; une enveloppe cylindrique entourant le support cylindrique par un espace intermédiaire; et un moyen de circulation d'un liquide de culture pour circuler le liquide de culture de l'espace intermédiaire vers le coeur du support, par l'intermédiaire d'une surface de la paroi circonférentielle du support cylindrique. Le support de culture cellulaire, qui est poreux, rigide et cylindrique, comprend un matériau support et un promoteur de polymérisation de la cellule. Le promoteur de polymérisation de la cellule est un adhésif polymérique.
PCT/JP2003/008472 2002-07-05 2003-07-03 Support de culture cellulaire et unite de culture cellulaire WO2004005455A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003246257A AU2003246257A1 (en) 2002-07-05 2003-07-03 Cell culture carrier and cell culture unit

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002-197007 2002-07-05
JP2002197007 2002-07-05

Publications (1)

Publication Number Publication Date
WO2004005455A1 true WO2004005455A1 (fr) 2004-01-15

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PCT/JP2003/008472 WO2004005455A1 (fr) 2002-07-05 2003-07-03 Support de culture cellulaire et unite de culture cellulaire

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010041988A (ja) * 2008-08-12 2010-02-25 Able Corp 培養リアクター
CN102188752A (zh) * 2011-04-12 2011-09-21 浙江大学 制备骨髓间充质干细胞-管道支架复合物的方法及装置

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06277050A (ja) * 1993-03-26 1994-10-04 Kanegafuchi Chem Ind Co Ltd 動物細胞の固定化物および培養方法
JPH1156343A (ja) * 1997-08-21 1999-03-02 Able Kk 動物細胞培養用固定床リアクター及び細胞の播種方法
JP2002079288A (ja) * 2000-06-27 2002-03-19 Hitachi Chem Co Ltd 連通気泡性の微生物担体
EP1211309A1 (fr) * 1999-08-20 2002-06-05 Miyamura, Tatsuo Procede et appareil de proliferation du virus de l'hepatite

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06277050A (ja) * 1993-03-26 1994-10-04 Kanegafuchi Chem Ind Co Ltd 動物細胞の固定化物および培養方法
JPH1156343A (ja) * 1997-08-21 1999-03-02 Able Kk 動物細胞培養用固定床リアクター及び細胞の播種方法
EP1211309A1 (fr) * 1999-08-20 2002-06-05 Miyamura, Tatsuo Procede et appareil de proliferation du virus de l'hepatite
JP2002079288A (ja) * 2000-06-27 2002-03-19 Hitachi Chem Co Ltd 連通気泡性の微生物担体

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010041988A (ja) * 2008-08-12 2010-02-25 Able Corp 培養リアクター
CN102188752A (zh) * 2011-04-12 2011-09-21 浙江大学 制备骨髓间充质干细胞-管道支架复合物的方法及装置

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