WO2002018535A2 - Bioartificial organ for hosting animal and/or human cells - Google Patents
Bioartificial organ for hosting animal and/or human cells Download PDFInfo
- Publication number
- WO2002018535A2 WO2002018535A2 PCT/EP2001/009906 EP0109906W WO0218535A2 WO 2002018535 A2 WO2002018535 A2 WO 2002018535A2 EP 0109906 W EP0109906 W EP 0109906W WO 0218535 A2 WO0218535 A2 WO 0218535A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- bioartificial organ
- constituted
- organ according
- container body
- cavity
- Prior art date
Links
Classifications
-
- 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
- C12M21/00—Bioreactors or fermenters specially adapted for specific uses
- C12M21/08—Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
-
- 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
- C12M25/10—Hollow fibers or tubes
-
- 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
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/16—Hollow fibers
Definitions
- the present invention relates to a bioartificial organ for hosting animal and/or human cells.
- the intended goal of these studies and of the resulting structural prototypes is the common intent to devise a three-dimensional support being capable of hosting said hepatocytes arranged according to a preset geometry capable of allowing perfusion by the plasma of the patient so that the cultured cells can exchange with said plasma solutes and gases dissolved therein, while preventing the physical passage of the cells, or even of fragments thereof, into said plasma, in order to avoid immunization phenomena.
- the first devices used in the clinical field and intended specifically for liver assistance have used the principle of diffusion and exchange of solutes with different molecular weights through a membrane, drawing this concept directly from dialysis and dialyzers.
- capillary fibers has allowed to optimize the solute exchange and diffusion processes, significantly improving the fluid- dynamics characteristics of bioreactors built with this technique; moreover, the combination of different geometrical structures or of structures having a plurality of microporous capillary bundles has allowed to provide the necessary supply of oxygen, which is essential for cell metabolism.
- a first drawback is the need to achieve effective exchange between the plasma of the patient and the cells contained in the culture device, so that this exchange occurs constantly over the entire exchange surface.
- this exchange is limited by the low pressure at which the plasma or ultrafiltrate, arriving from the patient, is introduced in the device; such low pressure must be maintained in order to avoid submitting the hepatocytes to pressure shocks caused by high supply pressures of the plasma or ultrafiltrate, compromising their vitality and ultimately their functionality.
- a second drawback is the possibility to have an adequate volume of cells, so as to sufficiently replace the hepatic function in the human body; in conventional devices, such volume is very small in relation to their overall dimensions and to the need to assist the hepatic function: in conventional devices, in fact, the useful volume for culture is approximately 1/3 of the total volume of the device, whereas 200 to 300 grams of hepatocytes are necessary in order to support the hepatic functionality of an adult.
- a third drawback is constituted by the fact that the device and the cells cultivated therein must allow perfusion uniformly along the entire extension of the culture, avoiding, as occurs in conventional devices, a concentration of exchange in the inlet region to the detriment of the terminal outlet regions and ultimately a partial utilization of the device. This occurs because conventional devices contain culture supports which are organized randomly in terms of geometry, making it troublesome, as mentioned, to maintain constant perfusion.
- a fourth drawback is that the method of preparing the bioartificial organ must be safe, rapid and repeatable as regards its effectiveness, in order to minimize the time required for clinical use, which is aimed mainly at acute conditions in which the time factor becomes vitally important.
- a fifth drawback resides in that the device must allow a perfusion that prevents any possible passage of cells or fragments thereof into the circulation of the patient. Disclosure of the Invention
- the aim of the present invention is to eliminate the above-noted drawbacks of the prior art by providing a bioartificial organ for hosting animal and/or human cells that solves all the above listed technical drawbacks.
- a bioartificial organ for hosting animal and/or human cells comprising a container body having an internal cavity which can accommodate a cell support and culture structure, said body being provided with at least one inlet port for plasma or ultrafiltrate to be treated drawn from a patient, said inlet port being arranged upstream of said support and culture structure, and with an outlet port for said treated plasma or ultrafiltrate which is arranged downstream of the support and culture structure, characterized in that two end chambers are formed between said structure and said internal cavity, respectively a first chamber for collecting plasma or ultrafiltrate to be treated and a second chamber for collecting treated plasma or ultrafiltrate, said chambers being connected to the outside through said ports, a shaft-like element for coupling said support and culture structure being further provided inside said cavity of the container body and being arranged between the ends of said container body.
- Figure 1 is a schematic sectional view, taken along a longitudinal plane, of the bioartificial organ according to the invention
- Figure 2 is a highly enlarged-scale detail view of a portion of the cell support and culture structure
- Figure 3 is an end view of the cell support and culture structure in the region for coupling to a centered shaft-like element with which the bioartificial organ according to the invention is provided internally;
- Figure 4 is a perspective view, with parts in phantom lines, of a portion of said cell support and culture structure. Ways of carrying out the Invention
- the reference numeral 1 designates a bioartificial organ for hosting animal and/or human cells, which comprises a substantially cylindrical container body 2, having an internal cavity 3 which can accommodate a cell support and culture structure 4.
- the container body 2 is provided with at least one inlet port 5 for plasma or ultrafiltrate drawn from a patient, which is arranged upstream of the structure 4, and with an outlet port 6 for the treated plasma or ultrafiltrate, arranged downstream of the structure 4.
- first chamber 7 for collecting plasma or ultrafiltrate to be treated
- second chamber 8 for collecting treated plasma or ultrafiltrate
- a shaft-like element 9 for the coupling of the structure 4 is also provided which is arranged between the ends of the container body 2; such ends of the container body are constituted by respective hermetic closure caps 10 and 11, in each of which the ports 5 and 6 are formed.
- the cavity 3 also is directly connected to the outside through a second opening 13, which passes through the side wall of the container body 2.
- the cell support and culture structure 4 is constituted by a permeable coil 14 composed of a spiral winding, around the shaft-like element 9, of a multilayer fabric packed in a sandwich-like configuration; the leading edge of said winding is fixed to the shaft-like element 9 so that at least one layer, specified hereinafter, is connected to the axial cavity 9a thereof, while the trailing edge remains in contact with the internal wall of said axial cavity 3 of the container body 2; the coil 14 is embedded in two end containment means 15.
- the fabric composing the coil 14 is composed in a modular fashion of at least six stacked sheet-like layers.
- a first innermost layer is constituted by a first flat ordered arrangement 16 of capillary fibers 17 arranged parallel to the longitudinal axis of said container body 2 and folded in a U-like shape, the free ends of which pass through the respective containment means 15 and lead into the second collection chamber 8.
- a second layer is constituted by a permeable and filtering sheet-like means 18 which is adapted to support the cells.
- a third layer is constituted by a sheet-like grid 19 which is adapted to distribute the cells to be seed.
- a fourth layer is constituted by a second permeable and filtering sheet-like means 20 which is again adapted to support the cells.
- a fifth layer is constituted by a second flat ordered arrangement 21 of capillary fibers 22, which are parallel and opposite to the fibers 17 of the first ordered arrangement 16, are also folded in a U-like shape and have free ends that pass through the respective containment means 15 and lead into the first collection chamber 7.
- a sixth outermost layer is constituted by a separator sheet 23 made of impermeable material.
- the permeable and filtering sheet-like means 18 and the second one 20 are both constituted by sheets of polymeric fabric, preferably polyester, whose weft is woven with a random or ordered arrangement.
- the end containment means 15 are constituted by two rings 24 made of a composite material based on polyurethane and formed snugly transversely inside the cavity 3: the rings form, together with said caps 10 and 11, the first collection chamber 7 and the second collection chamber 8.
- the leading edge of the winding that constitutes the coil 14 is fixed to the shaft-like element 9 after interlocking and gluing in a slotted seat 25 formed along its entire length; the seat 25 has a central portion 25a which is connected, along its entire length, to the axial cavity 9a; the leading edge of the sheet-like distribution grid 19 that constitutes the third layer of the fabric is inserted in the portion 25a.
- each capillary fiber 17 and 22 has a constant diameter and is constituted by a tube-shaped segment of microporous material, preferably polyethersulfone, with pores having diameters between 0.10 and 0.50 microns, and, as mentioned, is folded in a U-like shape substantially at its centerline, so as to form a pair of straight and parallel branches 17a, 22a being directed in mutually opposite directions and so that the ports of the respective free ends match up and lead into a corresponding collection chamber for plasma or ultrafiltrate, the chamber 7 for the fibers 17 and the chamber 8 for the fibers 22.
- microporous material preferably polyethersulfone
- the distribution of the fibers 17 and 22 also is constant along the entire extension of the coil 14.
- the operation of the bioartificial organ according to the invention is as follows: the cells to be supported and cultured are introduced in the bioartificial organ 1 through the opening 12, which conveys them into the axial cavity 9a of the shaft-like element 9.
- the coil 14 is wound in a spiral around the shaft-like element 9 and is fully contained in the axial cavity of the container body 2, firmly retained at its ends by the rings 24 in which said ends are embedded in order to keep said spiral wrapping firm.
- Both rings 24 are crossed only by the ends of the capillary fibers 17 and 22, which converge into the respective chambers for collecting plasma or ultrafiltrate.
- the bioartificial organ 1 can be used on a patient: plasma or the so-called ultrafiltrate is in fact drawn from said patient and introduced in said organ through the port 5 by means of a circuit operating at a low pressure provided by a conventional pumping means and is collected from there in the chamber 7, into which the openings of the ordered arrangement 16 of capillary fibers 17 composing the coil 14 converge.
- the plasma or ultrafiltrate flows through the fibers 17 folded in a U-like arrangement and once it has saturated them it passes through their porous walls, moving with a radial flow towards the layer 18 on which the cells are supported.
- the plasma or ultrafiltrate is purified by contact with the cells, maintaining a flow which is substantially perpendicular to the layers that compose the coil 14 until it reaches the second ordered arrangement 21 of capillary fibers 22, after passing through the next sheet 20 which acts, like the sheet 18, both as a support and as a filter for the cells, in order to prevent any of said cells, or even fragments thereof, from entering the blood circuit of the patient.
- the second opening 13 formed in the lateral wall of the container body 2 allows, during seeding of the cells in the coil 14, the recirculation of the solution that contains them, after connection, by means of a tube provided with a pump (both not shown because of a conventional type), to the opening 12: once seeding has been completed, the opening 12 and the opening 13 are closed by means of convenient plugs.
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Sustainable Development (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Anesthesiology (AREA)
- Cardiology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2001295517A AU2001295517A1 (en) | 2000-09-01 | 2001-08-28 | Bioartificial organ for hosting animal and/or human cells |
EP01976159A EP1313836A2 (en) | 2000-09-01 | 2001-08-28 | Bioartificial organ for hosting animal and/or human cells |
US10/362,601 US20050014250A1 (en) | 2000-09-01 | 2001-08-28 | Bioartificial organ for hosting animal and/or human cells |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMO2000A000182 | 2000-09-01 | ||
IT2000MO000182A IT1316921B1 (en) | 2000-09-01 | 2000-09-01 | BIOARTIFICIAL ORGAN TO HOST ANIMAL AND / OR HUMAN CELLS. |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2002018535A2 true WO2002018535A2 (en) | 2002-03-07 |
WO2002018535A3 WO2002018535A3 (en) | 2002-09-26 |
Family
ID=11450548
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2001/009906 WO2002018535A2 (en) | 2000-09-01 | 2001-08-28 | Bioartificial organ for hosting animal and/or human cells |
Country Status (5)
Country | Link |
---|---|
US (1) | US20050014250A1 (en) |
EP (1) | EP1313836A2 (en) |
AU (1) | AU2001295517A1 (en) |
IT (1) | IT1316921B1 (en) |
WO (1) | WO2002018535A2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1460127A1 (en) * | 2003-03-21 | 2004-09-22 | Rand S.r.l. | Bioreactor, particularly for bioartificial organs |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100886003B1 (en) * | 2007-03-30 | 2009-03-03 | (주)라이프코드 | Bioartificial liver system using bioreactor packed with gel beads |
DE102010016055A1 (en) † | 2010-03-22 | 2011-09-22 | Krones Ag | Device for controlling coils with wound foil material |
BE1024733B1 (en) * | 2016-11-09 | 2018-06-14 | Univercells Sa | CELL GROWTH MATRIX |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5079168A (en) * | 1988-08-10 | 1992-01-07 | Endotronics, Inc. | Cell culture apparatus |
US5786215A (en) * | 1987-05-20 | 1998-07-28 | Baxter International Inc. | Method for culturing animal cells |
EP0909811A2 (en) * | 1997-10-16 | 1999-04-21 | B. BRAUN CAREX S.p.A. | Bioreactor for culturing animal and/or human cells, particularly hepatocytes |
US6242248B1 (en) * | 2000-02-08 | 2001-06-05 | Cedars-Sinai Medical Center | Bioreactor and related method |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4937196A (en) * | 1989-08-18 | 1990-06-26 | Brunswick Corporation | Membrane bioreactor system |
JPH0728722B2 (en) * | 1990-06-29 | 1995-04-05 | 富士写真フイルム株式会社 | Bioreactor equipment |
-
2000
- 2000-09-01 IT IT2000MO000182A patent/IT1316921B1/en active
-
2001
- 2001-08-28 EP EP01976159A patent/EP1313836A2/en not_active Withdrawn
- 2001-08-28 US US10/362,601 patent/US20050014250A1/en not_active Abandoned
- 2001-08-28 WO PCT/EP2001/009906 patent/WO2002018535A2/en not_active Application Discontinuation
- 2001-08-28 AU AU2001295517A patent/AU2001295517A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5786215A (en) * | 1987-05-20 | 1998-07-28 | Baxter International Inc. | Method for culturing animal cells |
US5079168A (en) * | 1988-08-10 | 1992-01-07 | Endotronics, Inc. | Cell culture apparatus |
EP0909811A2 (en) * | 1997-10-16 | 1999-04-21 | B. BRAUN CAREX S.p.A. | Bioreactor for culturing animal and/or human cells, particularly hepatocytes |
US6242248B1 (en) * | 2000-02-08 | 2001-06-05 | Cedars-Sinai Medical Center | Bioreactor and related method |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1460127A1 (en) * | 2003-03-21 | 2004-09-22 | Rand S.r.l. | Bioreactor, particularly for bioartificial organs |
US7371567B2 (en) | 2003-03-21 | 2008-05-13 | Rand S.R.L. | Bioreactor, particularly for bioartificial organs |
Also Published As
Publication number | Publication date |
---|---|
AU2001295517A1 (en) | 2002-03-13 |
IT1316921B1 (en) | 2003-05-13 |
WO2002018535A3 (en) | 2002-09-26 |
US20050014250A1 (en) | 2005-01-20 |
EP1313836A2 (en) | 2003-05-28 |
ITMO20000182A0 (en) | 2000-09-01 |
ITMO20000182A1 (en) | 2002-03-01 |
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