WO1999011220A1 - Transplants coated with autologous endothelial cells - Google Patents
Transplants coated with autologous endothelial cells Download PDFInfo
- Publication number
- WO1999011220A1 WO1999011220A1 PCT/SE1998/001549 SE9801549W WO9911220A1 WO 1999011220 A1 WO1999011220 A1 WO 1999011220A1 SE 9801549 W SE9801549 W SE 9801549W WO 9911220 A1 WO9911220 A1 WO 9911220A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cell
- recipient
- endothelial cells
- preparation
- type
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0618—Cells of the nervous system
- C12N5/0619—Neurons
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0676—Pancreatic cells
- C12N5/0677—Three-dimensional culture, tissue culture or organ culture; Encapsulated cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K2035/122—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells for inducing tolerance or supression of immune responses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K2035/126—Immunoprotecting barriers, e.g. jackets, diffusion chambers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/28—Vascular endothelial cells
Definitions
- the present invention refers to a preparation intended to be transmitted to a recipient and including at least one cell from a donor, said cell being of a type producing a substance.
- the invention also refers to a method for producing a preparation intended to be transmitted to a recipient and including at least one cell from a donor, said cell being of a type producing a substance.
- the invention refers to a use of a preparation for treating a disease or deficiency of a recipient by transmitting the preparation, which comprises at least a cell from a donor, to the recipient, said cell being of a type producing a substance, as well as a method for treating a disease or deficiency of a recipient by means of a preparation being transmitted to the recipient and comprising at least one cell from a donor, said 'cell being of a type producing a substance.
- cells which produce active substances or biochemical factors could be transmitted from a donor to a recipient who suffers from deficiency of that substance or factor and to produce that substance or factor in the recipient to reduce said deficiency.
- a treatment is transplantation or transmission of pancreas cells from human beings or, for example, pigs to a patient who suffers from diabetes to increase the insulin production of the patient.
- Other examples are transplantation of cells from the brain, the adrenal glands, the thyroid gland, the liver etc. for treatment of different diseases.
- each individual of an animal or a human being has its own unique immunological identity. It results in that cells or organs may not be transmitted between different individuals without the foreign cells being attacked by the immunological system of the recipient and thereby being killed, or in other words being rejected. Consequently, also the above-mentioned examples of transmission or transplantation of different substance-producing cells can not be done to the extent that would be desirable for the treatment of different diseases.
- the immunological effector cells which cause the rejection of foreign cells mentioned above are mainly bloodborne and normally exist in an inactive state. Activation of these effector cells can be attained in different ways but one quick way is when they are exposed to foreign endothelial cells.
- Endothelial cells are a cell type which in a continuous layer, the so-called the endothelium, completely cover the inside of the blood vessels, the lymphatic system and the heart. The layer is built of a monolayer of cells which together have an extensive surface. Consequently, the endothelial cells are strategical for the immunological effector cells of the recipient to identify and to reject if they are not autologous cells.
- WO96/40887 shows implants of foreign donor cells, as for example pancreas cells in a recipient, said donor cells being provided with an immunological barrier, which is produced, for example, by cartilage.
- the cartilage cells may be taken from the individual who is to receive donor cells but also that it is possible to take cartilage from other individuals.
- the cartilage cells are permitted to culture onto a matrix or some similar substrate so that a continuous layer of cartilage cells is formed.
- the donor cells which are to be inserted into a recipient are added onto this layer of cartilage cells and the layer is then folded over the donor cell in such a manner that a kind of packaging is formed which then is transplanted to a recipient by use of standard surgical techniques.
- WO94/03586 shows a way of detaching cells such as endothelial cells from their substrate.
- the endothelial cells obtained may be used to coat tissue implant or prothesis in order to reduce the rejection when these are inserted into a receiving individual.
- WO94/07432 shows a novel synthetic implant that has a determined porosity. This document point to the possibility to provide endothelial cells onto such a synthetic porous implant.
- the object of the present invention is to provide ways of reducing rejection reactions of a recipient to whom foreign cells are supplied.
- This object is obtained by the preparation initially defined and characterized in that said cell is coated with endothelial cells which are derived from the recipient and which are attached to the surface of said cell in such a way that they form a layer of endothelial cells.
- Such a preparation of cells which are coated with the recipient's own endothelial cells ought to reduce essentially the activation of the immunological effector cells of the recipient and thereby reduce the rejection process. Consequently, it is possible by the preparation according to the invention to transmit or to implant all possible cells from a donor into a patient who suffers from lack of a substance produced by such cells. Accordingly, the invention makes way for a better treatment in the future of diseases or deficiencies that are difficult to treat today.
- endothelial cells of the recipient will, according to the invention, replace the endothelial cells of the donor of said organ.
- the endothelial cells preferably form a monolayer of cells, which covers substantially the whole surface of said cell.
- said cell comprises a type of cell which produces a substance being active with respect to a carrier.
- active substances or biochemical factors is according to the invention hormones.
- hormones may be insulin, growth hormone, thyroid hormone or glucose and mineral ocorticoid.
- said cell may comprise a type of cell, which produces growth factors or a type of cell, which produces transmitter substances, for example dopamine.
- said recipient is a human being or an animal, as well as said donor.
- the preparation is available in form of a solution.
- the preparation may be stored in a suitable way and at the same time be transmitted to a recipient in a simple and conventional way, for example by injection into the bloodstream or the ventricle system of the brain, injection into or supply in any other way to the abdominal cavity, the pleurae, the heart sac or some other tissue.
- the preparation may also comprise several cells in the form of a piece of tissue or a complete new organ. Such a piece of tissue coated with endothelial cells may then be inserted and placed in the body of the recipient by a standard surgical method.
- the object is also obtained by the method initially defined and characterized in that said cell is taken from the donor and is coated with endothelial cells which are derived from the recipient and are permitted to attach to the surface of said cell and form a layer of endothelial cells. Consequently, by such a method it is possible to achieve a preparation which can be transmitted to a patient and which results in a reduced risk of rejection of the preparation.
- a number of endothelial cells are removed from the recipient and are cultured until a sufficient amount is available.
- the cultured number of endothelial cells can be dissolved in a liquid and be poured onto said cell to be coated in such a way that a one-cell- layer of endothelial cells are formed, which covers substantially the whole surface of said cell.
- Said number of endothelial cells may be removed from the recipient by removing a piece of tissue from the recipient and by detaching the endothelial cells from this tissue by adding an enzyme.
- the detached endothelial cells are then dissolved, preferably in a liquid, which is poured onto a culturing dish.
- the object is also achieved by the use initially defined and characterized in that said cell is coated with endothelial cells which are derived from the recipient and are attached to the surface of said cell in such a way that they form a layer of endothelial cells, as well as by the method initially defined and characterized in that said cell is coated with endothelial cells which are derived from the recipient and are attached to the surface of said cell in such a way that they form a layer of endothelial cells.
- a piece of tissue is removed , for example a piece of blood-vessel tissue.
- This piece of tissue may be a piece of vein with a size of about 3 cm.
- a liquid containing an enzyme is applied which causes the detachment of the endothelial cells that exist on the vein-tissue.
- the achieved solution of endothelial cells is poured into a test tube and is centrifugalized so that the enzyme can be removed. Then the endothelial cells are suspended or dissolved in a culturing medium, wherein they have a substantially sphere-like shape.
- the culturing medium is poured onto a culturing dish.
- the endothelial cells will attach to the culturing dish and grow, and be distributed over the surface of the culturing dish.
- the endothelial cells take a substantially flat, extended shape.
- the endothelial cells are detached from the culturing dish in the same way as from the vein tissue and the process is repeated in this way until a sufficient amount of endothelial cells are available.
- the cells to be transplanted are removed from the pancreas of the donor in a manner known per se and are transferred to a container.
- a solution of endothelial cells is poured over the pancreas cells from the donor, wherein the substantially sphere- shaped endothelial cells will attach to the surface of the pancreas cells and be distributed over the same until the whole surface of the pancreas cells is covered with a one-cell-layer of autologous endothelial cells. Also in this case, the endothelial cells will grow and take a substantially flat, extended shape on the surface of the pancreas cells.
- the coated pancreas cells are then transmitted to the patient who is to be treated against diabetes, for example by injection of a solution which comprises these cells coated by endothelial cells.
- a piece of brain tissue is removed from a donor. It may for example be a brain tissue comprising cells, which produce the transmitter substance dopamine.
- the solution with autologous endothelial cells obtained, according to example 1 is then poured over this piece of brain tissue, wherein the endothelial cells will coat the whole surface of the piece of tissue.
- the piece of tissue can then be inserted and be placed in the brain of a patient who suffers from the deficiency of this transmitter substance.
- endothelial cells on blood-vessels from a pig and a human being can be removed from and replaced by endothelial cells which have been cultured from another human being.
- These new endothelial cells present the same biological properties as the original endothelial cells and accept their new underlying tissue without showing any signs on any remarkable activation of the immunological signalling system to potential immunological effector cells. It means in other words that the underlying tissue is regarded as the bodies own because it is covered with autologous endothelial cells.
- a preparation according to the present invention might be produced from all cells from animals and human beings which would be desirable to transplant or transfer to another human being or another animal. It is also possible within the scope of the invention to produce whole organs from a recipient for transplantation to a receiving patient, wherein the organ concerned is coated with autologous endothelial cells of the recipient in accordance with the method which has been described above, before the organ is transplanted into a recipient.
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Materials For Medical Uses (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98941986A EP1005331A1 (en) | 1997-09-01 | 1998-08-31 | Transplants coated with autologous endothelial cells |
AU90132/98A AU9013298A (en) | 1997-09-01 | 1998-08-31 | Transplants coated with autologous endothelial cells |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9703144A SE9703144L (en) | 1997-09-01 | 1997-09-01 | Preparation, method of making a preparation, use of a preparation for treatment and method of treatment |
SE9703144-7 | 1997-09-01 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1999011220A1 true WO1999011220A1 (en) | 1999-03-11 |
WO1999011220A8 WO1999011220A8 (en) | 1999-04-29 |
Family
ID=20408100
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SE1998/001549 WO1999011220A1 (en) | 1997-09-01 | 1998-08-31 | Transplants coated with autologous endothelial cells |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1005331A1 (en) |
AU (1) | AU9013298A (en) |
SE (1) | SE9703144L (en) |
WO (1) | WO1999011220A1 (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994003586A1 (en) * | 1992-08-05 | 1994-02-17 | Scientific Dimensions U.S.A., Inc. | A method for detaching intact cells and reducing implant rejection |
WO1994007432A2 (en) * | 1992-09-29 | 1994-04-14 | Thomas Jefferson University | Porous vascular implants |
WO1996040887A1 (en) * | 1995-06-07 | 1996-12-19 | Children's Medical Center Corporation | Immunoprotective barrier for transplantation of cells |
-
1997
- 1997-09-01 SE SE9703144A patent/SE9703144L/en not_active Application Discontinuation
-
1998
- 1998-08-31 WO PCT/SE1998/001549 patent/WO1999011220A1/en not_active Application Discontinuation
- 1998-08-31 EP EP98941986A patent/EP1005331A1/en not_active Withdrawn
- 1998-08-31 AU AU90132/98A patent/AU9013298A/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994003586A1 (en) * | 1992-08-05 | 1994-02-17 | Scientific Dimensions U.S.A., Inc. | A method for detaching intact cells and reducing implant rejection |
WO1994007432A2 (en) * | 1992-09-29 | 1994-04-14 | Thomas Jefferson University | Porous vascular implants |
WO1996040887A1 (en) * | 1995-06-07 | 1996-12-19 | Children's Medical Center Corporation | Immunoprotective barrier for transplantation of cells |
Also Published As
Publication number | Publication date |
---|---|
SE9703144L (en) | 1999-03-02 |
AU9013298A (en) | 1999-03-22 |
EP1005331A1 (en) | 2000-06-07 |
WO1999011220A8 (en) | 1999-04-29 |
SE9703144D0 (en) | 1997-09-01 |
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