EP1307543A2 - Autologe bindegewebe, verfahren zu ihrer herstellung und ihre verwendung - Google Patents
Autologe bindegewebe, verfahren zu ihrer herstellung und ihre verwendungInfo
- Publication number
- EP1307543A2 EP1307543A2 EP01964866A EP01964866A EP1307543A2 EP 1307543 A2 EP1307543 A2 EP 1307543A2 EP 01964866 A EP01964866 A EP 01964866A EP 01964866 A EP01964866 A EP 01964866A EP 1307543 A2 EP1307543 A2 EP 1307543A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- connective tissue
- cells
- autologous
- stimulation
- takes place
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
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
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0655—Chondrocytes; Cartilage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- 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
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/10—Growth factors
- C12N2501/155—Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
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- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/30—Hormones
- C12N2501/38—Hormones with nuclear receptors
- C12N2501/39—Steroid hormones
Definitions
- the invention relates to autologous connective tissue, processes for their production, their stabilization and their use as grafts.
- the tissues are produced by isolating suitable connective tissue cells, such as cartilage, perichondrium and / or periosteal cells and the corresponding precursor cells, multiplying them in vitro (tissue engineering), embedding them in a three-dimensional matrix, implanting them and stimulating them with corticosteroids.
- suitable connective tissue cells such as cartilage, perichondrium and / or periosteal cells and the corresponding precursor cells
- tissue engineering tissue engineering
- the tissues according to the invention are suitable for use as tissue engineering transplants, in particular as cartilage and bone tissues.
- Autologous tissue replacement can be produced in sufficient quantity using the tissue engineering method (patents: DE 4306661, DE 4431598, US 5891455, US 5932459, DE 4431598) - the problems of larger tissue defects would be compensated for.
- the tissue is used for transplantation into corresponding defects.
- the invention has for its object to improve the production of autologous vital tissue replacement materials.
- the object was achieved in that suitable connective tissue cells, such as cartilage and / or perichondrium and / or periosteal cells and the corresponding precursor cells, were isolated, expanded in vitro (tissue engineering), embedded in a three-dimensional matrix and stimulated by corticosteroids.
- suitable connective tissue cells such as cartilage and / or perichondrium and / or periosteal cells and the corresponding precursor cells.
- tissue engineering tissue engineering
- the essence of the invention is the temporary immunosuppression of the recipient of tissue engineering grafts.
- connective tissue cells for example stimulated - ie stimulated in growth, differentiation or maturation - chondrocytes are isolated, then increased and brought into the desired transplant form with biocompatible materials.
- the graft bed is treated once with a corticoid, followed by systemic administration of corticosteroids for about three weeks.
- Fibrin glue, alginate, hyaluronic acid, agarose and others are used as biocompatible materials, the combinations fibrin glue and hyaluronic acid as well as agarose and fibrin glue according to the invention.
- corticosteroids also mature and differentiate the graft in vivo (in vivo tissue engineering).
- An additional solution to protect against resorption and to stabilize grafts is the encapsulation of the autologous grafts.
- the encapsulation of heterologous grafts by means of cultivated cartilage tissue has already been described by Vacanti (US 5741685); however, this invention does not solve the problem of the stability of the grown cartilage itself.
- the procedure according to the invention allows the production of autologous cartilage and bone tissue, in particular plastic reconstructions and replacement for traumatic lesions (e.g. ear, nose, trachea, esophagus).
- the combination consists of known elements (tissue engineering grafts, connective tissue cells and their proliferation) and new ones (corticosteroids as a means of reducing rejection or infiltrative, inflammatory reactions in autologous grafts and corticosteroids as a growth and differentiation stimulus), which mutually influence and result in a new benefit in use (synergistic effect) and the desired success, which lies in the fact that now, with good tolerance for the recipient, a way to reduce non-specific and specific rejection reactions, which have limited the survival of the grafts, is shown.
- Another combination feature is that the biocompatible materials are used in new combinations - fibrin glue and hyaluronic acid as well as agarose and fibrin glue.
- This application claims autologous connective tissue that can be produced by isolating suitable connective tissue cells, increasing them in vitro (tissue engineering), embedding them in a three-dimensional matrix, then implanting them and stimulating them with corticosteroids.
- the corticosteroid-stimulated connective tissue cells are isolated in the form of cartilage and / or perichondrium and / or periosteal cells and / or their corresponding progenitor cells.
- Autologous connective tissue of the type mentioned can be produced, for example, by isolating stimulated chondrocytes, then increasing them and using them biocompatible materials are brought into the desired graft shape, after the implantation the graft bed is treated once with a corticoid and then a systemic application of corticosteroids takes several weeks.
- the corticosteroids also mature and differentiate the graft in vivo (in vivo tissue engineering).
- corticosteroids are temporarily administered in anti-inflammatory dosage for about three weeks.
- the corticosteroids are administered e.g.
- the local administration of corticosteroids in anti-inflammatory doses into the transplant bed for one time or for about three weeks is carried out temporarily.
- the production of bone tissue from corticosteroid-stimulated chondrocytes, perichondrial cells, periosteal cells and the corresponding precursor cells is based, for example, on that the stimulation of the corresponding connective tissue cells takes place in vitro before the implantation; for this purpose, the corticoids are added to the cell growth medium in appropriate doses - after the implantation takes place in vivo; the corticoids are applied to the transplant recipient; the application is as a long-term depot intramuscularly, daily intramuscularly, daily intravenously or daily orally.
- the production of grafts is carried out using a three-dimensional shape made of a bioabsorbable material or in the form of a suspension for insertion (e.g. injection) into corresponding defects.
- the encapsulation of autologous tissue engineering grafts for the purpose of biomechanical protection and mechanical immunological shielding / delimitation and matrix accumulation involves, with regard to the delimitation of grafts, hydrogels, hyaluronic acid, agarose, alginate, fibrin glue or the like Capsule / delimitation of the graft from one or more Zeil layers
- Connective tissue cells e.g. fibroblasts
- progenitor cells e.g. fibroblasts
- it is a membrane made of collagen, chitosan, proteoglycans or hyaluronic acid (or
- Anti-inflammatory and anti-angiogenic factors can be incorporated into both the graft and the matrix.
- BMP-7 (BMP - bone morphogenetic protein), in particular, is brought into the graft or into the capsule as an anti-inflammatory factor.
- cyclosporins or inhibitors are also more inflammatory
- cartilage cells are isolated by means of an enzyme mix of collagenases and hyaluronidase. The subsequent multiplication of the cells takes place in cell culture bottles.
- the medium used is, for example, RPMI (commercially available cell culture medium) which, in addition to other additives, contains the serum of the animal species or of humans for which the graft to be produced is produced.
- biocompatible materials such as fibrin glue, alginate, hyaluronic acid [Lindenhayn K, Spitzer R, Heilmann HH, Perka C, Pommering K, Mennicke K, Sittinger M (1999) Retention of hyaluronic acid in alginate beads : aspects for in vitro cartilage engineering J Biomed Mat. Res.
- Systemic administration is based on the biorhythm of the endogenous cortisol. In order to prevent adrenal insufficiency, the dose level is reduced with the days.
- Example 1 as example 0, but with cartilage and perichondrium cells instead of chondrocytes as well as fibrin glue and hyaluronic acid as a biocompatible material.
- Example 2 as example 0, but with perichondrium and / or periosteal cells as well as fibrin glue and agarose as a biocompatible material.
- Example 3 as example 0, but with cartilage, perichondrium cells and / or their corresponding cartilage, perichondrium cells and / or their corresponding cartilage, perichondrium cells and / or their corresponding cartilage, perichondrium cells and / or their corresponding cartilage, perichondrium cells and / or their corresponding cartilage, perichondrium cells and / or their corresponding cartilage, perichondrium cells and / or their corresponding
- Progenitor cells as well as fibrin glue and agarose as a biocompatible material.
- Example 4 as example 0, but with fibrocytes and / or fibroblasts.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Rheumatology (AREA)
- Zoology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cell Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Prostheses (AREA)
- Materials For Medical Uses (AREA)
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10038700 | 2000-07-31 | ||
DE10038700A DE10038700B4 (de) | 2000-07-31 | 2000-07-31 | Autologe Bindegewebe, Verfahren zu ihrer Herstellung und ihre Verwendung |
PCT/DE2001/002899 WO2002010351A2 (de) | 2000-07-31 | 2001-07-30 | Autologe bindegewebe, verfahren zu ihrer herstellung und ihre verwendung |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1307543A2 true EP1307543A2 (de) | 2003-05-07 |
Family
ID=7651736
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP01964866A Withdrawn EP1307543A2 (de) | 2000-07-31 | 2001-07-30 | Autologe bindegewebe, verfahren zu ihrer herstellung und ihre verwendung |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP1307543A2 (de) |
DE (1) | DE10038700B4 (de) |
WO (1) | WO2002010351A2 (de) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10253066A1 (de) * | 2002-11-07 | 2004-05-27 | Co.Don Aktiengesellschaft | Gewebeersatzstruktur, Verfahren zur Modifikation einer Gewebeläsion und Verwendung von vorgeformtem dreidimensionalem Gewebe als Lieferant von Botenstoffen und/oder Strukturbausteinen |
US7744869B2 (en) | 2003-08-20 | 2010-06-29 | Ebi, Llc | Methods of treatment using electromagnetic field stimulated mesenchymal stem cells |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999009149A1 (en) * | 1997-08-01 | 1999-02-25 | Massachusetts Institute Of Technology | Three-dimensional polymer matrices |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4431598C2 (de) * | 1993-03-03 | 1997-03-20 | Michael Sittinger | Verfahren zum Herstellen eines Implantates aus Zellkulturen |
WO1997015655A2 (de) * | 1995-10-20 | 1997-05-01 | Michael Sittinger | Neue künstliche gewebe, verfahren zu ihrer herstellung und ihre verwendung |
DE19835368C1 (de) * | 1998-08-05 | 2000-02-10 | Juergen Steinmeyer | Verfahren zur Herstellung einer Knorpelzellsuspension |
FR2798671A1 (fr) * | 1999-09-16 | 2001-03-23 | Univ Paris Curie | Compositions de chondrocytes, preparation et utilisations |
-
2000
- 2000-07-31 DE DE10038700A patent/DE10038700B4/de not_active Expired - Fee Related
-
2001
- 2001-07-30 WO PCT/DE2001/002899 patent/WO2002010351A2/de active Application Filing
- 2001-07-30 EP EP01964866A patent/EP1307543A2/de not_active Withdrawn
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999009149A1 (en) * | 1997-08-01 | 1999-02-25 | Massachusetts Institute Of Technology | Three-dimensional polymer matrices |
Non-Patent Citations (7)
Also Published As
Publication number | Publication date |
---|---|
DE10038700B4 (de) | 2006-09-07 |
WO2002010351A3 (de) | 2002-09-12 |
DE10038700A1 (de) | 2002-02-21 |
WO2002010351A2 (de) | 2002-02-07 |
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Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR |
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Owner name: SCHMITT-WALBURG GBR |
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