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WO2003040298A2 - Procede d'alimentation en oxygene de cultures de micro-organismes, de cultures de cellules organiques animales ou humaines et de cultures tissulaires ou d'organoides en cours de culture ou d'organes en cours de culture - Google Patents

Procede d'alimentation en oxygene de cultures de micro-organismes, de cultures de cellules organiques animales ou humaines et de cultures tissulaires ou d'organoides en cours de culture ou d'organes en cours de culture Download PDF

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Publication number
WO2003040298A2
WO2003040298A2 PCT/EP2002/008370 EP0208370W WO03040298A2 WO 2003040298 A2 WO2003040298 A2 WO 2003040298A2 EP 0208370 W EP0208370 W EP 0208370W WO 03040298 A2 WO03040298 A2 WO 03040298A2
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WO
WIPO (PCT)
Prior art keywords
substances
oxygen
use according
substance
culture
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.)
Ceased
Application number
PCT/EP2002/008370
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German (de)
English (en)
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WO2003040298A3 (fr
WO2003040298B1 (fr
Inventor
Wolfgang Fege
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Individual
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Individual
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Publication date
Application filed by Individual filed Critical Individual
Priority to EP02799039A priority Critical patent/EP1451298A2/fr
Priority to AU2002363454A priority patent/AU2002363454A1/en
Publication of WO2003040298A2 publication Critical patent/WO2003040298A2/fr
Publication of WO2003040298A3 publication Critical patent/WO2003040298A3/fr
Publication of WO2003040298B1 publication Critical patent/WO2003040298B1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61K35/14—Blood; Artificial blood

Definitions

  • the invention relates to the use of substances which reversibly bind oxygen for the transport, transmission and storage of oxygen in the oxygen supply of cultures of microorganisms and / or of animal and / or human body cells and / or of tissue cultures.
  • hemoglobins It is known that hemoglobins, myoglobins, hemoeyanins and perfluorocarbons bind oxygen reversibly, and thus also store and are used for oxygen transport and / or storage in multicellular organisms.
  • yoglobine be because of their high oxygen binding affinity primarily to Sauersto used storage, because myoglobin release oxygen only at very low Sauersto artial horr to the environment again * Myoglobins form the red dye of the skeletal muscles and have their highest concentration in the heart muscle of diving SeesSugern. Hemo lobins are mainly used for
  • Oxygen transport used since their oxygen binding curve runs in such a way, with the usual oxygen partial pressure of the arterial blood ate the hemoglobin is oxygen saturated and with the oxygen partial pressure of the blood capillaries the oxygen binding capacity is very low, whereby the transported oxygen can be released almost completely.
  • This oxygen binding curve changes with a change in pH and / or temperature and is different for different hemoglobins
  • Hemoglobin ⁇ is transported in blood cells in all vertebrates. However, they occur dissolved in the blood plasma in slipper animals, echinoderms / round and ringworms and in some crayfish. This proves that hemoglobins are also effective oxygen transporters if they are not encapsulated in blood cells.
  • Hemoeyanins also serve to transport oxygen in soft and arthropods.
  • Pe luorcarbone are synthetic oxygen binders and were experimentally added to the blood plasma as a partial hemoglobin substitute.
  • Monomeric free hemoglobin is not used because it leads to narrowing of the blood vessels and is excreted too quickly via the kidneys. However, these undesirable properties are of no importance when used in the usual tissue, cell or microorganism cultures, so that free monomeric hemoglobin can be used here. It is also known that even very small amounts of free polymerized swine hemoglobin Significantly increase oxygen diffusion.
  • Oxygen is likely to be passed on via free hemoglobins in tissue, similar to the electrical current in an electrical conductor, and not just transported. This comparison may be permissible because the polar oxygen is used to transport electrons to the cellular power plants, the mi ochondria. Here, the oxygen binds temporarily to electrical conductors via some of the electrons to be transported, namely the iron atoms in heme or the copper atoms in hemocyanin.
  • the oxygen diffusion rate decreases very quickly over short distances, even a slight improvement in the diffusion rate can result in a significant improvement in the oxygen supply to a tissue.
  • a sole transmission of oxygen in tissue, rope or microorganism cultures is probably sufficient to supply oxygen, at least over distances of a few millimeters.
  • the possible route length also depends on the oxygen consumption and the number or density of cells and microorganisms.
  • the broad conduction of oxygen can take place continuously or discontinuously via reversible oxygen-binding substances.
  • the molecules of these substances can thus touch or not, so they can be distributed continuously or discontinuously in a culture. Both forms of distribution can change locally and / or line by line or occur simultaneously. The form of distribution can also change with the type of substance.
  • oxygen with reversible oxygen-binding substances can also be stored in the tissue. All of these phenomena can be used advantageously in extrac ⁇ rporal tissue cultivation, the extracorporeal cultivation of cells or the cultivation of microorganisms for improving the oxygen supply or at least for a part of the oxygen supply.
  • one or more reversibly oxygen-binding substances or a substance mixture or several substance mixtures can be loaded with oxygen at one or more external oxygen sources and then supplied to the cultures described above. These substances or mixtures can be added to the cultures, stored in them or passed through the cultures. This can be done in an open, semi-open or closed cycle, but also without a cycle of these substances or mixtures. Any local and temporal combination of all of the above-mentioned methods is also possible.
  • One or more oxygen sources can also be on or in such cultures. In its simplest form, such a source would be the oxygen in the surrounding or supplied air, but also in other surrounding or supplied gas mixtures or supplied or introduced oxygen itself. The arrangement and / or selection of oxygen sources is also. can be combined as required.
  • the reversible oxygen-binding substances would not necessarily have to be moved here if the oxygen supply to the culture via a transfer with the aid of these substances is sufficient.
  • any combination of oxygen transport and oxygen transmission and / or oxygen storage is also possible.
  • different reversible oxygen-binding substances can be or are distributed homogeneously and / or inhomogeneously in any type and / or combination, which not only bind and / or transmit and / or store oxygen differently, but also on the basis of their different chemical and / or physical properties have different affinities for parts in culture in general but also different binding forces in particular.
  • This can e.g. by cells or microorganisms producing such substances.
  • Reversible oxygen-storing substances can be added individually or in any mixtures of the nutrient liquid or parts of the sewing liquid. These substances can be supplied with oxygen via an oxygenator and then released again in the vicinity of the tissue to be cultivated, the cell or microorganism culture and / or via a passage and / or introduction directly into the tissue, cell or microorganism culture. Also or in combination with this, such reversibly oxygen-binding substances can be arranged homogeneously and / or inhomogeneously individually or in any mixture in the tissue to be cultivated, in the cell or microorganism culture.
  • oxygen would not only be transported, but would also be passed on, and tissue monitoring or a culture of cells or microorganisms can be influenced differently in different areas by an innomogeneous arrangement of the reversible oxygen-binding substances.
  • oxygen can also be stored in these substances.
  • a tissue, tissue mixture, organoid or organ in cultivation or cultivated can be supplied with sufficient oxygen until blood vessels have possibly formed with the addition of growth factors.
  • newly formed blood vessels seek to connect to existing blood vessels through which blood flows, it makes sense to introduce nutrient fluid into this tissue via channels.
  • channels can be perforated so that capillaries can connect to the perforations.
  • the channels can also branch out. This can be done similar to a capillary network. Perforation of the channels is particularly advantageous if the channels are passed through and thus do not end in the tissue.
  • An accumulation of individual or different reversible oxygen-binding substances on fibers or embedding in hollow fibers can be helpful in transporting the oxygen specifically into certain tissue areas.
  • the direction of capillary growth which takes place in the direction of the oxygen partial pressure, can also be influenced in this way by inhomogeneous distribution of the reversibly aerosol-binding substances.
  • Capillaries could e.g. grow along or in the direction of fibers coated with these substances or grow in hollow fibers filled with these substances.
  • Capillary growth can also be supported by the attachment of growth actuators to and / or in fibers and / or hollow asers.
  • tissues that usually have little or no blood vessels such as cartilage tissue
  • tissues that usually have little or no blood vessels such as cartilage tissue
  • reversibly oxygen-binding substances can be added, injected, introduced by diffusion, for example with the nutrient flow, mixed in at the beginning of the breeding or distributed inhomogeneously at the beginning * All of these can be combined in any place and / or time.
  • the different molecular size such as 3.B. of mono erer hemoglobin and polymeric hemoglobin, but also different polarity can be used "in order to achieve a different penetration and a different penetration of the cultures or tissues during perfusion, similar to a chromatography.
  • the binding capacity in the tissue is dependent on the polarity and molecular size of these substances, so that some of them have the same perfusion rate and the same perfusion pressure
  • Substances do not move, or move only a little, and thus primarily transmit the oxygen, while other fast-moving substances primarily transport the oxygen. Can also be artificially encapsulated
  • reversibly oxygen-binding substances can be stored in a stranded and / or branched manner and / or chemically in one another
  • Tissue cultivation e.g., the patient, which cultured
  • Intact red blood cells can also be added to the tissue, for example by means of injection or mixing, for example for use as an oxygen store.
  • Genetically modified cells or microorganisms can also be added to cell or microorganism cultures, in particular, which themselves reversibly produce oxygen-binding substances, whereby they can discharge and / or accumulate these substances.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Zoology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne l'utilisation de substances fixant l'oxygène de manière réversible, pour transporter, transférer et stocker de l'oxygène pour assurer l'alimentation en oxygène lors de la culture d'organes, de structures de type organe, de cultures tissulaires, de cultures de cellules humaines ou animales ou de cultures de micro-organismes. A cet effet, plusieurs propriétés possibles de telles substances peuvent être utilisées. D'une part la propriété de fixer l'oxygène à pression partielle élevée et de le rejeter dans l'environnement à pression partielle plus basse, de sorte à permettre un transport d'oxygène. D'autre part, la capacité de stocker de l'oxygène et de ne le rejeter qu'à des pressions partielles très basses. Il est également possible d'exploiter la capacité de certaines de ces substances, à bien transférer de l'oxygène de manière différenciée. L'adjonction de substances fixant l'oxygène de manière réversible à des cultures d'organes, d'organoïdes, de tissus, de cellules ou de micro-organismes permet de parvenir à une alimentation suffisante en oxygène, même dans les zones où il ne serait pas possible, sans ces substances, dans des conditions sinon identiques, d'assurer une alimentation suffisante en oxygène pour la survie ou un bon fonctionnement de cellules ou de micro-organismes requérant de l'oxygène.
PCT/EP2002/008370 2001-07-30 2002-07-26 Procede d'alimentation en oxygene de cultures de micro-organismes, de cultures de cellules organiques animales ou humaines et de cultures tissulaires ou d'organoides en cours de culture ou d'organes en cours de culture Ceased WO2003040298A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP02799039A EP1451298A2 (fr) 2001-07-30 2002-07-26 Croissance de cellules et tissus en utilisant des substances qui lient de facon reversible l'oxygene
AU2002363454A AU2002363454A1 (en) 2001-07-30 2002-07-26 Cell and tissue growth using substances that reversibly bind oxygen

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10136912.3 2001-07-30
DE10136912A DE10136912A1 (de) 2001-07-30 2001-07-30 Verfahren zur Sauerstoffversorgung von Mikroorganismenkulturen, Kulturen von tierischen oder menschlichen Körperzellen und von Gewebekulturen, Organoiden, Organen

Publications (3)

Publication Number Publication Date
WO2003040298A2 true WO2003040298A2 (fr) 2003-05-15
WO2003040298A3 WO2003040298A3 (fr) 2003-10-16
WO2003040298B1 WO2003040298B1 (fr) 2003-12-04

Family

ID=7693473

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2002/008370 Ceased WO2003040298A2 (fr) 2001-07-30 2002-07-26 Procede d'alimentation en oxygene de cultures de micro-organismes, de cultures de cellules organiques animales ou humaines et de cultures tissulaires ou d'organoides en cours de culture ou d'organes en cours de culture

Country Status (4)

Country Link
EP (1) EP1451298A2 (fr)
AU (1) AU2002363454A1 (fr)
DE (1) DE10136912A1 (fr)
WO (1) WO2003040298A2 (fr)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU653922B2 (en) * 1989-10-30 1994-10-20 California Institute Of Technology Enhancement of cell growth by expression of a cloned hemoglobin gene
AU6766994A (en) * 1994-04-01 1995-10-23 Unisyn Technologies, Inc. Culture media additives for hollow fiber bioreactors

Also Published As

Publication number Publication date
WO2003040298A3 (fr) 2003-10-16
DE10136912A1 (de) 2003-02-20
EP1451298A2 (fr) 2004-09-01
WO2003040298B1 (fr) 2003-12-04
AU2002363454A1 (en) 2003-05-19

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