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WO2007102685A1 - Nouvelle méthode de perfusion in vivo induisant une signalisation différentielle chez l'animal - Google Patents

Nouvelle méthode de perfusion in vivo induisant une signalisation différentielle chez l'animal Download PDF

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Publication number
WO2007102685A1
WO2007102685A1 PCT/KR2007/001085 KR2007001085W WO2007102685A1 WO 2007102685 A1 WO2007102685 A1 WO 2007102685A1 KR 2007001085 W KR2007001085 W KR 2007001085W WO 2007102685 A1 WO2007102685 A1 WO 2007102685A1
Authority
WO
WIPO (PCT)
Prior art keywords
novel
growth factor
group
vivo
perfusion method
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/KR2007/001085
Other languages
English (en)
Inventor
Kang-Yeol Choi
Soung-Hoo Jeon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Industry Academic Cooperation Foundation of Yonsei University
Original Assignee
Industry Academic Cooperation Foundation of Yonsei University
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 Industry Academic Cooperation Foundation of Yonsei University filed Critical Industry Academic Cooperation Foundation of Yonsei University
Publication of WO2007102685A1 publication Critical patent/WO2007102685A1/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
    • 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
    • A61M60/00—Blood pumps; Devices for mechanical circulatory actuation; Balloon pumps for circulatory assistance
    • A61M60/40—Details relating to driving
    • A61M60/403—Details relating to driving for non-positive displacement blood pumps
    • A61M60/419—Details relating to driving for non-positive displacement blood pumps the force acting on the blood contacting member being permanent magnetic, e.g. from a rotating magnetic coupling between driving and driven magnets
    • 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
    • A61M25/00—Catheters; Hollow probes
    • 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
    • A61M29/00—Dilators with or without means for introducing media, e.g. remedies
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N11/00—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties
    • 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
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/04—General characteristics of the apparatus implanted
    • 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
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/82—Internal energy supply devices

Definitions

  • the present invention relates to a perfusion method for inducing modifications
  • the present invention relates to a method for facilitating various researches
  • cytokines or various drugs into organs each of which is present in at least a pair in one
  • this method may be used to easily obtain a large amount of protein extracts of
  • the method may be effectively used in the field of a variety of applications, particularly the research and development
  • administered factors may have affects on a target tissue and other tissues, and they also
  • proteomics technologies such as protein chips, two-dimensional
  • the present invention is designed to solve the problems of the prior
  • transductions cell growth factor, cell inhibitory factors, compounds or the like
  • the in vivo perfusion method makes possible to obtain a control sample having the same genetic traits and conditions and obtain a large amount of a desired protein.
  • the present invention provides a novel in vivo perfusion method including a) incising an abdominal region of an animal to
  • liver tissue an artery and a vein, the liver tissue being composed of multiple lobes to be perfused; b) inserting a blood vessel catheter into the vein and
  • the suitable organ in the present invention includes, but is not limited to, an
  • organ selected from the group consisting of liver composed of multiple lobes, kidney
  • the catheter of the present invention is preferably fixed with suture (for
  • the solution used as the control group preferably includes one selected
  • salines for example, Ringer's
  • the experimental group compound of the present invention preferably phosphate-buffered saline (PBS)
  • the cell growth-associated signaling molecules of the present invention are cell growth-associated signaling molecules of the present invention.
  • Wntl preferably includes Wntl, Wnt2, Wnt3a, Wnt5a, Wnt5b, Wnt7a, Wntl l, epidermal
  • EGF epidermal growth factor
  • HGF hepatocyte growth factor
  • PDGF fibroblast growth factor
  • FGF fibroblast growth factor
  • TGF transforming growth factor
  • IGF insulin-like growth factor
  • the compound of the present invention is more preferably selected from the
  • growth factors lithium chloride, calcium chloride, tautomycetin and
  • VPA valproic acid
  • the present invention provides a method for inducing
  • differential signaling in organs, particularly a liver which is present in a pair in one animal.
  • cytokines compounds or the like-specific or -dependent manner.
  • the organs that are present in a pair are present in a pair
  • liver tissue or a kidney tissue are suitably used as the target tissue, and
  • the cell growth-associated signaling molecules are preferably Wnt such as Wntl, Wnt2,
  • Wnt3a, Wnt5a, Wnt5b, Wnt7a, and Wntl l epidermal growth factor (EGF), hepatocyte
  • HGF growth factor
  • PDGF platelet-derived growth factor
  • FGF transforming growth factor
  • IGF insulin-like growth factor
  • saline is injected into a vein of a target liver tissue
  • the present invention may be useful to observe reaction to a signal stimulus in an in vivo level, the signal stimulus being able to appear for a very short period of 1 to 10 minutes,
  • FIG. 1 is a schematic view showing a novel perfusion method including steps of
  • control group administering various ligands or chemical compounds including growth
  • FIG. 2 is a diagram showing experimental tools used in the perfusion method of
  • FIG. 3 a ((D) is a diagram showing a liver, a hepatic vein and an artery of a
  • mice which is anesthetized with ethyl ether and incised at an abdominal region for
  • FIG. 3b ( ⁇ ) is a diagram showing that a
  • suture is installed under a hepatic vein that a blood vessel catheter will be inserted for its
  • FIG. 3c ((3)) is a diagram showing that the blood vessel catheter is inserted
  • ( ⁇ ) is a diagram showing that the blood vessel catheter inserted into the hepatic vein is
  • liver lobes blood in the liver is washed by circulating about 50 ml of previously prepared saline for 10 minutes using an air-compressor pump, and one of three liver lobes is selected and a suture is installed in a bottom of the selected liver lobe
  • FIG. 3e ((B)) is a diagram showing
  • FIG. 3f ( ⁇ ) is a diagram showing that, after the separated control liver tissue is taken
  • the perfusion tube is transferred to a vial containing 50 ml of an experimental-group
  • FIG. 3g ((D) is a diagram showing that, after the experimental-group
  • FIG. 4 is a diagram showing that the frozen mouse liver tissues of the control
  • each of the resultant tissue extracts is centrifuged
  • fraction is subject to 10% SDS-PAGE to separate a target protein, and phosphorylated
  • Raf-1, MEK, ERK and ⁇ -tubulin which are all associated with activation of certain
  • proteins in a Ras-ERK signaling system are subject to western blotting using specific
  • FIG. 5 is a diagram showing that the perfused mouse liver tissues of the control
  • tissue extracts are pulverized to obtain tissue extracts
  • the resultant tissue extracts are centrifuged (fractionated) to obtain a cytoplasmic protein fraction
  • the cytoplasmic protein fraction is subject to 10% SDS-PAGE to separate a target protein, and phosphorylated
  • ERK phosphorylated Akt and GSK3b
  • ⁇ -tubulin are subject to western blotting
  • the phosphorylated ERK and the phosphorylated Akt being associated with activation of certain proteins in a Ras-ERK signaling system and an Akt
  • FIG. 6 is a diagram showing that the perfused mouse liver tissues of the control
  • tissue extracts each of the resultant tissue extracts are divided into
  • WL crude tissue cell
  • PM membrane protein fraction
  • Cy cytoplasm fraction
  • nucleoprotein fraction (Nu) and a nucleoprotein fraction (Nu), and each fraction is western-blotted using antibodies
  • FIG. 7 is a diagram showing that a mouse NIH3T3 fibroblast cell line is treated
  • mice and rats used in this experiment may be variously several weeks old, and
  • mice used in the present invention were male and 12 weeks old from the ICR birth, and 50 ml of epidermal growth factor (20 ng/ml EGF, 100ng/ml IGF-I or 20 niM LiCl) was administered to the mice.
  • epidermal growth factor (20 ng/ml EGF, 100ng/ml IGF-I or 20 niM LiCl) was administered to the mice.
  • mice The surgical tools had a suitable size for small mice, and their kinds are shown
  • Anesthesia of a mouse was carried out by dipping a gauze in ethyl ether and
  • anesthesia time of the mouse was 3 to 5 minutes, and its heart beat should be
  • a surgical suture was installed in a lower part of the exposed hepatic vein using
  • liver tissue was changed from dark brown to light brown, indicating that the liver is normally perfused
  • FIG. 3c ((H)) and FIG. 3d ( ⁇ )).
  • a suture was installed in a bottom of a right lobe of
  • liver while the liver was perfused with saline, and then a blood vessel passed through the right liver lobe was tied up and extracted as a control group, which will be
  • EGF EGF, 20ng/ml
  • the perfusion may be failed since a solution may not enter the space. If the injection of
  • the cell growth factor is completed, the other liver tissues were extracted and
  • the extract of the liver tissue was centrifuged at 4 ° C at a rotary speed of 800 x
  • sucrose centrifuged at 4 ° C at a rotary speed of 45,000 rpm for 45 minutes, and then
  • liver tissue stored in liquid nitrogen was ground into powder using a pestle
  • IGF 100 ng/ml, Example 2
  • 20 mM LiCl 20 mM LiCl
  • Example 1 administered compound, respectively, instead of the EGF (20 ng/ml) used in Example 1.
  • Example 4 was repeated in the same manner as in Example 1 to obtain a cell
  • the resultant cell extract was electrophoresed, and the electrophoresed gel was transferred into a protein transfer membrane and western-blotted using a specific antibody to the target proteins to observe the increased target proteins.
  • a level of the target proteins p-Raf-1, p-MEK and p-ERK and
  • EGF epidermal growth factor
  • Example 5 was repeated in the same manner as in Example 1 to obtain a cell
  • target proteins p-Raf-1, p-MEK and p-ERK and
  • Example 6 was repeated in the same manner as in Example 1 to obtain a cell
  • nucleus marker protein Histone 1 The cell extract or the protein samples were
  • LiCl which is a regulatory compound in a Wnt/ ⁇ -catenin signaling
  • Mouse fibroblast NIH3T3 cell was treated with LiCl (0, 5, 20, 50 mM) for 15
  • the present invention may solve the problems caused by

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Hematology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Mechanical Engineering (AREA)
  • Cardiology (AREA)
  • Analytical Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Pathology (AREA)
  • Biophysics (AREA)
  • Pulmonology (AREA)
  • Immunology (AREA)
  • General Physics & Mathematics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention porte sur une nouvelle méthode de perfusion in vivo permettant d'obtenir une importante quantité de protéines ainsi que le plus idéal des échantillons de protéines de référence, les protéines spécifiquement modifiées pour la signalisation de cellules sont transformées dans la forme la plus similaire pour être présentes dans des conditions in vivo. L'invention porte plus particulièrement sur une méthode facilitant les recherches sur des maladies dues à une signalisation anormale des cellules, ou sur le criblage de différents médicaments et de ligands in vivo sous une forme similaire à celle des conditions in vivo. L'invention porte également sur une méthode innovante de résolution de problèmes tels que la faible quantité d'échantillons obtenus et de références lors de leur production, sur des études sur les modifications directes de tissus ou de cellules, produites par différents composés (par exemple les facteurs de croissance cellulaire ou certains produits médicaux) qu'on administre pour élucider le mécanisme de signalisation d'une cellule et un phénomène physiologique.
PCT/KR2007/001085 2006-03-06 2007-03-06 Nouvelle méthode de perfusion in vivo induisant une signalisation différentielle chez l'animal Ceased WO2007102685A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2006-0020986 2006-03-06
KR1020060020986A KR100797908B1 (ko) 2006-03-06 2006-03-06 동일개체 내에서 차별적으로 신호전달을 유도할 수 있는새로운 생체 내 관류 법

Publications (1)

Publication Number Publication Date
WO2007102685A1 true WO2007102685A1 (fr) 2007-09-13

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WO (1) WO2007102685A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101068449B1 (ko) * 2007-10-26 2011-09-28 강원대학교산학협력단 직접 혈액관류 시스템을 이용한 이소성 신장 관류 방법

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4869253A (en) * 1986-08-18 1989-09-26 Physio-Control Corporation Method and apparatus for indicating perfusion and oxygen saturation trends in oximetry
WO2004034898A2 (fr) * 2002-10-15 2004-04-29 Philips Intellectual Property & Standards Gmbh Procede de presentation d'informations concernant des variations dans une perfusion

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4869253A (en) * 1986-08-18 1989-09-26 Physio-Control Corporation Method and apparatus for indicating perfusion and oxygen saturation trends in oximetry
WO2004034898A2 (fr) * 2002-10-15 2004-04-29 Philips Intellectual Property & Standards Gmbh Procede de presentation d'informations concernant des variations dans une perfusion

Also Published As

Publication number Publication date
KR20070091458A (ko) 2007-09-11
KR100797908B1 (ko) 2008-01-24

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