WO2020020089A1 - Applications d'un anticorps spécifique, instrument médical implantable et procédé de préparation associé - Google Patents

Applications d'un anticorps spécifique, instrument médical implantable et procédé de préparation associé Download PDF

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Publication number
WO2020020089A1
WO2020020089A1 PCT/CN2019/096999 CN2019096999W WO2020020089A1 WO 2020020089 A1 WO2020020089 A1 WO 2020020089A1 CN 2019096999 W CN2019096999 W CN 2019096999W WO 2020020089 A1 WO2020020089 A1 WO 2020020089A1
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Prior art keywords
medical device
specific antibody
atp
antibody
implanted medical
Prior art date
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PCT/CN2019/096999
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English (en)
Chinese (zh)
Inventor
王玄
陈陆
李俊菲
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上海微创医疗器械（集团）有限公司
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Publication of WO2020020089A1 publication Critical patent/WO2020020089A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/02—Methods for coating medical devices

Definitions

  • the invention belongs to the technical field of biomedicine, and particularly relates to the use of a specific antibody, an implanted medical device and a preparation method thereof.
  • Atherosclerotic diseases can cause damage to the vascular endothelium, which can cause diseases such as thrombosis and inflammation, and cause myocardial infarction. If the damaged tissue cannot be repaired during treatment, it will lead to intimal hyperplasia and restenosis of the blood vessels, thus endangering the patient's life.
  • Hematopoietic stem cells are adult stem cells in the blood system with long-term self-renewal capabilities and the potential to differentiate into various types of mature blood cells.
  • the surface of medical devices implanted in the blood system is loaded with substances that can capture hematopoietic stem cells, and induce hematopoietic stem cells to differentiate into the required types of cells in situ as required, which can improve the device's treatment and tissue repair effects.
  • the left atrial appendage is an auricular sac protruding from the left atrium and belongs to the left atrium. It is the main component of the left atrium.
  • Left atrial appendage occlusion was developed by Boston Scientific and approved for marketing in Europe in 2006. On December 31, 2013, it was officially approved by the China Food and Drug Administration for listing and officially launched in China in March 2014.
  • the left atrial appendage the root site of thrombosis in patients with AF, can be used to reduce the risk of stroke in patients with AF.
  • the surface of the occluder is covered with an expandable polytetrafluoroethylene film, which is similar to general implanted medical devices. It also needs to be loaded with drugs that repair damaged tissues to prevent the adverse consequences of surgery.
  • Hoechst 33342 is a fluorescent dye that can stain the DNA of living cells. Its excitation light is 350 nm and the emitted light is divided into two bands. When analyzing the emitted light of Hoechst33342 in two different bands in whole bone marrow cells at the same time, there is a small group of cells that are significantly different from the main group in the double negative region. After analysis, the surface molecular markers of this group of cells are consistent with hematopoietic stem cells. This phenomenon is due to the presence of proteins on the membrane of hematopoietic stem cells that pump Hoechst 33342 dye out.
  • medical devices that promote endothelial repair are generally achieved by loading small molecular compounds or compositions on the surface of medical devices, which are all based on the mechanism of promoting cell growth.
  • this method is generally poor in specificity. While promoting endothelial growth, it also promotes the growth of other cells, including smooth muscle and fibroblasts, resulting in adverse consequences such as restenosis of blood vessels and thrombosis.
  • the side effects of the drugs in this way are large, which can bring other adverse effects.
  • the invention provides the use of a specific antibody, an implanted medical device and a preparation method thereof, which are used to provide a new way to promote endothelial repair.
  • the invention provides a use of a specific antibody, the specific antibody is a specific antibody of an ATP-binding box protein, and the use is in the preparation of a medicament for promoting endothelial repair.
  • a specific antibody is a specific antibody of an ATP-binding box protein
  • the use is in the preparation of a medicament for promoting endothelial repair.
  • the ATP-binding cassette protein is selected from MDR-1 or Bcrp-1.
  • Multidrug resistance protein-1 MDR-1 or ABCB1 or P-glycoprotein 1 or CD243
  • breast cancer resistance protein-1 Bcrp-1 or Bcrp or ABCG2, or CD338, is very effective in promoting endothelial repair.
  • the MDR-1 specific antibody is Clone REA495.
  • Clone REA495 was purchased from Miltenyi Biotech Co., Ltd., Germany.
  • the Bcrp-1 specific antibody is Clone 5D3.
  • Clone 5D3 was purchased from Miltenyi Biotech Co., Ltd., Germany.
  • the invention also provides an implanted medical device, wherein the surface of the implanted medical device is loaded with a specific antibody of an ATP-binding box protein.
  • the ATP-binding cassette protein is selected from MDR-1 or Bcrp-1.
  • the MDR-1 specific antibody is Clone REA495.
  • the Bcrp-1 specific antibody is Clone 5D3.
  • a specific antibody of the ATP-binding cassette protein is supported on at least one side of the implanted medical device.
  • the implanted medical device is a vascular prosthesis, a prosthetic valve membrane, a prosthetic valve stent, a left atrial appendage occluder membrane, a left atrial appendage occluder stent, a heart occluder membrane, a heart occluder stent, or an artificial Patch.
  • the implanted medical device is a left atrial appendage occluder membrane or a cardiac occluder membrane.
  • the concentration range of the specific antibody of the ATP-binding cassette protein on the surface of the implanted medical device is: 10-1000 g / mm 2 .
  • concentration is too low, the antibody is quickly dissolved in the blood; when the concentration reaches a certain level, the antibody binding site is saturated, and the above effect is no longer increased.
  • the present invention also provides a method for preparing the above-mentioned implanted medical device, which comprises supporting a specific antibody of the ATP-binding box protein on at least a part of the surface of the implanted medical device and / or specificity of the ATP-binding box protein. Loaded in a hole or groove of the implanted medical device.
  • the specific antibody of the ATP-binding cassette protein is loaded on the surface of the implanted medical device by at least one of a direct coating method, a chemical grafting method, and an electrostatic adsorption method.
  • the direct coating method is to directly apply the antibody solution to the surface of the device, and the coating method may be spray coating, dip coating or spin coating.
  • the chemical grafting method may be to chemically modify the antibody molecules so that they can be chemically connected to the surface of the device or the surface of the device coating, or it may use an antibody linker or a cross-linking agent to bind the antibody molecules to the surface of the device. .
  • the electrostatic adsorption method is to coat the surface of the device with an oppositely charged coating, so that the antibody molecules are coated on the surface of the device by electrostatic adsorption.
  • the technical scheme of the present invention creatively uses the specific antibody of the ATP-binding box protein to achieve the effect of promoting endothelial repair of the medical device.
  • the technical scheme of the present invention captures the human hematopoietic stem cells and induces them to produce cells to achieve targeted endothelial repair. Therefore, the side effect of this method is small, and it will not bring other adverse effects, and the comprehensive effect is more ideal.
  • FIG. 1 is a fluorescence diagram of a sample loaded with a specific antibody of an ATP-binding box protein in a antibody loading experiment of Example 5 after staining with a secondary antibody fluorescent dye, and the three diagrams from left to right correspond to Examples 1, 2, and 4 sample;
  • FIG. 2 is a fluorescence diagram of a sample loaded with a specific antibody against an ATP-binding box protein in a cell capture experiment of Example 5 to capture cells in the blood, and the cells were fluorescently stained with specific antibody fluorescence, and the three maps from left to right correspond sequentially Samples of Examples 1, 2 and 4;
  • FIG. 3 is a SEM characterization diagram of a stent and a drug stent loaded with a specific antibody to an ATP-binding cassette protein in an animal experiment of Example 14 after implantation into the iliac artery of a rabbit 14 days, and FIG. 3a to FIG. 3c are Examples 1, 2 and 4 stent sample, Figure 3d is a stent sample of the control group;
  • Example 4 is a fluorescence diagram of the membrane of Example 3 after being stained with a secondary antibody fluorescent dye in the antibody loading experiment of Example 6;
  • Example 5 is a fluorescence diagram of a cell capture experiment in Example 6 using a membrane of Example 3 to capture cells in the blood and perform specific antibody fluorescent staining on the cells.
  • FIG. 6 is a SEM characterization image of the sample film sewn in the left atrial appendage occluder stent in the animal experiment of Example 6 14 days after implantation in the body. An untreated sample film was used as a control.
  • the "medical device” referred to in the present invention may be a device implanted in a body.
  • the device can be used temporarily for short periods or permanently implanted for long periods.
  • suitable devices are commonly used for arrhythmia, heart failure, valvular disease, vascular disease, diabetes, neurological diseases and disorders, orthopedics, neurosurgery, oncology, ophthalmology, and ENT Surgery provides medical and / or diagnostic equipment.
  • the medical devices involved in the present invention include, but are not limited to, the following devices: stents, stent grafts, anastomotic connectors, synthetic patches, leads, electrodes, needles, wires, catheters, sensors, surgical instruments, angioplasty balls, and wound drainage tubes , Shunt, tube, infusion sleeve, urethral intubation, pellet, implant, blood oxygen generator, pump, vascular graft, vascular access box port), heart valves, annuloplasty rings, sutures, surgical clips, surgical staples, pacemakers, implantable defibrillators, neurostimulators, orthopedic surgical instruments, cerebrospinal fluid shunt tubes, implantable Medication pumps, cages, artificial discs, alternative devices to the nucleus pulposus, ear canals, intraocular lenses, and any tubes used in interventional procedures.
  • the medical devices according to the present invention are in particular: stents, balloons, occluders, valves or artificial blood vessels.
  • Bcrp1 monoclonal antibody Clone 5D3 (purchased from Miltenyi Biotech Co., Ltd., Germany) was dissolved in 10 mL of antibody dilution solution (Wuhan Ph.D.) to prepare an antibody solution with a concentration of 10 g / mL.
  • Polyelectrolyte sodium hyaluronate (HA) 1mg / mL dissolved in 0.1% NaCl solution
  • polyelectrolyte chitosan (CS) 1mg / mL dissolved in 0.1% NaCl solution
  • Amine (PEI) 5 mg / mL was dissolved in a 0.1% NaCl solution.
  • PEI polyacetimide
  • HA sodium hyaluronate
  • CS chitosan
  • the stent was immersed in an antibody linker NHS (100 mM) / EDC (400 mM) solution and reacted at 4 ° C for 2 hours, then taken out into the antibody solution and reacted at 37 ° C for 2 hours, and N 2 was taken out and blow dried.
  • the preparation of the Clone 5D3 loaded scaffold was completed.
  • the concentration of Clone 5D3 on the surface of the obtained stent was 813 g / mm 2 .
  • This example is the in vivo and in vitro function evaluation of the scaffolds loaded with Clone 5D3 or Clone REA495 antibody in three ways in Examples 1, 2, and 4.
  • the antibody-loaded scaffold was fluorescently stained with a TRITC-labeled anti-mouse IgG secondary antibody to identify whether the antibody was successfully loaded.
  • FIG. 1 shows the fluorescence pictures of the samples of Example 1, Example 2, and Example 4 stained with a secondary antibody fluorescent dye in order from left to right. It can be seen from the figure that the scaffold can be stained with fluorescent colors after being loaded with antibodies. This indicates that the antibody can be successfully loaded on the surface of the scaffold.
  • the 6-well plate covered with fibronectin was used, and the antibody-supported scaffolds in Examples 1, 2, and 4 were placed in different 6-well plate wells. Take the mixed cell suspension and add 2mL of cell suspension to each well. The six-well plate was placed in a 37 ° C incubator with a CO 2 concentration of 5% with shaking culture. After 2 hours, the 6-well plate was taken out, the cells were fixed, and the cells were stained with antibody dyes (CD338-PE, CD243-PE) grafted with phycoerythrin fluorescent groups, respectively, and the cell performance was identified.
  • antibody dyes CD338-PE, CD243-PE
  • the antibody fluorescent dye CD338-PE corresponding to Bcrp-1 and the CD243-PE fluorescent dye corresponding to MDR-1 are used. Dyes can fluorescently capture captured cells. The samples in Examples 1, 2, and 4 captured cells in the blood, and the cells captured on the surface of the samples could be stained with red fluorescence by the phycoerythrin fluorescent dye.
  • Figure 2 shows the fluorescence images of the cells captured by the samples of Examples 1, 2, and 4 after specific antibody fluorescence staining in sequence from left to right, which shows that samples loaded with Bcrp1 antibody or MDR1 antibody can successfully capture hematopoietic stem cells.
  • Bcrp-1 and MDR-1 antibody-loaded scaffolds were prepared according to the methods in Examples 1, 2, and 4.
  • the tools and reagents used in the preparation process need to be sterilized beforehand, and the entire preparation process is completed in a sterile environment.
  • the obtained stent is crimped, blow molded, and packed in a sterile environment. Finally, it was stored at 4 ° C until use.
  • Each rabbit implanted a stent in the left and right iliac arteries as a parallel sample.
  • target vessels Prior to stent implantation, target vessels will be evaluated by angiography. After the stent is implanted, all target vessels will be evaluated again by angiography.
  • FIG. 3a to FIG. 3c are SEM images of the stent samples of Examples 1, 2 and 4, in order, and FIG. 3d is a SEM image of the stent samples of the control group. It can be found from FIG.
  • This example is an evaluation of the function of the left atrial appendage occluder membrane loaded with Clone REA495 in vivo and in vivo in Example 3.
  • the antibody-loaded membrane was fluorescently stained with a TRITC-labeled anti-mouse IgG secondary antibody to identify whether the antibody was successfully loaded.
  • the left atrial appendage occluder membrane can be stained with fluorescent color after being loaded with antibodies. This indicates that antibodies can be successfully loaded on the membrane surface.
  • the antibody-loaded membrane was sewn on the surface of the left atrial appendage occluder stent, and was sterilized for use.
  • Six beagle dogs with a weight of about 30 kg were prepared, and three in each of the experimental group and the control group.
  • the left atrial appendage was loaded with antibodies in the experimental group, and the left atrial appendage was untreated in the control group. After the animals were anesthetized, atrial septal puncture was performed under X-ray fluoroscopy.
  • the puncture sheath was pushed into the left atrium, the puncture needle was withdrawn, the superhard guide wire was inserted along the dilator, the left atrial appendage occluder sheath was exchanged, and a 6F pigtail catheter was sent along the sheath to the left atrial appendage for imaging.
  • an occluder of appropriate specifications was selected for implantation in the left atrial appendage, and the occlusive effect was observed by angiography and the occlusion stability was tested by traction. If the occlusion effect is good and the occluder is stable, release the occluder. Withdraw the sheath tube and complete the operation to complete the left atrial appendage occluder implantation operation.
  • the left atrial appendage occluder was dissected out and the left atrial appendage occluder membrane was removed from the stent. After fixation and dehydration, the endothelialization of the membrane surface was observed by SEM. As shown in FIG. 6, the left picture is the sample film loaded with Clone REA 495 in Example 3, and the right picture is the untreated sample film in the control group. The image on the left shows that the membrane surface is completely covered by endothelial cells after the antibody is loaded, and the image on the right shows a large amount of fibrin and blood cells deposited on the untreated membrane surface. This shows that the left atrial appendage occluder using an antibody-loaded membrane can rapidly achieve endothelialization.
  • the technical scheme provided by the present invention creatively uses the specific antibody of the ATP-binding box protein to achieve the effect of promoting endothelial repair of the medical device.
  • the technical scheme provided by the present invention captures the human hematopoietic stem cells and induces them to produce cells to achieve targeted endothelial repair. Therefore, the side effect of this method is small, and it will not bring other adverse effects, and the comprehensive effect is more ideal.

Abstract

Applications d'un anticorps spécifique, instrument médical implantable et procédé de préparation associé. Les applications se réfèrent aux applications d'un anticorps spécifique d'un tranporteur ABC dans la préparation d'un médicament destiné à favoriser la cicatrisation endothéliale. La surface de l'instrument médical implantable est chargée avec l'anticorps spécifique du transporteur ABC. Le procédé de préparation comprend la charge de l'anticorps spécifique du transporteur ABC sur au moins une partie de la surface de l'instrument médical implantable, et/ou la liaison de l'anticorps chargé du transporteur ABC dans le trou ou la rainure ménagée dans l'instrument médical implantable.
PCT/CN2019/096999 2018-07-27 2019-07-22 Applications d'un anticorps spécifique, instrument médical implantable et procédé de préparation associé WO2020020089A1 (fr)

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CN201810847147.2 2018-07-27
CN201810847147.2A CN110755609A (zh) 2018-07-27 2018-07-27 一种特异性抗体的用途、一种植入医疗器械及其制备方法

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Publication number Priority date Publication date Assignee Title
CN112472878A (zh) * 2020-12-10 2021-03-12 上海锦葵医疗器械股份有限公司 一种含复合涂层的封堵器及其制备方法
CN112472156A (zh) * 2020-12-10 2021-03-12 上海锦葵医疗器械股份有限公司 一种含药物涂层的封堵器及其制备方法
CN112426185A (zh) * 2020-12-10 2021-03-02 上海锦葵医疗器械股份有限公司 一种含可膨胀涂层的封堵器及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006014157A1 (fr) * 2004-07-01 2006-02-09 Macropore Biosurgery Inc. Procedes utilisant des cellules regeneratives pour favoriser la guerison des plaies
CN101172168A (zh) * 2007-10-10 2008-05-07 大连理工大学 胺糖聚糖负载cd133抗体的金属血管支架涂层与制法
CN102399741A (zh) * 2010-09-19 2012-04-04 林雄斌 逆向分化体细胞产生造血干细胞的培养液、方法及用途

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8372399B2 (en) * 2006-08-31 2013-02-12 Cardiac Pacemakers, Inc. Bispecific antibodies and agents to enhance stem cell homing
US8512696B2 (en) * 2007-11-30 2013-08-20 Autologous, Llc Methods of isolating non-senescent cardiac stem cells and uses thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006014157A1 (fr) * 2004-07-01 2006-02-09 Macropore Biosurgery Inc. Procedes utilisant des cellules regeneratives pour favoriser la guerison des plaies
CN101172168A (zh) * 2007-10-10 2008-05-07 大连理工大学 胺糖聚糖负载cd133抗体的金属血管支架涂层与制法
CN102399741A (zh) * 2010-09-19 2012-04-04 林雄斌 逆向分化体细胞产生造血干细胞的培养液、方法及用途

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
"Medical Application of Hemopoietic Stem Cell Gains New Breakthrough", JOURNAL OF FRONTIERS OF MEDICINE, vol. 5, no. 23, 31 August 2015 (2015-08-31) *
M. H. G. P. RAAIJMAKERS: "ATP-binding-cassette transporters in hematopoietic stem cells and their utility as therapeutical targets in acute and chronic mye- loid leukemia", LEUKEMIA, vol. 27, no. 10, 1 October 2007 (2007-10-01), pages 2094 - 2102, XP055681648 *
WU, XUAN ET AL.: "Comparative Study of Different Monoclonal Antibodies for P-glycoprotein in ColonCarcinoma", JOURNAL OF SHANTOU UNIVERSITY MEDICAL COLLEGE, vol. 20, no. 4, 31 December 2007 (2007-12-31), pages 226 - 227 *
ZHAO, YACHAO ET AL: "Research Advance of Breast Cancer Resistance Protein", PROGRESS IN MODERN BIOMEDICINE, vol. 10, no. 2, 31 January 2010 (2010-01-31), pages 369 - 371 *

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