[go: up one dir, main page]

WO2006114805A2 - Utilisation des proteines hmgb2 et hmgb3 pour applications medicales - Google Patents

Utilisation des proteines hmgb2 et hmgb3 pour applications medicales Download PDF

Info

Publication number
WO2006114805A2
WO2006114805A2 PCT/IT2006/000293 IT2006000293W WO2006114805A2 WO 2006114805 A2 WO2006114805 A2 WO 2006114805A2 IT 2006000293 W IT2006000293 W IT 2006000293W WO 2006114805 A2 WO2006114805 A2 WO 2006114805A2
Authority
WO
WIPO (PCT)
Prior art keywords
hmgb2
hmgb3
cells
protein
hmgbl
Prior art date
Application number
PCT/IT2006/000293
Other languages
English (en)
Other versions
WO2006114805A3 (fr
Inventor
Marco Bianchi
Tobias Pusterla
Original Assignee
Fondazione Centro San Raffaele Del Monte Tabor
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 Fondazione Centro San Raffaele Del Monte Tabor filed Critical Fondazione Centro San Raffaele Del Monte Tabor
Publication of WO2006114805A2 publication Critical patent/WO2006114805A2/fr
Publication of WO2006114805A3 publication Critical patent/WO2006114805A3/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • C07K14/4703—Inhibitors; Suppressors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • HMGBs High Mobility Group Box proteins
  • HMG box A and B basic DNA binding domains
  • HMGB2 High Mobility Group Box proteins
  • HMGB3 Three proteins (HMGBl, HMGB2 and HMGB3) with a highly conserved structure (80% amino acid identity) (Agresti 2003).
  • HMGB l's expression is almost ubiquitous (Calogero, 1999), while HMGB2 is widely expressed during embryonic development (Ronfani,
  • HMGB3 appears to be highly expressed during embryo development and in hemopoietic stem cells (Nemeth, 2004). The author's group already demonstrated that HMGBl is released by necrotic cells (Scaff ⁇ di,
  • HMGB2 is able to promote proliferation and migration of bovine aortic endothelial cells (BAEC).
  • BAEC bovine aortic endothelial cells
  • RAGE may have different applications.
  • HMGB3 protein or functional part thereof exerting a chemoattracting and not a proliferating activity for medical use.
  • the protein or functional part thereof is able to exert a chemoattractive activity of cells able to restore a missed function (i.e. adult stem cells) and can be used for disease treatment.
  • the chemoattracting portion is comprised in the region between Box B (aa. 80-180) and the acidic tail of HMGB2; by sequence comparison HMGB3 chemoattracting region is comprised in the same region, preferably between aa. 166- 181.
  • the HMGB3 protein or functional part thereof exerting a chemoattracting and not a proliferating activity is also advantageously used for the preparation of an immunostimulating composition, being able to attract immunomodulating cells.
  • the HMGB3 protein or functional part thereof acts as adjuvant.
  • the immunostimulating composition is a vaccine.
  • a pharmaceutical composition comprising an effective amount of the HMGB3 protein or functional part thereof exerting a chemoattracting and not a proliferating activity.
  • an immunostimulating composition comprising an effective amount of the HMGB 3 protein or functional part thereof exerting a chemoattracting and not a proliferating activity, preferably a vaccine composition.
  • the invention refers also to the use of the HMGB2 protein or functional part thereof for the preparation of an activating cell proliferation pharmaceutical composition, preferably for tissue regeneration, more preferably for myocardial tissue regeneration and/or peripheral artery diseases, alternatively for wound healing.
  • FIG. 1 HMGB2 expression. HMGB2 is expressed and secreted in activated monocytes. A: immuno-staining for HMGB2, B: immuno-staining for HMGBl, C: merge HMGB1-HMGB2, D: DAPI, E: western blot for HMGB2 and actin on LPS treated and untreated monocytes.
  • FIG. 2 Effect of HMGBs on bovine aortic endothelial cells proliferation.
  • BAEC were grown in DMEM Medium containing no addition, 30 ng/ml of HMGBl, HMGB2 and HMGB3 each. Cells were counted At 24, 48 and 72h. HMGBl and HMGB2 induced cell proliferation while HMGB3 shows growth comparable to serum free cells. The experiment was repeated three times.
  • FIG. 3 HMGB2 chemotactic activity on BAEC.
  • BAEC were subjected to chemotaxis assays with 1, 3,10, 30, 100 ng/ml HMGB2.
  • HMGB2 shows concentration-dependent chemoattractant effect on endothelial cells.
  • Figure 4 Chemotactic effect of HMGB2 fragments on bovine aortic endothelial cells.
  • a BAEC were subjected to chemotaxis assays with HMGB2 Box A (1-80), Box B (80-180), HMGB2A+B (1-180) and the wild type protein at 0.1, 1, 10, 100 ng/ml of concentration each.
  • HMGB2A+B and Box B have a chemotactic effect comparable to wt HMGB2. In contrast Box A has no significant chemotactic activity.
  • B Schematic representation of wt full length, tailless (HMGB2A+B), Box A and Box B HMGB2 fragments tested for migration assay.
  • Figure 5 Chemotactic effect of HMGb3 on bovine aortic endothelial cells. BAEC were subjected to chemotaxis assays with 1, 3, 10, 30, 100 ng/ml of HMGB3. HMGB3 has a chemotactic effect on cells although it seems not comparable to HMGBl and HMGB2.
  • HMGB3 shows migration-inducing ability at a ten fold lower concentration compared to other HMGBs although the amount of cells migrating per field is lower compared to other HMGBs.
  • Figure 6 Chemotactic effect of HMGBs on bovine aortic endothelial cells. Migration assay was performed with the most migration-promoting concentration of each protein: HMGBl (30ng/ml),HMGB2 (3ng/ml) and HMGB3 (lng/ml).
  • FIG. 7 Antibody against HMGB2 blocks BAEC migration.
  • Treatment with lOOng of HMGB2 antibody shows basal levels of endothelial cells migration.
  • B shows migration assay with increasing concentrations of HMGB2 (1, 3, 10, 30, 100 ng/ml) with or without lOOng of blocking anti-HMGB2 anibody.
  • Figure 8 BAEC over-expressing dominant negative RAGE loose their migrating ability.
  • a BAEC cotransfected with dn-RAGE expressing plasmid or control pCDNA3 and YFP expressing plasmid in a 1:3 ratio were assayed for chemotaxis in response to 20% serum, 30ng/ml of HMGB2 and lng/ml of HMGB3.
  • Cells transfected with dn-RAGE exhibited a significant decrease in migration in comparison to cells transfected with control plasmid pCDNA3.
  • FIG. 9 Residues 1-300 of RAGE present on BAEC cell membrane was blocked. Chemotaxis was performed with HMGBl (30ng/ml), HMGB2 (3ng/ml) and HMGB3 (lng/ml).BAEC in the upper compartment were added of l ⁇ g of anti-RAGE H300 antibody. Cells whose receptor is blocked by H300 antibody show basal levels of migration compared to untreated cells.
  • Figure 10 Human and murine HMGBs alignment.
  • Bovine Aorta Endothelial Cells were isolated from a section of the thoracic aorta of a freshly slaughtered calf as described (Palumbo et al., 2002).
  • Mouse monocytes were obtained by intraperitoneal washes and cultured in RPMI medium additioned with 10% FCS. Cells were stimulated with lO ⁇ g/ml of LPS for 16 hours.
  • HMGB2 and HMGB3 protein and fragments thereof were performed as described previously for HMGBl (Muller et al., 2001). Endotoxins were removed by passage through Detoxy-Gel columns (Pierce). Rabbit polyclonal anti-HMGBl and HMGB2 antibodies were from Pharmingen BD, polyclonal antibodies against HMGBl were from MBL, anti-RAGE H300 rabbit antibody was from Santa Cruz.
  • LPS-stimulated monocytes were fixed in 4% paraformaldehyde, permeabilized, saturated and processed for immunofluorescence with mouse monoclonal anti-HMGBl (dilution 1:500) and rabbit anti-HMGB2 antibody (dilution 1:1000) followed by Alexa Fluor 488/546-conjugated anti-rabbit/anti-mouse Ig (Molecular Probes). Images were taken with a Zeiss SlOO TV microscope equipped with a Zeiss 32x/ 0.4 Ph2 LD Achroplane objective. Proliferation assay
  • Chemotaxis blocking- experiments were performed by adding in the lower chamber 30ng/ml of HMGB2 and 0.001, 0.01, 0.1, 1, lO ⁇ g of anti-HMGB2 antibody or in the upper chamber l ⁇ g of anti-RAGE antibody.
  • BAEC cells were grown in DMEM plus 10% FCS, starved overnight, washed twice with PBS to eliminate any floating cells, and harvested with trypsin.
  • Fifty thousand cells resuspended in 200 ⁇ l DMEM were placed in the upper chambers and incubated at 37°C in 5% CO 2 for 5 h.
  • Dominant negative RAGE is a RAGE truncation lacking the entire intracytoplasmic domain (Hofmann et al., 1999).
  • One million BAEC cells were co-transfected with 1 mg pNLSl-YFP (pNLSl-YFP was constructed like pNLSl-GFP (Bonaldi, 2003)) and 3 mg of plasmid encoding dominant negative RAGE (dnRAGE) or pCDNA3 empty vector, using FuGene reagent (Roche). After 24 hours, the medium was replaced with DMEM plus 10% FCS; after additional 24 hours the chemotaxis assay was carried out as described above. Only YFP- positive cells were considered. Protein alignment
  • HMGB2 is expressed in monocytes
  • Mouse monocytes were obtained with intra-peritoneal washes of wild type c57bl/6 mice. Cells seeded were cultured with RPMI medium and activated with LPS. hnmuno-fluorescence assay with anti-HMGB2 antibody was performed on activated monocytes.
  • Fig. 1 shows how HMGB2 is expressed in mouse monocytes at nuclear level. Furthermore HMGB2 is also present in localized spots in the cytosol, suggesting a relocalization from the nucleus into secretory vesicles in the activated cells. ESTs analysis and RT-PCR confirmed HMGB2 expression in myeloid cells.
  • HMGB2 stimulates endothelial cells proliferation ( " not HMGB3)
  • Endothelial cells were taken from aorta of adult bovines. Primary colture cells were seeded in
  • HMGBl was able to promote mesangioblast proliferation 24h after the stimulus, whereas only slight proliferation was seen at 48 and 72h. These cells exposed every 24h to HMGBl continued to proliferate, suggesting a depletion of the protein present in the medium. Our data suggest that BAEC do not deplete the stimulus from the medium or have a prolonged response to it. Although Bl and B2 curves were comparable (Fig.2), BAEC had a higher response to HMGBl suggesting its higher activity. Fig.2 shows clearly that HMGB3 has no proliferating effect: stimulated cells show levels comparable to serum free treated cells over the 72h assay.
  • HMGBl and HMGB2 act as growth factors for endothelial cells and suggest that different cell types may have different proliferating responses to these proteins.
  • HMGB3 showed no proliferating effect although HMGBs share 80% homology of sequence suggesting that these proteins are only partially redundant.
  • HMGB2 induces BAEC migration
  • HMGBl acts not only as proliferating stimulus but as a chenioattractant for mouse mesangioblasts too (Palumbo, 2004), hence we investigated whether HMGB2 and HMGB3 could share the same capability.
  • Fig 3 shows how in a chemotaxis assay using modified Boyden chambers, HMGB2 stimulates migration of bovine endothelial cells.
  • BAEC responded to protein concentrations raging from 1 ng/nil to 100 ng/ml in a concentration-dependent way. The migration peak was seen at 3-10 ng/ml of HMGB2.
  • HMGB2 domains were also tested for their ability to promote cell migration (fig.4A).
  • HMGB2A+B the protein lacking the acidic tail (residues 1-180), showed a slightly higher capability of promoting cell migration compared to the wild type protein.
  • HMGB2 Box B (residues 80-180) showed a behavior comparable to HMGB2A+B.
  • HMGB2 Box A alone (1-80) induced basal levels of migration.
  • the active portion of the protein should be thus limited in the region between Box B and the acidic-tail-upstream linker region.
  • HMGBl and HMGB2's data show a similar action of the two proteins although, utilizing same concentrations, cells seem to be more responsive towards HMGB2's stimulus.
  • a migration assay was set up utilizing each protein at its migration-promoting peak concentration: 30 ng/ml HMGBl, 3 ng/ml HMGB2 and 1 ng/ml HMGB3.
  • Fig. 6 shows the migratory effect of HMGBs: at their peak HMGBl and HMGB2 seem to have the same activity whereas HMGB3 seems a little less active working at a lower concentration.
  • Anti-HMGB2 blocks cell migration
  • Residues 150-183, the linker region between box B and the acidic tail, were identified as the HMGBl segment promoting migration through its interaction with RAGE (Huttunen, 2002).
  • HMGB2 polyclonal antibody specifically recognizes as epitope the amino acid stretch comprised between HMGB2 box B and the acidic tail (residues 166 and 181) which is the likely region implied in chemotaxis.
  • HMGB2's activity is comparable to HMGBl, we performed a chemotactic assay using HMGB2 blocked by an anti-HMGB2 antibody.
  • Fig. 7 shows blocking assays on cell migration. Two kinds of experiments were performed.
  • HMGB2 concentration 30ng/ml to find the antibody blocking concentration (Fig. 7A).
  • lOOng of anti-HMGB2 antibody was seen to be the optimal amount inhibiting cell migration.
  • a second migration assay was performed with increasing concentrations of HMGB2 and lOOng of blocking anti-HMGB2 antibody.
  • HMGBl and HMGB2's proven redundancy suggest that HMGB2 chemoattractant function should be mediated by the binding with RAGE such as with HMGBl(Huttunen, 2002).
  • RAGE advanced-end glycosylation end products
  • RAGE is able to promote endothelial cell migration via its binding with all three members of the HMGB family.
  • RAGE extracellular portion is composed of 400 residues, blockage of this portion should inactivate the receptor because of the occlusion of the binding domain and thus not induce the activation of the migratory pathway.
  • HMGBs In order to confirm RAGE-HMGBs interaction a migration assay was performed. HMGBs, each used at its highest migration-promoting concentration (30 ng/ml HMGBl, 3 ng/ml HMGB2 and 1 ng/ml HMGB3), were used as chemotactants. Bovine aortic endothelial cells were treated with 1 ⁇ g of H300, a polyclonal antibody that recognizes and binds the first 300 residues of the extracellular portion of RAGE.
  • the migration assay shows that H300-treated BAEC lose their ability to respond to the
  • HMGBs chemotactic stimulus cells with blocked-RAGE in the presence of HMGBl, HMGB2 or HMGB3 show basal levels of migration, whereas untreated cells do migrate (Fig
  • HMG high mobility group
  • the receptor for advanced glycation end products is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J Biol Chem. 1995 Oct 27;270(43):25752-61. Huttunen HJ, Fages C, Kuja-Panula J, Ridley AJ, Rauvala H. Receptor for advanced glycation end products-binding COOH-terminal motif of amphoterin inhibits invasive migration and metastasis.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Toxicology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention porte sur la protéine HMGB3 ou sur une partie fonctionnelle de celle-ci exerçant une attraction chimique et non une activité proliférative, cette protéine étant destinée à un usage médical et ayant une activité immunostimulatrice. L'invention porte également sur la protéine HMGB2 ou sur une partie fonctionnelle de celle-ci, cette protéine étant utile dans la préparation d'une composition pharmaceutique activant la prolifération cellulaire.
PCT/IT2006/000293 2005-04-28 2006-04-28 Utilisation des proteines hmgb2 et hmgb3 pour applications medicales WO2006114805A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US67550805P 2005-04-28 2005-04-28
US60/675,508 2005-04-28

Publications (2)

Publication Number Publication Date
WO2006114805A2 true WO2006114805A2 (fr) 2006-11-02
WO2006114805A3 WO2006114805A3 (fr) 2007-03-01

Family

ID=36754170

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IT2006/000293 WO2006114805A2 (fr) 2005-04-28 2006-04-28 Utilisation des proteines hmgb2 et hmgb3 pour applications medicales

Country Status (1)

Country Link
WO (1) WO2006114805A2 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009133939A1 (fr) * 2008-04-30 2009-11-05 株式会社ジェノミックス Agent de recrutement d'une cellule souche pluripotente issue de la moelle osseuse dans la circulation périphérique
WO2012034090A1 (fr) * 2010-09-09 2012-03-15 University Of Southern California Compositions et procédés pour éliminer des biofilms
CN102899396A (zh) * 2012-07-25 2013-01-30 山东省农业科学院奶牛研究中心 影响奶牛乳腺炎易感/抗性hmgb3基因的核心启动子及其功能性分子标记与应用
US8999291B2 (en) 2010-03-29 2015-04-07 University Of Southern California Compositions and methods for the removal of biofilms
US9623078B2 (en) 2012-10-25 2017-04-18 Genomix Co., Ltd. Method for treating cardiac infarction using HMGB1 fragment
US9688733B2 (en) 2012-10-25 2017-06-27 Genomix Co., Ltd. Method for treating spinal cord injury using HMGB1 fragment
US9745366B2 (en) 2013-09-23 2017-08-29 University Of Southern California Compositions and methods for the prevention of microbial infections
US9919010B2 (en) 2008-04-30 2018-03-20 Genomix Co., Ltd. Method for collecting functional cells in vivo with high efficiency
US10233234B2 (en) 2014-01-13 2019-03-19 Trellis Bioscience, Llc Binding moieties for biofilm remediation
US10364276B2 (en) 2011-04-26 2019-07-30 StemRIM Inc. Peptide for inducing regeneration of tissue and use thereof
US10940204B2 (en) 2015-07-31 2021-03-09 Research Institute At Nationwide Children's Hospital Peptides and antibodies for the removal of biofilms
US11191786B2 (en) 2009-10-28 2021-12-07 StemRIM Inc. Agents for promoting tissue regeneration by recruiting bone marrow mesenchymal stem cells and/or pluripotent stem cells into blood
US11248040B2 (en) 2013-09-26 2022-02-15 Trellis Bioscience, Llc Binding moieties for biofilm remediation
US11274144B2 (en) 2013-06-13 2022-03-15 Research Institute At Nationwide Children's Hospital Compositions and methods for the removal of biofilms
US11298403B2 (en) 2017-12-01 2022-04-12 StemRIM Inc. Therapeutic agent for inflammatory bowel disease
US11746136B2 (en) 2017-03-15 2023-09-05 Research Institute At Nationwide Children's Hospital Composition and methods for disruption of bacterial biofilms without accompanying inflammation
US11969459B2 (en) 2017-01-27 2024-04-30 StemRIM Inc. Therapeutic agent for cardiomyopathy, old myocardial infarction and chronic heart failure

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002074337A1 (fr) * 2001-03-16 2002-09-26 Bio3 Research S.R.L. Inhibiteurs et/ou antagonistes de proteines hmgb1 destines au traitement de maladies vasculaires
WO2004046338A2 (fr) * 2002-11-20 2004-06-03 North Shore-Long Island Jewish Research Institute Utilisation de polypeptides hmgb permettant d'accroitre des reponses immunitaires

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002074337A1 (fr) * 2001-03-16 2002-09-26 Bio3 Research S.R.L. Inhibiteurs et/ou antagonistes de proteines hmgb1 destines au traitement de maladies vasculaires
WO2004046338A2 (fr) * 2002-11-20 2004-06-03 North Shore-Long Island Jewish Research Institute Utilisation de polypeptides hmgb permettant d'accroitre des reponses immunitaires

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HUTTUNEN HENRI J ET AL: "Receptor for advanced glycation end products-binding COOH-terminal motif of amphoterin inhibits invasive migration and metastasis." CANCER RESEARCH. 15 AUG 2002, vol. 62, no. 16, 15 August 2002 (2002-08-15), pages 4805-4811, XP002394355 ISSN: 0008-5472 cited in the application *
NEMETH MICHAEL J ET AL: "Hmgb3 deficiency deregulates proliferation and differentiation of common lymphoid and myeloid progenitors." BLOOD. 15 JAN 2005, vol. 105, no. 2, 15 January 2005 (2005-01-15), pages 627-634, XP002394354 ISSN: 0006-4971 cited in the application *
TERADA ET AL: "Nucleosome regulator Xhmgb3 is required for cell proliferation of the eye and brain as a downstream target of Xenopus rax/Rx1" DEVELOPMENTAL BIOLOGY, ACADEMIC PRESS, NEW YORK, NY, US, vol. 291, no. 2, 15 March 2006 (2006-03-15), pages 398-412, XP005338138 ISSN: 0012-1606 *

Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9919010B2 (en) 2008-04-30 2018-03-20 Genomix Co., Ltd. Method for collecting functional cells in vivo with high efficiency
US8673580B2 (en) 2008-04-30 2014-03-18 Genomix Co., Ltd. Agent for recruitment of bone-marrow-derived pluripotent stem cell into peripheral circulation
US11197895B2 (en) 2008-04-30 2021-12-14 StemRIM Inc. Method for collecting functional cells in vivo with high efficiency
WO2009133939A1 (fr) * 2008-04-30 2009-11-05 株式会社ジェノミックス Agent de recrutement d'une cellule souche pluripotente issue de la moelle osseuse dans la circulation périphérique
AU2009240884B2 (en) * 2008-04-30 2014-02-13 Genomix Co., Ltd. Agent for recruitment of bone-marrow-derived pluripotent stem cell into peripheral circulation
AU2009240884B8 (en) * 2008-04-30 2014-03-06 Genomix Co., Ltd. Agent for recruitment of bone-marrow-derived pluripotent stem cell into peripheral circulation
AU2009240884A8 (en) * 2008-04-30 2014-03-06 Genomix Co., Ltd. Agent for recruitment of bone-marrow-derived pluripotent stem cell into peripheral circulation
JP2015038094A (ja) * 2008-04-30 2015-02-26 株式会社ジェノミックス 末梢循環への骨髄由来多能性幹細胞動員薬
RU2519714C2 (ru) * 2008-04-30 2014-06-20 Дженомикс Ко., Лтд. Средство для вовлечения происходящей из костного мозга плюрипотентной стволовой клетки в периферический кровоток
JP5660889B2 (ja) * 2008-04-30 2015-01-28 株式会社ジェノミックス 末梢循環への骨髄由来多能性幹細胞動員薬
US11191786B2 (en) 2009-10-28 2021-12-07 StemRIM Inc. Agents for promoting tissue regeneration by recruiting bone marrow mesenchymal stem cells and/or pluripotent stem cells into blood
US8999291B2 (en) 2010-03-29 2015-04-07 University Of Southern California Compositions and methods for the removal of biofilms
WO2012034090A1 (fr) * 2010-09-09 2012-03-15 University Of Southern California Compositions et procédés pour éliminer des biofilms
AU2011299025B2 (en) * 2010-09-09 2015-07-09 Nationwide Children's Hospital, Inc. Compositions and methods for the removal of biofilms
US10595530B2 (en) 2010-09-09 2020-03-24 Nationwide Children's Hospital, Inc. Compositions and methods for the removal of biofilms
JP2013542185A (ja) * 2010-09-09 2013-11-21 ユニバーシティー オブ サザン カリフォルニア バイオフィルムを除去するための組成物および方法
US10550165B2 (en) 2011-04-26 2020-02-04 StemRIM Inc. Peptide for inducing regeneration of tissue and use thereof
US10364276B2 (en) 2011-04-26 2019-07-30 StemRIM Inc. Peptide for inducing regeneration of tissue and use thereof
CN102899396A (zh) * 2012-07-25 2013-01-30 山东省农业科学院奶牛研究中心 影响奶牛乳腺炎易感/抗性hmgb3基因的核心启动子及其功能性分子标记与应用
US9688733B2 (en) 2012-10-25 2017-06-27 Genomix Co., Ltd. Method for treating spinal cord injury using HMGB1 fragment
US9623078B2 (en) 2012-10-25 2017-04-18 Genomix Co., Ltd. Method for treating cardiac infarction using HMGB1 fragment
US12221472B2 (en) 2013-06-13 2025-02-11 Research Institute At Nationwide Children's Hospital Compositions and methods for the removal of biofilms
US11629182B2 (en) 2013-06-13 2023-04-18 Research Institute Of Nationwide Children's Hospital Compositions and methods for the removal of biofilms
US11274144B2 (en) 2013-06-13 2022-03-15 Research Institute At Nationwide Children's Hospital Compositions and methods for the removal of biofilms
US9745366B2 (en) 2013-09-23 2017-08-29 University Of Southern California Compositions and methods for the prevention of microbial infections
US11248040B2 (en) 2013-09-26 2022-02-15 Trellis Bioscience, Llc Binding moieties for biofilm remediation
US12152068B2 (en) 2013-09-26 2024-11-26 Trellis Bioscience, Llc Binding moieties for biofilm remediation
US10570193B2 (en) 2014-01-13 2020-02-25 Trellis Bioscience, Llc Binding moieties for biofilm remediation
US10233234B2 (en) 2014-01-13 2019-03-19 Trellis Bioscience, Llc Binding moieties for biofilm remediation
US10940204B2 (en) 2015-07-31 2021-03-09 Research Institute At Nationwide Children's Hospital Peptides and antibodies for the removal of biofilms
US11684673B2 (en) 2015-07-31 2023-06-27 Research Institute At Nationwide Children's Hospital Peptides and antibodies for the removal of biofilms
US12239763B2 (en) 2015-07-31 2025-03-04 Research Institute At Nationwide Children's Hospital Peptides and antibodies for the removal of biofilms
US11969459B2 (en) 2017-01-27 2024-04-30 StemRIM Inc. Therapeutic agent for cardiomyopathy, old myocardial infarction and chronic heart failure
US11746136B2 (en) 2017-03-15 2023-09-05 Research Institute At Nationwide Children's Hospital Composition and methods for disruption of bacterial biofilms without accompanying inflammation
US11298403B2 (en) 2017-12-01 2022-04-12 StemRIM Inc. Therapeutic agent for inflammatory bowel disease

Also Published As

Publication number Publication date
WO2006114805A3 (fr) 2007-03-01

Similar Documents

Publication Publication Date Title
WO2006114805A2 (fr) Utilisation des proteines hmgb2 et hmgb3 pour applications medicales
US11026994B2 (en) Syndecan-2 compositions and methods of use
AU2002247977B2 (en) HMGB1 protein inhibitors and/or antagonists for the treatment of vascular diseases
Hugo et al. Thrombospondin 1 is expressed by proliferating mesangial cells and is up-regulated by PDGF and bFGF in vivo
US20060111287A1 (en) Acetylated protein
US11274131B2 (en) IgM-mediated receptor clustering and cell modulation
KR20060089732A (ko) Ｔｉｍ-3 리간드 및 그의 방법
CZ295997B6 (cs) Farmaceutický prostředek s obsahem ligandu Notch a způsob tvorby T-buněk
Shivshankar et al. In response to complement anaphylatoxin peptides C3a and C5a, human vascular endothelial cells migrate and mediate the activation of B‐cells and polarization of T‐cells
PT2071028E (pt) Péptido antigénico de ligação a hla-dr derivado de wt1
TW201900212A (zh) 使用可溶性ｃｄ２４治療癌症療法中之免疫相關不良事件的方法
WO2018204829A1 (fr) Procédés pour empêcher des défauts de tube neural dans une grossesse diabétique
WO2006057027A1 (fr) Epitopes antigeniques de l'interleukine-21, anticorps correspondants et leur utilisation dans le domaine medical
US20080227745A1 (en) Methods and compositions for soluble CPG15
AU2004257830A1 (en) Regulatory T-cells containing galectins for the therapy and diagnosis of diseases
CN105121463B (zh) 肽
KR20140071565A (ko) 인간 카텔리시딘 ｌｌ―37을 포함하는 경구 백신용 보조제
ES2495430T3 (es) Una forma de PRELP de 38 KDA como nuevo diagnóstico y objetivo terapéutico
AU2322799A (en) Therapeutic blockade of icer synthesis to prevent icer-mediated inhibition of immune cell activity
WO2018231743A1 (fr) Thérapie ciblée de protéine kinase c-delta pour traiter une lésion de rayonnement
Inflammation Interactions between CD47 and
JP2012131711A (ja) カルモジュリン様皮膚タンパク質を有効成分として含む医薬組成物
HENG INVESTIGATION OF C1Q REGULATION OF MONOCYTE DEVELOPMENT
HIRATA et al. The translation elongation factor eBF2 is a novel tumor-associated antigen overexpressed in various types of cancers
Alexander Ly6A/stem cell antigen-1 and the humoral immune response

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase in:

Ref country code: DE

WWW Wipo information: withdrawn in national office

Country of ref document: DE

NENP Non-entry into the national phase in:

Ref country code: RU

WWW Wipo information: withdrawn in national office

Country of ref document: RU

122 Ep: pct application non-entry in european phase

Ref document number: 06728545

Country of ref document: EP

Kind code of ref document: A2