WO2011060349A1 - Procédés de modulation de cellules souches mésenchymateuses - Google Patents

Procédés de modulation de cellules souches mésenchymateuses Download PDF

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Publication number
WO2011060349A1
WO2011060349A1 PCT/US2010/056684 US2010056684W WO2011060349A1 WO 2011060349 A1 WO2011060349 A1 WO 2011060349A1 US 2010056684 W US2010056684 W US 2010056684W WO 2011060349 A1 WO2011060349 A1 WO 2011060349A1
Authority
WO
WIPO (PCT)
Prior art keywords
peptide
seq
myristoyl
migration
amino acid
Prior art date
Application number
PCT/US2010/056684
Other languages
English (en)
Inventor
Arnold R. Brody
Kenneth B. Adler
Indu Parikh
Original Assignee
North Carolina State University
Biomarck Pharmaceuticals, Ltd.
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 North Carolina State University, Biomarck Pharmaceuticals, Ltd. filed Critical North Carolina State University
Publication of WO2011060349A1 publication Critical patent/WO2011060349A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • 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
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10—Peptides having 12 to 20 amino acids
    • 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
    • C12N5/0662—Stem cells
    • C12N5/0663—Bone marrow mesenchymal stem cells (BM-MSC)
    • 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
    • C12N2501/998—Proteins not provided for elsewhere

Definitions

  • MSCs such as primary bone marrow MSCs (BM-
  • the migration-modulating peptide is a MANS peptide, N-myristoyl-GAQFSKTAA GEAAAERPGEAAVA (SEQ ID NO: 1).
  • mesenchymal stem cells subsequent to treatment (or pretreatment) of unmodified MSCs with an active peptide of this invention prior to measurement of the number of migrated treated MSCs in a field of measurement after a period of time in comparison to a similar measurement of number of cells in the same field in a control or reference migration of untreated MSCs for the same period of time. Attenuation of migration obtains when fewer cells of peptide-treated MSCS are observed per field of measurement compared to the number of cells per field observed in a control of untreated MSCs.
  • modulated preferably means "attenuated” or “reduced” or “inhibited” and the term “modulating” preferably means “attenuating” or "reducing” or “inhibiting.”
  • the migration-modulating peptide can be an N-terminal- and/or C-terminal-chemically modified peptide, which modified peptide consists of an active fragment amino acid sequence of MANS peptide, which peptide consists of an amino acid sequence selected from the group consisting of:
  • Figure 2 A illustrates a determination of an optimum chemokine SDF-1 concentration for mouse BM-MSC migration in vitro.
  • Bar number 23 shows a mean number of 24 cells per field related to use of 25 ng/mL SDF-1 ;
  • bar number 24 shows a mean number of 14 cells per field related to use of 50 ng/mL SDF-1 ;
  • bar number 25 shows a mean number of 6 cells per field related to use of 100 ng/mL SDF-1.
  • Bar number 43 shows a mean number of 38 cells per field related to use of 0.5 ng/mL SCF; bar number 44 shows a mean number of 30 cells per field related to use of 5 ng/mL SCF; bar number 45 shows a mean number of 34 cells per field related to use of 25 ng/mL SCF; bar number 46 shows a mean number of 16 cells per field related to use of 50 ng/mL SCF; and bar number 47 shows a mean number of 6 cells per field related to use of 100 ng/mL SCF.
  • Bar 40 (mean ⁇ 0 cells) and bar 41 (mean ⁇ 3 cells) are related to SF-IMDM and represent negative or random movement controls.
  • Mouse BM-MSCs were grown to 70% surface coverage in T-150 cm flasks (Corning), then incubated for 12 hours in serum-free (SF-) IMDM media. Once the incubation period was complete, cells were treated with Trypsin-EDTA (Invitrogen), pelleted, and enumerated using 0.4% trypan blue stain in conjunction with a

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Genetics & Genomics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Zoology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Wood Science & Technology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Rheumatology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Toxicology (AREA)
  • Cell Biology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne des procédés de modulation de la migration d'une cellule souche mésenchymateuse (MSC) comprenant la mise en contact ou le mélange d'une quantité inhibitrice de migration d'un peptide inhibiteur de migration avec la MSC pour former une MSC à migration inhibée et l'administration de la MSC à migration inhibée à un sujet nécessitant un traitement.
PCT/US2010/056684 2009-11-13 2010-11-15 Procédés de modulation de cellules souches mésenchymateuses WO2011060349A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US26113209P 2009-11-13 2009-11-13
US61/261,132 2009-11-13

Publications (1)

Publication Number Publication Date
WO2011060349A1 true WO2011060349A1 (fr) 2011-05-19

Family

ID=43992090

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2010/056684 WO2011060349A1 (fr) 2009-11-13 2010-11-15 Procédés de modulation de cellules souches mésenchymateuses

Country Status (1)

Country Link
WO (1) WO2011060349A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3969033A4 (fr) * 2019-05-17 2023-06-14 The Regents of the University of California Peptides modifiés par mps et leur utilisation
WO2023212443A1 (fr) * 2022-04-25 2023-11-02 Biomarck Pharmaceuticals, Ltd. Peptides et leurs procédés d'utilisation dans le traitement de maladies de la peau

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090203620A1 (en) * 2006-07-26 2009-08-13 Indu Parikh Methods for attenuating release of inflammatory mediators and peptides useful therein

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090203620A1 (en) * 2006-07-26 2009-08-13 Indu Parikh Methods for attenuating release of inflammatory mediators and peptides useful therein

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DEUEL ET AL.: "Chemotaxis of monocytes and neutrophils to platelet-derived growth factor.", J. CLIN. INVEST., vol. 69, no. 4, 1982, pages 1046 - 1049 *
MISHIMA ET AL.: "Chemotaxis of human articular chondrocytes and mesenchymal stem cells.", J. ORTHOP. RES., vol. 26, no. 10, 2008, pages 1407 - 1412 *
TAKASHI ET AL.: "A peptide against the N-terminus of myristoylated alanine-rich C kinase substrate inhibits degranulation of human leukocytes in vitro.", AM. J. RESPIR. CELL. MOL. BIOL., vol. 34, no. 6, 2006, pages 647 - 652 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3969033A4 (fr) * 2019-05-17 2023-06-14 The Regents of the University of California Peptides modifiés par mps et leur utilisation
WO2023212443A1 (fr) * 2022-04-25 2023-11-02 Biomarck Pharmaceuticals, Ltd. Peptides et leurs procédés d'utilisation dans le traitement de maladies de la peau

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