WO2013163539A1 - Cellules stromales issues d'un coeur foetal humain pour le traitement de patients à la suite d'un infarctus du myocarde - Google Patents

Cellules stromales issues d'un coeur foetal humain pour le traitement de patients à la suite d'un infarctus du myocarde Download PDF

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Publication number
WO2013163539A1
WO2013163539A1 PCT/US2013/038402 US2013038402W WO2013163539A1 WO 2013163539 A1 WO2013163539 A1 WO 2013163539A1 US 2013038402 W US2013038402 W US 2013038402W WO 2013163539 A1 WO2013163539 A1 WO 2013163539A1
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WIPO (PCT)
Prior art keywords
stromal cells
cells
fetal heart
treatment
cardiac
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PCT/US2013/038402
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English (en)
Inventor
Ian Mcniece
Original Assignee
The Cohen Mcniece Foundation
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.)
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Publication date
Application filed by The Cohen Mcniece Foundation filed Critical The Cohen Mcniece Foundation
Publication of WO2013163539A1 publication Critical patent/WO2013163539A1/fr

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    • 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
    • C12N5/0668—Mesenchymal stem cells from other natural sources
    • 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
    • A61K35/34—Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the invention relates generally to the field of cellular therapy for regenerative medicine, and particularly to the use of human fetal heart derived stromal cells for treatment of patients following myocardial infarction or for treatment of cardiac diseases.
  • MSCs are a key component of the microenvironment and have been shown to support hematopoietic stem cells.
  • the role of stromal cells in other tissues remains unclear.
  • Current clinical trials are evaluating the potential of MSCs in a number of tissues, including the heart, lungs and for vascular repair.
  • the BM is an ideal source of stromal cells (ie MSCs) however, it is unclear whether these cells will be capable of replacing the normal resident stromal population in non hematopoietic tissues.
  • stromal cells from fetal hearts which have a similar phenotype (Figure 1) to bone marrow derived MSCs, however, the gene expression patterns of growth factors and growth factor receptors differ between the two cell populations (Table 1).
  • cSTROMACell isolated stromal cells from fetal hearts
  • Figure 1 the gene expression patterns of growth factors and growth factor receptors differ between the two cell populations (Table 1).
  • Bone marrow cells were purchases from Allcells Inc (Emeryville, CA) who obtained the BM aspirates from normal donors under appropriate IRB approvals.
  • the MNC fraction was isolated by ficol separation and MSC were grown to confluency in T162 cm 2 tissue culture flasks (Corning, Action, MA) in alpha MEM plus 20% FCS.
  • Human fetal heart tissue was obtained with appropriate consent and IRB approval from aborted fetuses (15-22 weeks of gestation) from Advanced Biosciences Resources Inc. (Alameda, CA). The heart tissue was washed and dissected into small pieces and digested using collagenase IV (0.5% w/v; Invitrogen, Carlsbad, CA) for 5 minutes. The cell suspension was passed through a cell strainer and counted using Trypan Blue for viability. The cells were cultured in T 162 cm 2 tissue culture flasks in alpha MEM plus 20% FCS with twice weekly media exchange. Adherent cells developed within two weeks and were passaged using trypsin treatment when confluent.
  • Biotinylated cRNA was prepared using the Illumina TotalPrep RNA Amplification Kit (Ambion, Inc., Austin, TX) according to the manufacturer's instructions starting with 400 ng total RNA. Successful cRNA generation was checked using the Bioanalyzer 2100. Samples were added to the Beadchip after randomization using the randomized block design to reduce batch effects. Hybridization to the Sentrix Human-6 Expression BeadChip (Illumina, Inc., San Diego, CA), washing and scanning were performed according to the Illumina BeadStation 500 manual (revision C). The resulting microarray data was analyzed using Illumina Beadstudio software.
  • RNA quality was assessed with a Nanodrop 8000 Spectrophotometer (Thermo Scientific, Wilmington) and RNA integrity and presence of the small RNA fraction was determined using a Bioanalyzer 2100 (Agilent, Santa Clara). 60ng of total RNA was reverse transcribed using the human megaplex pool A and B primers and the Taqman miRNA reverse transcription kit (Applied Biosystems, Foster City) according to the manufacturer's instructions. Each sample was pre-amplified for 12 cycles using human pool A and B pre-amplification primers and the Taqman PreAmp Master Mix (Applied Biosystems) according to the manufacturer's instructions.
  • the pre-amplification reactions A and B were diluted and each reaction was combined with Taqman Gene-Expression Master Mix (Applied Biosystems) split in 8 aliquots and each aliquot added to one of the eight sample ports of the Human miRNA Taqman array A or B, respectively.
  • Each of the ports of the Taqman array feeds 48 reaction vessels holding individual miRNA assays.
  • Human miRNA Taqman array A and B hold 667 different miRNA target and 4 miRNA reference assays.
  • the real-time PCR reactions were run according to the manufacturer's instructions. RealTime Statminer Software (Integromics, Philadelphia) was used to analyze the data.
  • the reference miRNA assays included on the Taqman arrays did not pass the expression stability test. Therefore reference miRNA assays were chosen based on expression stability between different samples using the GeNorm algorithm.
  • the invention is directed to isolated fetal heart derived stromal cells, and preferably human isolated fetal heart derived stromal cells.
  • the invention is directed to a composition for treating cardiac tissue in a patient, the composition comprising isolated fetal heart derived stromal cells and a pharmaceutically acceptable carrier.
  • the stromal cells from fetal heart tissue are used in the treatment of cardiac diseases or myocardial damage or to enhance the regeneration of cardiac tissue.
  • the stromal cells from fetal heart tissue are used to treat a patient following a myocardial infarction.
  • the invention is preferably directed to a method of enhancing the regeneration of cardiac tissue in a patient comprising administering isolated fetal heart derived stromal cells to the cardiac tissue of a patient.
  • isolated fetal heart derived stromal cells are preferably in a composition further comprising a pharmaceutically acceptable carrier.
  • the cells are preferably administered following a myocardial infarction or for the treatment of a cardiac disease.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Developmental Biology & Embryology (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Cell Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Genetics & Genomics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Cardiology (AREA)
  • Wood Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Microbiology (AREA)
  • Vascular Medicine (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne des cellules stromales issues d'un coeur foetal humain pour le traitement de patients après un infarctus du myocarde, ou pour le traitement de maladies cardiaques. L'invention concerne des cellules stromales isolées à partir de coeur foetaux (cSTROMACell) qui ont un phénotype similaire à des MSC issues de moelle osseuse, toutefois, les profils d'expression de gènes de facteurs de croissance et de récepteurs de facteurs de croissance diffèrent entre les deux populations de cellules. Sur la base de l'origine de l'expression de cSTROMACell et de différents facteur de croissance, nous proposons que ces cellules sont plus efficaces pour la réparation cardiaque que des MSC issues moelle osseuse. Ces cellules présentent un plus grand potentiel pour s'intégrer dans le tissu cardiaque et pour stimuler la différenciation de cellules souches cardiaques résidentes en cardiomyocytes, ce qui entraîne une amélioration de la régénération de tissu cardiaque. En outre, elles partagent les propriétés immunosuppressives des MSC issues de la moelle osseuse, ce qui permet d'utiliser des MSC issues de cellules allogéniques sans rejet de greffe, et de supprimer l'inflammation.
PCT/US2013/038402 2012-04-26 2013-04-26 Cellules stromales issues d'un coeur foetal humain pour le traitement de patients à la suite d'un infarctus du myocarde WO2013163539A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261638921P 2012-04-26 2012-04-26
US61/638,921 2012-04-26

Publications (1)

Publication Number Publication Date
WO2013163539A1 true WO2013163539A1 (fr) 2013-10-31

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PCT/US2013/038402 WO2013163539A1 (fr) 2012-04-26 2013-04-26 Cellules stromales issues d'un coeur foetal humain pour le traitement de patients à la suite d'un infarctus du myocarde

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WO (1) WO2013163539A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110195054A1 (en) * 2009-10-06 2011-08-11 Michael Cohen Preparation And Use Of Stromal Cells For Treatment Of Cardiac Diseases
WO2012027740A1 (fr) * 2010-08-27 2012-03-01 University Of Miami Cellules précurseur cd271 issues de la moelle osseuse pour une réparation cardiaque

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110195054A1 (en) * 2009-10-06 2011-08-11 Michael Cohen Preparation And Use Of Stromal Cells For Treatment Of Cardiac Diseases
WO2012027740A1 (fr) * 2010-08-27 2012-03-01 University Of Miami Cellules précurseur cd271 issues de la moelle osseuse pour une réparation cardiaque

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
LUO ET AL.: "The Immature Heart: The Roles of Bone Marrow Stromal Stem Cells in Growth and Myocardial Repair.", THE OPEN CARDIOVASCULAR MEDICINE JOUMAL, vol. 1, 2007, pages 27 - 33 *
MCNIECE ET AL.: "The Role of Microenvironment Stromal Cells in Regenerative Medicine.", STEM CELL AND REGENERATIVE MEDICINE., 2010, pages 23 - 28 *
OSKOUEI ET AL.: "Increased Potency of Cardiac Stem Cells Compared with Bone Marrow Mesenchymal Stem Cells in Cardiac Repair.", STEM CELLS TRANSLATIONAL MEDICINE, 7 February 2012 (2012-02-07), pages 116 - 124 *

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