Postpartum cells derived from umbilical cord tissue, and methods of making and using the same

• US 8,318,483 B2
• Filed: 07/06/2006
• Issued: 11/27/2012
• Est. Priority Date: 06/27/2003
• Status: Active Grant

• Current Assignee: DePuy Synthes Products LLC (Johnson & Johnson)
• Original Assignee: Advanced Technologies and Regenerative Medicine, LLC
• Inventors: Mistry, Sanjay, Kihm, Anthony J., Harris, Ian Ross, Harmon, Alexander M., Messina, Darin J., Seyda, Agnieszka, Gosiewska, Anna
• Primary Examiner(s): DRISCOLL, LORA E BARNHART
• Application Number:
  US11/481,456
• Publication Number:
  US 20070036767A1
• Time in Patent Office: 2,336 Days
• Field of Search: None
• US Class Current: 435/325
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/50 Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
• CPC Class Codes: A61K 35/51 Umbilical cord; Umbilical cord blood; Umbilical stem cells
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 38/1808 Epidermal growth factor [EGF] urogastrone
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/1833 Hepatocyte growth factor; Scatter factor; Tumor cytotoxic factor II
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 38/1858 Platelet-derived growth factor [PDGF]
• CPC Class Codes: A61K 38/1866 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: A61K 38/1891 Angiogenesic factors; Angiogenin
• CPC Class Codes: A61K 38/19 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 38/204 IL-6
• CPC Class Codes: A61K 38/2053 IL-8
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 13/12 : of the kidneys
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/00 : Drugs for skeletal disorders
• CPC Class Codes: A61P 19/04 : for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/08 : for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 : for osteoporosis
• CPC Class Codes: A61P 21/00 : Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 : for peripheral neuropathies
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/06 : Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/06 : Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 2500/32 : Amino acids
• CPC Class Codes: C12N 2500/34 : Sugars
• CPC Class Codes: C12N 2500/44 : Thiols, e.g. mercaptoethanol
• CPC Class Codes: C12N 2500/90 : Serum-free medium, which may still contain naturally-sourced components
• CPC Class Codes: C12N 2500/95 : Protein-free medium and culture conditions
• CPC Class Codes: C12N 2501/12 : Hepatocyte growth factor [HGF]
• CPC Class Codes: C12N 2501/21 : Chemokines, e.g. MIP-1, MIP-2, RANTES, MCP, PF-4
• CPC Class Codes: C12N 2501/23 : Interleukins [IL]
• CPC Class Codes: C12N 2502/02 : embryonic cells
• CPC Class Codes: C12N 2506/02 : from embryonic cells
• CPC Class Codes: C12N 2506/03 : from non-embryonic pluripotent stem cells
• CPC Class Codes: C12N 2509/00 : Methods for the dissociation of cells, e.g. specific use of enzymes
• CPC Class Codes: C12N 2533/50 : Proteins
• CPC Class Codes: C12N 5/0605 : Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
• CPC Class Codes: C12N 5/0606 : Pluripotent embryonic cells, e.g. embryonic stem cells [ES] embryonic germ cells C12N5/0611, induced pluripotent stem cells C12N5/0696
• CPC Class Codes: C12N 5/0607 : Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696

Abstract

Cells derived from human umbilical cords are disclosed along with methods for their therapeutic use. Isolation techniques, culture methods and detailed characterization of the cells with respect to their cell surface markers, gene expression, and their secretion of trophic factors are described.

Claims

1. A homogeneous population of cells isolated from umbilicus tissue substantially free of blood wherein said homogeneous population of cells expresses CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, and HLA-A,B,C, and does not express CD31, CD34, CD 45, CD117, CD141, and HLA-DR,DP,DQ.

2. The isolated cell population of claim 1, wherein the cell population expresses a gene for one or more of interleukin 8;

reticulon 1;

chemokine (C-X-C motif) ligand 1;

chemokine (C-X-C motif) ligand 6;

chemokine (C-X-C motif) ligand 3;

or tumor necrosis factor-alpha-induced protein 3.

3. The isolated cell population of claim 1, wherein the cell population expresses a gene for each of interleukin 8;

reticulon 1;

chemokine (C-X-C motif) ligand 1;

chemokine (C-X-C motif) ligand 6;

chemokine (C-X-C motif) ligand 3; and

tumor necrosis factor-alpha-induced protein 3.

4. The isolated cell population of claim 3 wherein the expression is increased relative to that of a human cell which is a fibroblast, a mesenchymal stem cell or an iliac crest bone marrow cell.

5. The isolated cell population of claim 1, which relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell, has reduced expression of one or more genes selected from the group consisting of:

short stature homeobox 2;

heat shock 27 kDa protein 2;

chemokine (C-X-C motif) ligand 12;

elastin;

Homo sapiens mRNA;

cDNA DKFZp586M2022 (from clone DKFZp586M2022);

mesenchyme homeobox 2;

sine oculis homeobox homolog 1 (Drosophila);

crystallin, alpha B;

dishevelled associated activator of morphogenesis 2;

DKFZP586B2420 protein;

similar to neuralin 1;

tetranectin;

src homology three (SH3) and cysteine rich domain;

B-cell translocation gene 1, anti-proliferative;

cholesterol 25-hydroxylase;

runt-related transcription factor 3;

hypothetical protein FLJ23191;

interleukin 11 receptor-alpha;

procollagen C-endopeptidase enhancer;

frizzled homolog 7 (Drosophila);

hypothetical gene BC008967;

collagen type VIII, alpha 1;

tenascin C (hexabrachion);

iroquois homeobox protein 5;

hephaestin;

integrin beta 8;

synaptic vesicle glycoprotein 2;

Homo sapiens cDNA FLJ12280 fis, clone MAMMA1001744;

cytokine receptor-like factor 1;

potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4;

integrin alpha 7;

DKFZP586L151 protein;

transcriptional co-activator with PDZ-binding motif;

sine oculis homeobox homolog 2 (Drosophila);

KIAA1034 protein;

early growth response 3;

distal-less homeobox 5;

hypothetical protein FLJ20373;

aldo-keto reductase family 1, member C3;

biglycan;

fibronectin 1;

proenkephalin;

integrin beta-like 1 (with EGF-like repeat domains);

Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1968422;

EphA3;

KIAA0367 protein;

natriuretic peptide receptor C/guanylate cyclase C;

hypothetical protein FLJ14054;

Homo sapiens mRNA;

cDNA DKFZp564B222 (from clone DKFZp564B222);

vesicle-associated membrane protein 5;

EGF-containing fibulin-like extracellular matrix protein 1;

BCL2/adenovirus EIB 19 kpa interacting protein 3-like;

AE binding protein 1;

cytochrome c oxidase subunit VIIa polypeptide;

neuroblastoma suppression of tumorigenicity 1; and

insulin-like growth factor binding protein 2, 36 kDa.

6. The isolated cell population of claim 5, wherein the cell population expresses a gene for one or more of interleukin 8;

reticulon 1;

chemokine (C-X-C motif) ligand;

chemokine (C-X-C motif) ligand 6;

chemokine (C-X-C motif) ligand 3;

or tumor necrosis factor alpha-induced protein 3, wherein the expression is increased relative to that of a human cell which is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell.

7. The isolated cell population of claim 6, which relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell, has reduced expression of genes for each of:

short stature homeobox 2;

heat shock 27 kDa protein 2;

chemokine (C-X-C motif) ligand 12;

elastin;

Homo sapiens mRNA;

cDNA DKFZp586M2022 (from clone DKFZp586M2022);

mesenchyme homeobox 2;

sine oculis homeobox homolog 1 (Drosophila);

crystallin alpha B;

dishevelled associated activator of morphogenesis 2;

DKFZP586B2420 protein;

similar to neuralin 1;

tetranectin;

src homology three (SH3) and cysteine rich domain;

B-cell translocation gene 1 anti-proliferative;

cholesterol 25-hydroxylase;

runt-related transcription factor 3;

hypothetical protein FLJ23191;

interleukin 11 receptor alpha;

procollagen C-endopeptidase enhancer;

frizzled homolog 7 (Drosophila);

hypothetical gene BC008967;

collagen type VIII, alpha 1;

tenascin C (hexabrachion);

iroquois homeobox protein 5;

hephaestin;

integrin, beta 8;

synaptic vesicle glycoprotein 2;

Homo sapiens cDNA FLJ12280 fis, clone MAMMA1001744;

cytokine receptor-like factor 1;

potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4;

integrin, alpha 7;

DKFZP586L151 protein;

transcriptional co-activator with PDZ-binding motif (TAZ);

sine oculis homeobox homolog 2 (Drosophila);

KIAA1034 protein;

early growth response 3;

distal-less homeobox 5;

hypothetical protein FLJ20373;

aldo-keto reductase family 1 member C3;

biglycan;

fibronectin 1;

proenkephalin;

integrin beta-like 1;

Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1968422;

EphA3;

KIAA0367 protein;

natriuretic peptide receptor C/guanylate cyclase C;

hypothetical protein FLJ14054;

Homo sapiens mRNA;

cDNA DKFZp564B222 (from clone DKFZp564B222);

vesicle-associated membrane protein 5;

EGF-containing fibulin-like extracellular matrix protein 1;

BCL2/adenovirus E1B 19 kDa interacting protein 3-like;

AE binding protein 1;

cytochrome c oxidase subunit VIIa polypeptide 1;

neuroblastoma suppression of tumorigenicity 1; and

insulin-like growth factor binding protein 2, 36 kDa.

8. The isolated cell population of claim 7, wherein the cell population expresses a gene for each of interleukin 8;

reticulon 1;

chemokine (C-X-C motif) ligand;

chemokine (C-X-C motif) ligand 6;

chemokine (C-X-C motif) ligand 3; and

tumor necrosis factor alpha-induced protein 3, wherein the expression is increased relative to that of a human cell which is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell.

9. The isolated cell population of claim 1, wherein the cell population shows increased expression of a gene for each of interleukin 8;

reticulon 1; and

chemokine (C-X-C motif) ligand 3 relative to that of a human cell which is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell.