Regeneration and repair of neural tissue using postpartum-derived cells

• US 8,658,152 B2
• Filed: 09/06/2012
• Issued: 02/25/2014
• Est. Priority Date: 06/27/2003
• Status: Active Grant

• Current Assignee: DePuy Synthes Products LLC (Johnson & Johnson)
• Original Assignee: DePuy Synthes Products LLC (Johnson & Johnson)
• Inventors: Messina, Darin J., Harmon, Alexander M., Harris, Ian R., Kihm, Anthony J., Mistry, Sanjay, Seyda, Agnieszka, Yi, Chin-Feng, Gosiewska, Anna
• Primary Examiner(s): Gamett, Daniel C
• Application Number:
  US13/605,716
• Publication Number:
  US 20130022585A1
• Time in Patent Office: 537 Days
• Field of Search: None
• US Class Current: 424/93.1
• 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 postpartum umbilicus and placenta are disclosed. Pharmaceutical compositions, devices and methods for the regeneration or repair of neural tissue using the postpartum-derived cells are also disclosed.

Claims

1. A method of treating a patient having optic nerve damage, the method comprising administering to the patient one or more cells in an amount effective to treat the optic nerve damage, wherein said cells are isolated from human umbilical cord tissue substantially free of blood, or are generated from cultures of said isolated cells, wherein said cells are capable of self-renewal and expansion in culture and have the potential to differentiate into cells of at least a neural phenotype;

wherein said cells require L-valine for growth and can grow in at least about 5% oxygen;

wherein said cells exhibit the ability to undergo at least about 40 doublings in culture without a change in karyotype; and

wherein said cells lack production of CD 117.

2. The method of claim 1, wherein said cells produce each of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A, B, C.

3. The method of claim 1, wherein said cells lack the production of CD31, CD34, CD45, CD80, CD86, CD141, CD178, B7-H2, HLA-G and HLA-DR, DP, DQ.

4. The method of claim 1, wherein said cells secrete each of the factors MCP-1, IL-6, IL-8, GCP-2, HGF, KGF, FGF, HB-EGF, BDNF, TPO and TIMP1.

5. The method of claim 1, wherein said cells do not secrete the factors SDF-1 alpha, TGF-beta2, ANG2, PDGFbb and VEGF.

6. The method of claim 1, wherein said cells exhibit:

a) increased expression, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell, of a gene encoding;

interleukin 8;

reticulon 1;

chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha);

chemokine (C-X-C motif) ligand 6 (granulocyte chemotactic protein

     2);

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

tumor necrosis factor, alpha-induced protein 3; and

b) reduced expression, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell, of a gene encoding;

short stature homeobox 2;

heat shock 27 kDa protein 2;

chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor

     1);

elastin;

Homo sapiens mRNA;

cDNA DKFZp586M2022 (from clone DKFZp586M2022);

mesenchyme homeo box 2 (growth arrest-specific homeo box);

sine oculis homeobox homolog 1 (Drosophila);

crystallin, alpha B;

disheveled associated activator of morphogenesis 2;

DKFZP586B2420 protein;

similar to neuralin 1;

tetranectin (plasminogen binding protein);

src homology three (SH3) and cysteine rich domain;

cholesterol 25-hydroxylase;

runt-related transcription factor 3;

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;

neuroblastoma, suppression of tumorigenicity 1;

insulin-like growth factor binding protein 2, 36 kpa;

Homo sapiens cDNA F1112280 fis, clone MAMMA1001744;

cytokine receptor-like factor 1;

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

integrin, beta 7;

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

sine oculis homeobox homolog 2 (Drosophila);

KIAA1034 protein;

vesicle-associated membrane protein 5 (myobrevin);

EGF-containing fibulin-like extracellular matrix protein 1;

early growth response 3;

distal-less homeo box 5;

hypothetical protein F1120373;

aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II);

biglycan;

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

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 (atrionatriuretic peptide receptor C);

hypothetical protein F1114054;

Homo sapiens mRNA, cDNA DKFZp564B222 (from clone DKFZp564B222);

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

AE binding protein 1;

cytochrome coxidase subunit VIIa polypeptide 1 (muscle);

similar to neuralin 1;

B cell translocation gene 1;

hypothetical protein FLJ23191; and

DKFZp586L151.

7. The method of claim 1, wherein the cells are induced in vitro to differentiate into a neural lineage cells prior to administration.

8. The method of claim 1, wherein the cells are genetically engineered to produce a gene product that promotes treatment of the optic nerve damage.

9. The method of claim 1, wherein the cells are administered by injection or infusion.

10. The method of claim 1, wherein the cells are administered by implantation of a matrix or scaffold containing the cells.

11. The method of claim 1, wherein said cells produce each of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A, B, C and wherein said cells lack the production of CD31, CD34, CD45, CD80, CD86, CD141, CD178, B7-H2, HLA-G and HLA-DR, DP, DQ.