Postpartum-derived cells for use in treatment of disease of the heart and circulatory system

• US 20060188983A1
• Filed: 12/30/2005
• Published: 08/24/2006
• Est. Priority Date: 06/27/2003
• Status: Abandoned Application

• Current Assignee: DePuy Synthes Products LLC (Johnson & Johnson)
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Harmon, Alexander M., Messina, Darin J., Mistry, Sanjay, Gosiewska, Anna, Seyda, Agnieszka, Kihm, Anthony J., Harris, Ian Ross, Yi, Chin-Feng
• Application Number:
  US11/322,372
• Publication Number:
  US 20060188983A1
• Time in Patent Office: Days
• US Class Current: 435/366
• 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 tissue are disclosed along with methods for their therapeutic use in diseases of the heart or circulatory system are disclosed. Cells may be used therapeuticall in either differentiated or undifferentiated forms, in homogenous cultures, or as populations with other cells, and in conjunction with other bioactive factors.

Claims

1. An isolated postpartum-derived cell comprising an L-valine-requiring cell derived from human postpartum tissue substantially free of blood, said cell capable of self-renewal and expansion in culture and having the potential to differentiate into a cell of cardiomyocyte phenotypes;

the cell capable of growth in an atmosphere containing oxygen from about 5% to at least about 20%;

wherein said cell comprises at least one of the following characteristics;

potential for at least about 40 doublings in culture;

attachment and expansion on a coated or uncoated tissue culture vessel, wherein a coated tissue culture vessel comprises a coating of gelatin, laminin, collagen, polyornithine, vitronectin, or fibronectin;

production of at least one of tissue factor, vimentin, and alpha-smooth muscle actin;

production of at least one of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A,B,C;

lack of production of at least one of CD31, CD34, CD45, CD80, CD86, CD117, CD141, CD178, B7-H2, HLA-G, and HLA-DR,DP,DQ, as detected by flow cytometry;

expression of at least one of 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;

expression of at least one of C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 2 (activation-induced);

Wilms tumor 1;

aldehyde dehydrogenase 1 family, member A2; and

renin;

oxidized low density lipoprotein (lectin-like) receptor 1;

Homo sapiens, clone IMAGE;

4179671, mRNA, partial cds;

protein kinase C, zeta;

hypothetical protein DKFZp564FO13;

downregulated in ovarian cancer 1;

Homo sapiens mRNA; and

cDNA DKFZp547K1113 (from clone DKFZp547K1113);

expression, which relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an ileac crest bone marrow cell, is reduced for at least one of;

short stature homeobox 2;

heat shock 27 kDa protein 2;

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

     1);

elastin (supravalvular aortic stenosis, Williams-Beuren syndrome);

Homo sapiens mRNA;

cDNA DKFZp586M2022 (from clone DKFZp586M2022);

mesenchyme homeobox 2 (growth arrest-specific homeobox);

sine oculis homeobox homolog 1 (Drosophila);

crystallin, alpha B;

dishevelled associated activator of morphogenesis 2;

DKFZP586B2420 protein;

similar to neuralin 1;

tetranectin (plasminogen binding protein);

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 (3-alpha hydroxysteroid dehydrogenase, type II);

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 (atrionatriuretic peptide receptor C);

hypothetical protein FLJ 14054;

Homo sapiens mRNA;

cDNA DKFZp564B222 (from clone DKFZp564B222);

vesicle-associated membrane protein 5 (myobrevin);

EGF-containing fibulin-like extracellular matrix protein 1;

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

AE binding protein 1;

cytochrome c oxidase subunit VIIIa polypeptide 1 (muscle);

neuroblastoma, suppression of tumorigenicity 1;

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

secretion of at least one of MCP-1, IL-6, IL-8, GCP-2, HGF, KGF, FGF, HB-EGF, BDNF, TPO, MIP1a, RANTES, and TIMP1; and

lack of secretion of at least one of TGF-beta2, ANG2, PDGFbb, MIP1b, 1309, MDC, and VEGF, as detected by ELISA.

2. The postpartum-derived cell of claim 1 isolated in the presence of one or more enzyme activities comprising metalloprotease activity, mucolytic activity and neutral protease activity.

3. The postpartum-derived cell of claim 2 wherein the enzyme activities are collagenase and dispase.

4. The postpartum-derived cell of claim 3 further comprising hyaluronidase.

5. The postpartum-derived cell of claim 4 comprising a normal karyotype.

6. The postpartum-derived cell of claim 5 that maintains its karyotype as it is passaged.

7. The postpartum-derived cell of claim 6 wherein the cell expresses each of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, and HLA-A,B,C.

8. The postpartum-derived cell of claim 7 wherein the cell does not express any of CD31, CD34, CD45, CD1 17, CD141, or HLA-DR,DP,DQ, as detected by flow cytometry.

9. The postpartum-derived cell of claim 8 wherein the cell does not spontaneously differentiate along a cardiogenic, angiogenic, hemangiogenic, or vasculogenic pathway when cultured in Growth Medium.

10. A population of cells comprising the postpartum-derived cell of claim 8.

11. The population of claim 10 comprising from about 1% postpartum-derived cells to about 10% postpartum cells.

12. The population of claim 11 comprising about 50% postpartum-derived cells.

13. The population of claim 12 comprising at least 90% postpartum-derived cells.

14. The population of claim 13 comprising substantially only postpartum-derived cells.

15. The population of claim 14 comprising a clonal cell line of postpartum-derived cells.

16. A cell lysate prepared from the population of claim 10.

17. The population of claim 10 incubated in the presence of one or more factors which stimulate stem cell differentiation along a cardiogenic, angiogenic, hemangiogenic, or vasculogenic pathway.

18. The population of claim 17 wherein the factors comprise at least one of a demethylation agent, a member of BMP, FGF, TAK, GATA, Csx, NK, MEF2, ET-1, and Wnt factor families, Hedgehog, Csx/Nkx-2.5, and anti-Wnt factors.

19. The population of claim 18 wherein the demethylation agent comprises an inhibitor of DNA methyltransferase or an inhibitors of a histone deacetylase, or inhibitors of a repressor complex.

20. The population of claim 18 wherein the demethylation agents comprise at least one of 5-azacytidine, 5-aza-2′

-deoxycytidine, DMSO, chelerythrine chloride, retinoic acid or salts thereof, 2-amino-4-(ethylthio)butyric acid, procainamide, and procaine.

21. The population of claim 10 that is seed onto a matrix to form a matrix-cell complex.

22. The population of claim 21 wherein the matrix is a scaffold.

23. The population of claim 22 wherein the scaffold is bioabsorbable.

24. The population of claim 23 wherein the scaffold comprises at least one other cell type.

25. The population of claim 24 wherein the other cell type is a stem cell.

26. A therapeutic cell composition comprising a pharmaceutically-acceptable carrier and post-partum-derived cells derived from human postpartum tissue substantially free of blood, said cells capable of self-renewal and expansion in culture and having the potential to differentiate into cells of cardiomyocyte phenotypes;

the cells capable of growth in an atmosphere containing oxygen from about 5% to at least about 20%;

wherein said cells;

require L-valine for growth;

have the potential for at least about 40 doublings in culture;

attach and expand on a coated or uncoated tissue culture vessel, wherein a coated tissue culture vessel comprises a coating of gelatin, laminin, collagen, polyomithine, vitronectin, or fibronectin;

produce tissue factor, vimentin, and alpha-smooth muscle actin;

produce each of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, and HLA-A,B,C; and

do not produce any of CD31, CD34, CD45, CD117, CD141, or HLA-DR,DP,DQ, as detected by flow cytometry.

41. The therapeutic cell composition of claim 26 further comprising the following characteristics:

expression of at least one of 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;

expression of at least one of C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 2 (activation-induced);

Wilms tumor 1;

aldehyde dehydrogenase 1 family, member A2; and

renin;

oxidized low density lipoprotein (lectin-like) receptor 1;

Homo sapiens, clone IMAGE;

4179671, mRNA, partial cds;

protein kinase C, zeta;

hypothetical protein DKFZp564F013;

downregulated in ovarian cancer 1;

Homo sapiens mRNA; and

cDNA DKFZp547K1113 (from clone DKFZp547K1113);

expression, which relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an ileac crest bone marrow cell, is reduced for at least one of;

short stature homeobox 2;

heat shock 27 kDa protein 2;

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

     1);

elastin (supravalvular aortic stenosis, Williams-Beuren syndrome);

Homo sapiens mRNA;

cDNA DKFZp586M2022 (from clone DKFZp586M2022);

mesenchyme homeobox 2 (growth arrest-specific homeobox);

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 kDa;

Homo sapiens cDNA FLJ12280 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 homeobox 5;

-hypothetical protein FLJ20373;

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 FLJ14054;

Homo sapiens mRNA;

cDNA DKFZp564B222 (from clone DKFZp564B222);

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

AE binding protein 1; and

cytochrome c oxidase subunit VIla polypeptide 1 (muscle);

secretion of at least one of MCP-1, IL-6, IL-8, GCP-2, HGF, KGF, FGF, HB-EGF, BDNF, TPO, MIP1a, RANTES, and TIMP1; and

lack of secretion of at least one of TGF-beta2, ANG2, PDGFbb, MIP1b, 1309, MDC, and VEGF, as detected by ELISA.

42. The therapeutic cell composition of claim 41 comprising about 50% postpartum-derived cells.

43. The therapeutic cell composition of claim 42 comprising substantially only postpartum-derived cells.

44. The therapeutic cell composition of claim 43 comprising a substantially homogeneous population of postpartum-derived cells.

45. The therapeutic cell composition of claim 44 comprising a clonal cell line of postpartum-derived cells.

46. The therapeutic cell composition of claim 44 wherein the substantially homogeneous population is umbilical-derived cells.

47. The therapeutic cell composition of claim 44 wherein the substantially homogeneous population is substantially free of maternal cells.

48. The therapeutic cell composition of claim 44 wherein the substantially homogeneous population is placental-derived cells.

49. The therapeutic cell composition of claim 44 wherein the substantially homogeneous population is of neonatal origin.

50. The therapeutic cell composition of claim 44 wherein the substantially homogeneous population is of maternal origin.

27-40. -40. (canceled)

51-58. -58. (canceled)

59. A coculture of human postpartum cells and another mammalian cell, wherein at least one of the cells is a cardiomyoblast, angioblast, or hemangioblast or induced to differentiate along a pathway leading to a cardiomyoblast, angioblast or hemangioblast.

60-61. -61. (canceled)