Cartilage and bone repair and regeneration using postpartum-derived cells

• US 20060154367A1
• Filed: 12/29/2005
• Published: 07/13/2006
• Est. Priority Date: 06/27/2003
• Status: Abandoned Application

• Current Assignee: Ethicon Incorporated (Johnson & Johnson)
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Wang, Ziwei, Harmon, Alexander M., Messina, Darin J., Mistry, Sanjay, Gosiewska, Anna, Seyda, Agnieszka, Kihm, Anthony J., Dhanaraj, Sridevi, Harris, Ian Ross
• Application Number:
  US11/322,003
• Publication Number:
  US 20060154367A1
• 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 and methods for their isolation and induction to differentiate to cells of a chondrogenic or osteogenic phenotype are provided by the invention. The invention further provides cultures and compositions of the postpartum-derived cells and products related thereto. The postpartum-derived cells of the invention and products related thereto have a plethora of uses, including but not limited to research, diagnostic, and therapeutic applications, for example, in the treatment of bone and cartilage conditions.

Claims

1-19. -19. (canceled)

20. A cell produced by a method comprising exposing a postpartum-derived cell (PPDC) to one or more osteogenic differentiation-inducing agents,

wherein said PPDC is derived from human postpartum tissue substantially free of blood, wherein said PPDC is capable of self-renewal and expansion in culture and has the potential to differentiate into a cell of an osteogenic or chondrogenic phenotype;

wherein said PPDC requires L-valine for growth;

wherein said PPDC is capable of growth in about 5% to about 20% oxygen;

wherein said PPDC further comprises at least one of the following characteristics;

(a) production of at least one of granulocyte chemotactic protein 2 (GCP-2), reticulon 1, tissue factor, vimentin, and alpha-smooth muscle actin;

(b) lack of production of at least one of GRO-alpha or oxidized low density lipoprotein receptor, as detected by flow cytometry;

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

(d) 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;

(e) expression, which relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an ileac crest bone marrow cell, is increased for 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 or expression, which relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an ileac crest bone marrow cell, is increased for at least one of C-type lectin superfamily member A2, Wilms tumor 1, aldehyde dehydrogenase 1 family member A2, renin, oxidized low density lipoprotein receptor 1, protein kinase C zeta, clone IMAGE;

4179671, hypothetical protein DKFZp564F013, downregulated in ovarian cancer 1, and clone DKFZp547K1113;

(f) 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;

cDNA DKFZp586M2022 (from clone DKFZp586M2022);

mesenchyme homeobox 2;

sine oculis homeobox homolog 1;

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;

hypothetical gene BC008967;

collagen, type VIII, alpha 1;

tenascin C;

iroquois homeobox protein 5;

hephaestin;

integrin, beta 8;

synaptic vesicle glycoprotein 2;

cDNA FLJ12280 fis, clone MAMMA1001744;

cytokine receptor-like factor 1;

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

integrin, alpha 7;

DKFZP586L151 protein;

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

sine oculis homeobox homolog 2;

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);

cDNA clone EUROIMAGE 1968422;

EphA3;

KIAA0367 protein;

natriuretic peptide receptor C/guanylate cyclase C (atrionatriuretic peptide receptor C);

hypothetical protein FLJ14054;

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 (muscle);

neuroblastoma, suppression of tumorigenicity 1; and

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

(g) secretion of at least one of monocyte chemotactic protein-1, interleukin(IL)-6, IL-8, granulocyte chemotactic protein-2, hepatocyte growth factor, keratinocyte growth factor, fibroblast growth factor, heparin binding-epidermal growth factor, brain derived neurotrophic factor, thrombopoietin, macrophage inflammatory protein (MIP-1a, RANTES, and tissue inhibitor of matrix metalloprotease 1;

(h) lack of secretion of at least one of transforming growth factor-beta2, angiopoetin-2, platelet derived growth factor-bb, MIP1b, I309, macrophage-derived chemokine, and vascular endothelial growth factor, as detected by ELISA; and

(i) the ability to undergo at least 40 population doublings in culture.

29. A cell population comprising the cell of claim 20.

30. The cell population of claim 29 wherein said cell population is substantially homogeneous.

31. The cell population of claim 29 wherein said cell population is heterogeneous.

32. The cell population of claim 31 further comprising at least one cell type of bone marrow cells, osteocytes, osteoblasts, osteoclasts, bone lining cells, stem cells or other pluripotent or multipotent cell.

37. A cell lysate prepared from the cell population of claim 29.

38. A soluble cell fraction prepared from the cell lysate of claim 37.

41. An extracellular matrix of the cell population of claim 29.

44. A composition comprising the cell population of claim 29 and one or more bioactive factors.

49. A pharmaceutical composition comprising a cell of claim 20 and a pharmaceutically acceptable carrier.

52. A pharmaceutical composition comprising the extracellular matrix of claim 41 and a pharmaceutically acceptable carrier.

55. A pharmaceutical composition comprising the lysate of claim 37 and a pharmaceutically acceptable carrier.

64. A matrix comprising a cell population of claim 29.

67. The matrix of claim 64 wherein said matrix comprises a three-dimensional scaffold.

99. The pharmaceutical composition of claim 49 wherein said composition comprises an effective amount of said cells to treat a bone or cartilage condition.

102. The pharmaceutical composition of claim 52 wherein said composition comprises an effective amount of said extracellular matrix to treat a bone or cartilage condition.

105. The pharmaceutical composition of claim 55 wherein said composition comprises an effective amount of said lysate to treat a bone or cartilage condition.

108. The pharmaceutical composition of claim 49 further comprising at least one other cell type of stem cells, bone marrow cells, chondrocytes, chondroblasts, osteocytes, osteoblasts, osteoclasts, bone lining cells, and other bone or cartilage progenitor cells.

21-28. -28. (canceled)

33-36. -36. (canceled)

39-40. -40. (canceled)

42-43. -43. (canceled)

45-48. -48. (canceled)

50-51. -51. (canceled)

53-54. -54. (canceled)

56-63. -63. (canceled)

65-66. -66. (canceled)

68-98. -98. (canceled)

100-101. -101. (canceled)

103-104. -104. (canceled)

106-107. -107. (canceled)