Cartilage and bone repair and regeneration using postpartum-derived cells

• US 11,191,789 B2
• Filed: 06/25/2004
• Issued: 12/07/2021
• Est. Priority Date: 06/27/2003
• Status: Active Grant

• Current Assignee: Depuy Synthes Products Incorporated (Johnson & Johnson)
• Original Assignee: Depuy Synthes Products Incorporated (Johnson & Johnson)
• Inventors: Kihm, Anthony J., Seyda, Agnieszka, Dhanaraj, Sridevi, Wang, Ziwei, Harmon, Alexander M., Harris, Ian Ross, Messina, Darin J., Mistry, Sanjay, Gosiewska, Anna, Yi, Chin-Feng
• Primary Examiner(s): Wilson, Michael C
• Application Number:
  US10/876,998
• Publication Number:
  US 20050019865A1
• Time in Patent Office: 6,374 Days
• Field of Search: 435325, 435455, 424 931
• 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. A method of forming cartilage in a patient, said method comprising administering to said patient a matrix comprising a homogeneous population of undifferentiated umbilical cord tissue-derived cells, wherein the homogeneous population of cells is obtained from human postpartum umbilical cord substantially free of blood, and wherein said homogeneous population of cells:

i) exhibits increased expression, relative to a human cell that is a fibroblast, a mesenchymal stem cell, or an iliac crest bone marrow cell, of an endogenous gene encoding interleukin 8 and an endogenous gene encoding reticulon 1;

ii) secretes MCP-1, IL-6, IL-8, GCP-2, HGF, KGF, FGF, HB-EGF, BDNF, TPO, MIP1b, RANTES and TIMP 1;

iii) produces CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, and HLA-A, B, C; and

iv) lacks production of CD31, CD34, CD117, CD141, and HLA-DR, DP, DQ,

whereby cartilage is formed in the matrix.

2. The method of claim 1 wherein said matrix is implanted into said patient.

3. The method of claim 1 wherein said matrix comprises at least one bioactive factor.

4. The method of claim 1 wherein said matrix is administered to a bone of said patient.

5. The method of claim 1 wherein said matrix is administered to cartilage of said patient.

6. The method of claim 1 wherein said homogeneous cell population is capable of self-renewal and expansion in culture, has the potential to differentiate into cells of a chondrogenic phenotype, and requires L-valine for growth.

7. The method of claim 1 wherein said homogeneous cell population has the potential for at least 40 doublings in culture.

8. The method of claim 1 wherein said homogeneous cell population does not express any of CD80, CD86, CD178, or HLA-G.

9. The method of claim 1 wherein said homogeneous cell population expresses a gene for each of 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.

10. The method of claim 1 wherein said homogeneous cell population does not secrete any of the factors SDF-1alpha, TGF-beta2, ANG2, PDGFbb, MIP1a and VEGF.

11. The method of claim 1 wherein said homogeneous cell population is obtained by contacting umbilical cord tissue with an enzyme solution comprising a matrix metalloprotease, a neutral protease and a mucolytic enzyme.

12. A method of forming cartilage in a patient, said method comprising administering to said patient a matrix comprising a homogeneous population of undifferentiated umbilical cord tissue-derived cells, wherein said homogenous population of cells is deposited with ATCC under Accession No. PTA-6067, whereby cartilage is formed in the matrix.

14. The method of claim 12, wherein the homogeneous population of undifferentiated umbilical cord tissue-derived cells has the potential to differentiate into cells of a chondrogenic phenotype.

13. A method of forming cartilage in a patient, said method comprising administering to said patient a matrix comprising a homogeneous population of undifferentiated umbilical cord tissue-derived cells, wherein said homogenous population of cells is deposited with ATCC under Accession No. PTA-6068, whereby cartilage is formed in the matrix.

15. The method of claim 13, wherein the homogeneous population of undifferentiated umbilical cord tissue-derived cells has the potential to differentiate into cells of a chondrogenic phenotype.