REGENERATION AND REPAIR OF NEURAL TISSUE USING POSTPARTUM-DERIVED CELLS

• US 20140154226A1
• Filed: 01/10/2014
• Published: 06/05/2014
• 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
• Granted Patent: US 9,572,840 B2
• Time in Patent Office: Days
• US Class Current: 424/93.21
• 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 35/51 Umbilical cord; Umbilical cord blood; Umbilical stem cells
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2430/32 for nerve reconstruction
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• 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 5/0607 : 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 a neurodegenerative condition, the method comprising administering to the patient one or more cells in an amount effective to treat the neurodegenerative condition, 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 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 one or more of 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 at least one of a gene encoding;

interleukin 8;

reticulon 1;

chemokine (C-X-C motif) ligand 1 (melonoma 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 at least one 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 (supravalvular aortic stenosis, Williams-Beuren syndrome);

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 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 homeo box 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;

cytochrome c oxidase 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 neurodegenerative condition is a chronic or progressive neurodegenerative condition.

8. The method of claim 7, wherein the chronic or progressive neurodegenerative condition is Huntington'"'"'s disease, amyotrophic lateral sclerosis, tumor, multiple sclerosis or chronic peripheral nerve injury.

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

10. The method of claim 1, wherein the cells are genetically engineered to produce a gene product that promotes treatment of the neurodegenerative condition.

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

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

13. A pharmaceutical composition for treating a patient having a neurodegenerative condition, comprising a pharmaceutically acceptable carrier and one or more cells in an amount effective to treat the neurodegenerative condition, wherein said cells are isolated from human umbilical cord tissue substantially free of blood, or are generated by culturing 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 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 CD117.

14. The pharmaceutical composition of claim 13 wherein said cells produce each of CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2 and HLA-A, B, C.

15. The pharmaceutical composition of claim 14 wherein said cells lack the production of each of CD31, CD34, CD45, CD80, CD86, CD141, CD178, B7-H2, HLA-G, and HLA-DR, DP, DQ.

16. The pharmaceutical composition of claim 13, wherein the cells are induced in vitro to differentiate into a neural lineage cells prior to formulation of the composition.

17. The pharmaceutical composition of claim 13, wherein the cells are genetically engineered to produce a gene product that promotes treatment of the neurodegenerative condition.

18. The pharmaceutical composition of claim 13, comprising at least one other agent selected from the group consisting of an anti-inflammatory agent, and anti-apoptotic agent, an antioxidant and a growth factor.

19. A kit for treating a patient having a neurodegenerative condition, the kit comprising the pharmaceutical composition of claim 13 and instructions for using the kit in a method of treating the patient.

20. A method of treating a patient having a neurodegenerative condition, the method comprising administering to the patient, in an amount effective to treat the neurodegenerative condition, a composition comprising an extracellular matrix, conditioned medium or cell lysate of cells isolated from human umbilical cord tissue substantially free of blood, or generated by culturing 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 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 CD117.

21. A pharmaceutical composition for treating a patient having a neurodegenerative condition, which comprises a pharmaceutically acceptable carrier and a component selected from a conditioned medium, extracellular matrix or cell lysate of cells isolated from human umbilical cord tissue substantially free of blood, or generated by culturing 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 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 CD117.

22. A kit for treating a patient having a neurodegenerative condition, which comprises the pharmaceutical composition of claim 21;

and instructions for using the kit components for treatment of the neurodegenerative condition.