Placental derived stem cells and uses thereof

• US 20030235563A1
• Filed: 04/21/2003
• Published: 12/25/2003
• Est. Priority Date: 04/19/2002
• Status: Abandoned Application

• Current Assignee: University Of Pittsburgh (University of Pittsburgh of The Commonwealth System of Higher Education)
• Original Assignee: University Of Pittsburgh (University of Pittsburgh of The Commonwealth System of Higher Education)
• Inventors: Miki, Toshio, Strom, Stephen C.
• Application Number:
  US10/420,656
• Publication Number:
  US 20030235563A1
• 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: 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 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 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C12N 2500/25 Insulin-transferrin; Insulin-transferrin-selenium
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/115 Basic fibroblast growth factor (bFGF, FGF-2)
• CPC Class Codes: C12N 2501/119 Other fibroblast growth factors, e.g. FGF-4, FGF-8, FGF-10
• CPC Class Codes: C12N 2501/12 Hepatocyte growth factor [HGF]
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2503/02 Drug screening
• CPC Class Codes: C12N 2506/02 from embryonic cells
• CPC Class Codes: C12N 5/0605 Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly
• CPC Class Codes: C12N 5/067 Hepatocytes
• CPC Class Codes: C12N 5/0676 Pancreatic cells
• CPC Class Codes: C12N 5/069 Vascular Endothelial cells

Abstract

The present invention features novel placental derived stem cells and provides methods and compositions for the therapeutic uses of placental derived stem cells or placental derived stem cells that have been induced to differentiate into a desired tissue type into a recipient host in amounts sufficient to result in production of the desired cell type, i.e., hepatic, pancreatic, neuronal, or nervous tissue.

Claims

1. A composition comprising a placental derived stem cell, wherein the cell expresses at least one marker selected from the group:

c-kit, Thy-1, OCT-4, SOX2, hTERT, SSEA1, SSEA3, SSEA4, TRA1-60 and TRA1-81.

2. The composition of claim 1, which is deposited under ATCC Accession No. XXXX

3. A pharmaceutical composition of claim 1, wherein said stem cell is genetically engineered to produce a therapeutic protein in an amount effective to treat a subject.

4. A pharmaceutical composition comprising the composition of claim 1 in an amount effective to treat a subject with a liver disease, a vascular disease, a disease of nervous tissue, or a pancreatic disease.

5. A method wherein the stem cell of claim 1 is cultured in a dexamethasone, EGF, or TGF-alpha containing media under appropriate conditions and for a sufficient period of time to induce hepatocyte differentiation.

6. A hepatocyte obtained from the process of claim 5 wherein the cell expresses at least one marker selected from the group:

albumin, CYP3A4, A1AT, HNF1, HNF4 and C/EBP-alpha.

7. A pharmaceutical composition comprising the hepatocytes obtained from the process of claim 5 in an amount effective to treat a subject with a liver disease.

8. The hepatocytes obtained from the process of claim 5 wherein said hepatocytes are used in determining whether a test agent is toxic to a hepatic cell, comprising contacting said hepatocytes with the test agent for a time sufficient for a toxic effect on the cell to be detected, and determining the toxic effect on the hepatocytes.

9. The hepatocytes obtained from the process of claim 5 wherein said hepatocytes are used in determining a metabolic product of a test agent, comprising contacting said hepatocytes with the test agent for a time sufficient for the test agent to be metabolized, and detecting the presence of a metabolized product.

10. A method wherein the stem cells of claim 1 are cultured on matrigel under appropriate conditions and for a sufficient period of time to induce vascular endothelial cell differentiation.

11. A pharmaceutical composition comprising the vascular endothelial cells obtained from the process of claim 10 in an amount effective to treat a subject with a vascular disease.

12. The vascular endothelial cells obtained from the process of claim 10 wherein said vascular endothelial cells are used in determining whether a test agent is toxic to a vascular endothelial cell, comprising contacting said vascular endothelial cells with the test agent for a time sufficient for a toxic effect on the cells to be detected, and determining the toxic effect on the vascular endothelial cells.

13. The vascular endothelial cells obtained from the process of claim 10 wherein said vascular endothelial cells are used in determining a metabolic product of a test agent, comprising contacting said vascular endothelial cells with the test agent for a time sufficient for the test agent to be metabolized, and detecting the presence of a metabolized product.

14. A method wherein the stem cells of claim 1 are cultured in a dexamethasone, ITS and matrigel containing media under appropriate conditions and for a sufficient period of time to induce pancreatic cell differentiation.

15. A pancreatic cell obtained from the process of claim 14 wherein the cell expresses at least one marker selected from the group, Pax6, Pdx1 and insulin.

16. A pharmaceutical composition comprising the pancreatic cells obtained from the process of claim 14 in an amount effective to treat a subject with a pancreatic disease.

17. The pancreatic cells obtained from the process of claim 14 wherein said pancreatic cells are used in determining whether a test agent is toxic to a pancreatic cell, comprising contacting said pancreatic cells with the test agent for a time sufficient for a toxic effect on the cells to be detected, and determining the toxic effect on the pancreatic cells.

18. The pancreatic cells obtained from the process of claim 14 wherein said pancreatic cells are used in determining a metabolic product of a test agent, comprising contacting said pancreatic cells with the test agent for a time sufficient for the test agent to be metabolized, and detecting the presence of a metabolized product.

19. A method wherein the stem cells of claim 1 are cultured in a FGF-4 containing media under appropriate conditions and for a sufficient period of time to induce differentiation into cells of the nervous tissue.

20. A nervous tissue cell obtained from the process of claim 19, wherein the cell expresses at least one marker from the group:

GFAP,FLT1, CNP, and beta-tubulin III.

21. A pharmaceutical composition comprising the nervous tissue cells obtained from the process of claim 19 in an amount effective to treat a subject with a disease of the nervous tissue.

22. The nervous tissue cells obtained from the process of claim 19 wherein said nervous tissue cells are used in determining whether a test agent is toxic to a nervous tissue cell, comprising contacting said nervous tissue cells with the test agent for a time sufficient for a toxic effect on the cells to be detected, and determining the toxic effect on the nervous tissue cells.

23. The nervous tissue cells obtained from the process of claim 19 wherein said nervous tissue cells are used in determining a metabolic product of a test agent, comprising contacting said nervous tissue cells with the test agent for a time sufficient for the test agent to be metabolized, and detecting the presence of a metabolized product.

24. A process deriving a humanized organ comprising transplantation of placental-derived stem cells into an animal organ, wherein said stem cells regenerate and repopulate the animal organ to produce a humanized organ.

25. A humanized organ obtained from the process of claim 24.