Neurogenesis from hepatic stem cells

• US 20040063202A1
• Filed: 08/28/2003
• Published: 04/01/2004
• Est. Priority Date: 08/28/2002
• Status: Abandoned Application

• Current Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Original Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Inventors: Deng, Jie, Petersen, Bryon E.
• Application Number:
  US10/651,829
• Publication Number:
  US 20040063202A1
• Time in Patent Office: Days
• US Class Current: 435/368
• 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 25/00 Drugs for disorders of the nervous system
• 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: C12N 2501/01 Modulators of cAMP or cGMP, e.g. non-hydrolysable analogs, phosphodiesterase inhibitors, cholera toxin
• CPC Class Codes: C12N 2506/14 from hepatocytes
• CPC Class Codes: C12N 5/0619 Neurons

Abstract

In vitro and in vivo approaches were used to induce hepatic oval cells to differentiate into cells expressing a neural cell-specific marker and displaying a neural morphology. Increasing cAMP in hepatic oval cells or co-culturing hepatic oval cells with neurospheres caused the hepatic oval cells to develop into cells displaying a neural cell-like phenotype. Hepatic oval cells transplanted into a brain differentiated into cells that phenotypically resembled all of the major cell types in the brain, including astrocytes, neurons, and microglia.

Claims

1. A method for producing a cell that expresses a neural cell phenotype, the method comprising the steps of:

(a) providing an hepatic oval cell; and

(b) placing the hepatic oval cell under conditions that promote the differentiation of the hepatic oval cell into a cell that expresses a neural cell phenotype.

2. The method of claim 1, wherein the neural cell phenotype comprises expression of marker selected from the group consisting of:

NFM, nestin, MAP2, β

III tubulin, α

-internexin, GFAP, S100, and CD11b.

3. The method of claim 1, wherein step (b) comprises contacting the hepatic oval cell with an agent increases cAMP concentration in the hepatic oval cell.

4. The method of claim 3, wherein the agent is an analogue of cAMP.

5. The analogue of claim 4, wherein the analogue is dibutyryl cAMP.

6. The method of claim 3, wherein the agent is an inhibitor of cAMP phosphodiesterase.

7. The method of claim 6, wherein the agent is 3-isobutyl-1-methylxanthine.

8. The method of claim 1, wherein step (b) comprises culturing the hepatic oval cell with a neurosphere.

9. The method of claim 1, wherein step (b) comprises transplanting the hepatic oval into a central nervous system tissue in an animal.

10. The method of claim 9, wherein the central nervous system tissue is a brain.

11. A cell that expresses a neural cell phenotype, the cell being made according to the method of claim 1.

12. The cell of claim 11, wherein the cell expresses are marker selected from the group consisting of:

NFM, nestin, MAP2, β

III tubulin, α

-internexin, GFAP, S100, and CD11b.

13. The cell of claim 11, wherein the marker is NFM.

14. The cell of claim 1, wherein the marker is nestin.

15. The cell of claim 11, wherein the marker is MAP2.

16. The cell of claim 11, wherein the marker is β

III tubulin.

17. The cell of claim 11, wherein the marker is α

-internexin.

18. The cell of claim 11, wherein the marker is GFAP.

19. The cell of claim 11, wherein the marker is S100.

20. The cell of claim 11, wherein the marker is CD11b.

21. A method of introducing a cell into a host animal subject, the method comprising the steps of:

(a) providing the animal subject; and

(b) introducing into the subject a cell made according to the method of claim 1.