Self-renewing pluripotent hepatic stem cells

• US 20030186439A1
• Filed: 03/06/2002
• Published: 10/02/2003
• Est. Priority Date: 03/06/2002
• Status: Active Grant

• Current Assignee: ReproCELL Inc.
• Original Assignee: ReproCELL Inc.
• Inventors: Nakauchi, Hiromitsu, Taniguchi, Hideki, Suzuki, Atsushi, Fukao, Katashi
• Granted Patent: US 7,150,990 B2
• Time in Patent Office: Days
• US Class Current: 435/370
• 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: C12N 2506/02 from embryonic cells
• CPC Class Codes: C12N 2506/14 from hepatocytes
• CPC Class Codes: C12N 5/0672 Stem cells; Progenitor cells; Precursor cells; Oval cells
• CPC Class Codes: C12N 5/0676 Pancreatic cells
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides clonal pluripotent hepatic stem cells using flow cytometry and in vitro single-cell-based assays. These cells possess multilineage differentiation potential and self-renewing capability; These cells could be clonally propagated in culture, where they continuously produced hepatocytes and cholanglocytes as descendants while maintaining primitive stem cells. When cells that expanded In vitro were transplanted into recipient animals, they morphologically and functionally differentiated into hepatocytes and cholanglocytes, with reconstitution of hepatocyte and bile duct structures. Furthermore, these cells differentiated into pancreatic ductal and acinar cells or intestinal epithelial cells when transplanted into pancreas or duodenal wall. These data indicate that self-renewing multipotent stem cells persist in the developing mouse liver and that such cells can be Induced to become cells of other organs of endodermal origin under appropriate microenvironment. Manipulation of hepatic stem cells may provide new insight into therapies for diseases of the digestive system.

Claims

1. A cloned, self-renewing pluripotent hepatic stem cell, or progeny thereof.

2. The stem cell according to claim 1 which is from primate.

3. The stem cell according to claim 1 which Is human.

4. The stem cell according to claim 1 which are capable of differentiating into hepatocytes or cholangiocytes.

5. The stem cell according to claim 1 which are capable of differentiating into pancreatic ductal, cinar or intestinal epithelial cells.

6. A purified composition essentially consisting of cloned, self-renewing pluripotent hepatic stem cells.

7. A method for producing a cloned, self-renewing pluripotent stem cells, comprising:

providing cells; and

fractionating said cells by selecting cells expressing c-Met⁺ CD49f^+/low.

8. The method according to claim 7, said step of fractionating further comprising selecting cells expressing c-Kit⁻

CD45⁻

TER119⁻

.

9. The method according to claim 7, wherein said cell is a liver cell.

10. The method according to claim 7, said cell is fetal.

11. A differentiated cell derived from a cloned, self-renewing pluripotent hepatic stem cell, or progeny thereof.

12. The differentiated cell according to claim 11, which is selected from the group consisting of a hepatocyte, a cholangiocyte, a pancreatic ductal cell, an acinar cell, and an intestinal epithelial cell.

13. A tissue regenerated from a cloned, self -renewing pluripotent hepatic stem cell., or progeny thereof.

14. The tissue according to claim 13 which is a liver tissue.

15. An organ regenerated from a cloned, self-renewing pluripotent hepatic stem cell, or progeny thereof.

16. The organ according to claim 15 which is a liver.

17. A method of transplanting cells into a recipient host. comprising:

obtaining a cloned, self-renewing pluripotent hepatic stem cell, or progeny thereof; and

transplanting said stem cell into the host.

18. A method of transplanting a tissue into a recipient host, comprising:

obtaining a cloned, self-renewing pluripotent hepatic stem cell, or progeny thereof;

regenerating a tissue from the stem cell; and

transplanting said tissue into the host.

19. The method according to claim 18, wherein said tissue is a liver tissue.

20. A method of transplanting an organ into a recipient host, comprising:

obtaining a cloned, self-renewing pluripotent hepatic stem cell, or progeny thereof;

regenerating an organ from the stem cell; and

transplanting said organ into the host.

21. The method according to claim 20, wherein said organ is a liver.