Human trophoblast stem cells and methods of therapeutic screening

• US 9,335,322 B2
• Filed: 06/04/2013
• Issued: 05/10/2016
• Est. Priority Date: 02/24/2005
• Status: Active Grant

• Current Assignee: Accelerated Biosciences Corp.
• Original Assignee: Accelerated Biosciences Corp.
• Inventors: Lee, Tony Tung-Ying, Lee, Jau-Nan, Lee, Yuta
• Primary Examiner(s): Kelly, Robert M
• Application Number:
  US13/909,469
• Publication Number:
  US 20130337458A1
• Time in Patent Office: 1,071 Days
• Field of Search: None
• US Class Current: 1/1
• 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 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61K 35/54 Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: C12N 2500/34 Sugars
• CPC Class Codes: C12N 2500/38 Vitamins
• CPC Class Codes: C12N 2500/44 Thiols, e.g. mercaptoethanol
• CPC Class Codes: C12N 2501/115 Basic fibroblast growth factor (bFGF, FGF-2)
• CPC Class Codes: C12N 2506/02 from embryonic cells
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• 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 5/0677 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells
• CPC Class Codes: G01N 33/5073 Stem cells

Abstract

Existence of human trophoblast stem (hTS) cells has been suspected but unproved. The isolation of hTS cells is reported in the early stage of chorionic villi by expressions of FGF4, FGFR-2, Oct4, Thy-1, and stage-specific embryonic antigens distributed in different compartments of the cell. hTS cells are able to derive into specific cell phenotypes of the three primitive embryonic layers, produce chimeric reactions in mice, and retain a normal karyotype and telomere length. In hTS cells, Oct4 and fgfr-2 expressions can be knockdown by bFGF. These facts suggest that differentiation of the hTS cells play an important role in implantation and placentation. hTS cells could be apply to human cell differentiation and for gene and cell-based therapies.

Claims

1. An in vitro method of screening for a therapeutic compound, comprising:

a. contacting a test substance in vitro with an isolated human trophoblast stem cell that expresses Octamer-4 (Oct4) and SSEA-4;

b. evaluating the isolated human trophoblast stem cell in vitro to determine if the test substance modulates differentiation or activity of the isolated human trophoblast stem cell; and

c. selecting the test substance as the therapeutic compound if the test substance modulates the differentiation or activity of the isolated human trophoblast stem cell.

2. The in vitro method of claim 1, wherein the therapeutic compound is an immunosuppressive agent or an immunosupportive agent.

3. The in vitro method of claim 1, wherein the therapeutic compound modulates bFGF, Oct4, FGFR-2, or FGF4.

4. The in vitro method of claim 3, wherein the therapeutic compound is an inhibitor of bFGF, Oct4, FGFR-2, or FGF4.

5. The in vitro method of claim 1, wherein the therapeutic compound is an antibody.