Method for generating primate trophoblasts

• US 7,148,062 B2
• Filed: 03/14/2003
• Issued: 12/12/2006
• Est. Priority Date: 03/15/2002
• Status: Active Grant

• Current Assignee: WiCell Research Institute, Inc.
• Original Assignee: WiCell Research Institute, Inc.
• Inventors: Thomson, James A., Xu, Ren-He
• Primary Examiner(s): Nguyen, Dave Trong
• Assistant Examiner(s): Montanari, David A.
• Application Number:
  US10/389,484
• Publication Number:
  US 20040005701A1
• Time in Patent Office: 1,369 Days
• Field of Search: 435/325, 435/363, 435/366
• US Class Current: 435/325
• CPC Class Codes: C12N 2501/155 Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
• CPC Class Codes: C12N 2501/19 Growth and differentiation factors [GDF]
• 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

Abstract

The first method to cause a culture of human and other primate stem cells to directly and uniformly differentiate into a committed cell lineage is disclosed. Treatment of primate stem cells with a single protein trophoblast induction factor causes the cells to transform into human trophoblast cells, the precursor cells of the placenta. Several protein factors including bone morphogenic protein 4 (BMP4), BMP2, BMP7, and growth and differentiation factor 5 can serve as trophoblast-inducting factors.

Claims

1. A method to induce human embryonic stem cells to differentiate into human trophoblast cells comprising the step of culturing the human stem cells in a culture medium comprising presence of a protein trophoblast inducing factor selected from the group consisting of bone morphogenetic protein 4 (BMP4), bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 7 (BMP7), and growth and differentiation factor 5 (GDF5), to cause said stem cells to differentiate into human trophoblast cells.

2. The method of claim 1 wherein the factor concentration is between 1 and 100 nonograms per milliliter of the culture medium.

3. A method to induce primate embryonic stem cells to differentiate into primate trophoblast cells comprising the step of culturing the primate stem cells in a culture medium comprising presence of a protein trophoblast-inducing factor selected from the group consisting of bone morphogenic protein 4 (BMP4), bone morphogenic protein 2 (BMP2), bone morphogenic protein 7 (BMP7) and growth and differentiation factor 5 (GDF5).

4. The method of claim 3 wherein the factor concentration is between 1 and 100 nanograms per milliliter of the culture medium.