Method for generating primate trophoblasts

• US 10,435,666 B2
• Filed: 06/02/2008
• Issued: 10/08/2019
• Est. Priority Date: 03/15/2002
• Status: Active Grant

• Current Assignee: WiCell Research Institute, Inc.
• Original Assignee: WiCell Research Institute, Inc.
• Inventors: Xu, Ren-He, Thomson, James A.
• Primary Examiner(s): Ton, Thaian N
• Assistant Examiner(s): Montanari, David A.
• Application Number:
  US12/131,610
• Publication Number:
  US 20150267165A1
• Time in Patent Office: 4,145 Days
• 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. An in vitro culture comprising a substantially pure, replenishable population of synchronous primate trophoblast cells, wherein the synchronous primate trophoblast cells express chorionic gonadotropin, are predominantly chorionic gonadotropin-beta (CG-β

) positive, and are derived directly in vitro from undifferentiated primate embryonic stem cells exposed to a 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) without passing through an embryoid body stage.

2. An in vitro culture comprising a substantially pure, replenishable population of synchronous, mononuclear primate trophoblast cells, wherein the synchronous, mononuclear primate trophoblast cells express chorionic gonadotropin, are predominantly chorionic gonadotropin-beta (CG-β

) positive, and are derived directly in vitro from undifferentiated primate embryonic stem cells exposed to a 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) without passing through an embryoid body stage.