Human trophoblast stem cells and uses thereof
Inventors
Lee, Jau-Nan • Lee, Tony Tung-Ying • Lee, Yuta
Assignees
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Publication Number
US-10983111-B2
Publication Date
2021-04-20
Expiration Date
Abstract
Disclosed herein are human trophoblast stem (hTS) cells, differentiated cells thereof, derivatives thereof such as cellular mass, and uses thereof. The isolation of hTS cells can express FGF4, FGFR-2, Oct4, Thy-1, and stage-specific embryonic antigens distributed in different compartments of the cell. The 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 the hTS cells, Oct4 and fgfr-2 expressions can be knockdown by bFGF. The hTS cells could apply to human cell differentiation and for gene and cell-based therapies.
Core Innovation
The invention relates to isolating and using human trophoblast stem cells obtained from villous tissue of tubal ectopic pregnancy and maintaining their stem cell characteristics. The hTS cells are described as expressing trophoblast stem cell markers SSEA-1, SSEA-3, and SSEA-4, and expressing Oct4, FGFR2, and FGF4, while having normal karyotype and maintaining telomere length.
The invention also describes differentiation of the human trophoblast stem cells into derivatives of all three germ layers, including endodermal, mesodermal, and ectodermal derivatives. The document further describes embryoid bodies, neural differentiation, dopaminergic neurons, and pancreatic β-islet-like cells.
The document describes a gene-switch regulation approach for the hTS cells using bFGF-mediated knockdown of Oct4/FGFR2. It additionally discloses a collagen-embedded cellular system in which human trophoblast stem cells are embedded in collagen and form mesodermal and/or other germ-layer-associated cell compositions, including a cellular mass with differentiated pancreatic β-islet-like cells and insulin secretion.
Claims Coverage
The independent claims describe a collagen-based cellular mass containing human trophoblast stem cells, with four inventive feature variants across the claim set.
Collagen-embedded cellular mass with mesodermal cells
A cellular mass comprising collagen embedded with human trophoblast stem cells and further comprising a mesodermal cell.
Collagen-embedded cellular mass with pancreatic β-islet-like cells
A cellular mass comprising collagen embedded with human trophoblast stem cells and further comprising pancreatic β-islet like cells capable of developing to a pancreatic tissue or organ.
Acidic-solution collagen cellular mass with trophoblast stem cells
A cellular mass comprising collagen embedded with human trophoblast stem cells, wherein the collagen is in an acidic solution.
Umbrella-like layered trophoblast stem cells on collagen
A cellular mass comprising collagen embedded with human trophoblast stem cells, wherein at least some of the human trophoblast stem cells are present in a flat, umbrella-like layer on the collagen.
Overall, the claim set centers on collagen embedded with human trophoblast stem cells, with variants specifying mesodermal or pancreatic β-islet-like cells, collagen in an acidic solution, and a flat, umbrella-like layer morphology for at least some trophoblast stem cells.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Human cell differentiation and differentiation into derivatives of all three germ layers, including neural differentiation and pancreatic β-islet-like cells with insulin secretion.
Gene/cell therapy and therapeutic targeting, with examples including neurodegenerative disease and diabetes/cancer.
Therapeutic disease modeling involving Parkinson’s disease, including chimeric behavior in SCID mice and a Parkinsonism model (6-OHDA lesion model).
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