Human trophoblast stem cells and uses thereof

Inventors

Lee, Jau-Nan • Lee, Tony Tung-Ying • Lee, Yuta

Assignees

Accelerated Biosciences Corp

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 apply to human cell differentiation and for gene and cell-based therapies.

Core Innovation

The patent discloses human trophoblast stem (hTS) cells isolated from unruptured tubal ectopic pregnancy, specifically early villous trophoblast. The isolated hTS cells are characterized by expression of SSEA-1, SSEA-3, and SSEA-4, and by expression patterns including Oct4, FGFR2, and FGF4. The cells are further characterized as having a normal karyotype and telomere length.

The disclosed hTS cells exhibit FGF-dependent gene switching/knockdown of Oct4 and FGFR2, supporting regulation of trophoblast-related gene expression. The patent describes multilineage differentiation capacity of hTS cells, including differentiation into pancreatic islet-like cells and insulin secretion behavior, and differentiation into neural lineages including dopaminergic neuron features.

The disclosed hTS cells are positioned as a gene/cell-therapy platform for therapeutic use. The patent describes in vivo behavior including mouse chimera/teratoma-like behavior and transplantation in a Parkinsonian model with evidence of dopaminergic marker changes, and it also frames therapeutic compositions and an in vitro screening method for therapeutics that modulate hTS differentiation/activity.

Claims Coverage

The partial claim set includes two independent claims, focused on (i) a diabetes treatment method using hTS cells expressing SSEA-1, SSEA-3, and SSEA-4 and (ii) a therapeutic composition that includes those hTS cells plus a buffer and an additional therapeutic compound. Across the dependents shown, the inventive features mainly refine the diabetes subtype, administration/formulation, and the characterization/identity of accompanying compounds (including immunosuppressive or immunosupportive agents).

The independent claims center on using isolated human trophoblast stem cells expressing SSEA-1, SSEA-3, and SSEA-4 either as a direct diabetes-treatment agent or as the cellular component of a therapeutic composition combined with a buffer solution and an additional therapeutic compound. The dependent claim refinements in the provided set further specify diabetes subtype (type 1), administration route (e.g., transplantation), and the functional category or formulation elements of accompanying components.

Stated Advantages

Documented Applications