The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Aug. 16, 2022

Filed:

Mar. 23, 2018
Applicant:

Cedars-sinai Medical Center, Los Angeles, CA (US);

Inventors:

Clive N. Svendsen, Pacific Palisades, CA (US);

Beth Y. Karlan, Los Angeles, CA (US);

Nur Yucer, Los Angeles, CA (US);

Marie Holzapfel, Los Angeles, CA (US);

Tilly Jenkins Vogel, Los Angeles, CA (US);

Assignee:

Cedars-Sinai Medical Center, Los Angeles, CA (US);

Attorney:
Primary Examiner:
Int. Cl.
CPC ...
C12N 5/071 (2010.01); A61K 35/48 (2015.01);
U.S. Cl.
CPC ...
C12N 5/0682 (2013.01); A61K 35/48 (2013.01); C12N 2501/155 (2013.01); C12N 2501/16 (2013.01); C12N 2501/392 (2013.01); C12N 2501/415 (2013.01); C12N 2501/999 (2013.01); C12N 2506/45 (2013.01); C12N 2513/00 (2013.01);
Abstract

The fallopian tube epithelium (FTE) has been recognized as a site of origin of high-grade serous ovarian cancer (HGSC). However, absence of relevant in vitro human models that can recapitulate tissue-specific architecture has hindered understanding of FTE transformation and initiation of HGSC. Here, induced pluripotent stem cells (iPSCs) were used to establish a novel 3-dimensional (3D) human FTE organoid in vitro model containing the relevant cell types of the human fallopian tube as well as a luminal architecture that closely reflects the organization of fallopian tissues in vivo. Modulation of Wnt and nodal/activin signaling pathways provided iPSC differentiation into Müllerian cells and subsequent use of pro-Müllerian growth factors promoted FTE precursors. The expression of Müllerian markers verified correct cellular differentiation. An innovative 3D growth platform, which enabled the FTE organoid to self-organize into a convoluted luminal structure, permitted final differentiation to a FTE lineage. This powerful human-derived FTE organoid model can be used to study the earliest stages of HGSC development and to identify novel and specific biomarkers of early fallopian tube epithelial cell transformation.


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