Leveraging chorionic villus biopsies for the derivation of patient-specific trophoblast stem cells

Abstract

Human trophoblast stem (TS) cells are an informative in vitro model for the generation and testing of biologically meaningful hypotheses. The goal of this project was to derive patient-specific TS cell lines from clinically available chorionic villus sampling (CVS) biopsies. Cell outgrowths were captured from human CVS tissue specimens cultured in modified human TS cell medium. Cell colonies emerged early during the culture and cell lines were established and passaged for several generations. Karyotypes of the newly established CVS-derived trophoblast stem (TSCV) cell lines were determined and compared to initial genetic diagnoses from freshly isolated chorionic villi. Phenotypes of TSCV cells in the stem state and following differentiation were compared to cytotrophoblast-derived TS (TSCT) cells. TSCV and TSCT cells uniformly exhibited similarities in the stem state and following differentiation into syncytiotrophoblast. These shared features included morphology and gene expression. TSCV cell differentiation into extravillous trophoblast cells exhibited cell line dependent phenotypes. CVS tissue specimens provide a valuable source for TS cell derivation. They expand the genetic diversity of available TS cells and are associated with defined clinical outcomes. TSCV cell lines provide a new set of experimental tools for investigating trophoblast cell lineage development.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by F32HD096809 (KMV); The Lalor Foundation (AM); HD091773 and AI154535 (MDP); HD020676, HD099638, HD105734, and the Sosland Foundation (MJS).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

All human tissue specimens used for research purposes were collected following informed written consent, deidentified, and approved by institutional review boards at both Cedars-Sinai Medical Center and at the University of Kansas Medical Center.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors.

留言 (0)

沒有登入
gif