TY - JOUR
T1 - The MicroRNA-371 Family as Plasma Biomarkers for Monitoring Undifferentiated and Potentially Malignant Human Pluripotent Stem Cells in Teratoma Assays
AU - Salvatori, Daniela C F
AU - Dorssers, Lambert C J
AU - Gillis, Ad J M
AU - Perretta, Gemma
AU - van Agthoven, Ton
AU - Gomes Fernandes, Maria
AU - Stoop, Hans
AU - Prins, Jan-Bas
AU - Oosterhuis, J Wolter
AU - Mummery, Christine
AU - Looijenga, Leendert H J
N1 - Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2018/12/11
Y1 - 2018/12/11
N2 - Predicting developmental potency and risk of posttransplantation tumor formation by human pluripotent stem cells (hPSCs) and their derivatives largely rely on classical histological analysis of teratomas. Here, we investigated whether an assay based on microRNAs (miRNA) in blood plasma is able to detect potentially malignant elements. Several hPSCs and human malignant germ cell tumor (hGCT) lines were investigated in vitro and in vivo after mouse xenografting. The multiple conventional hPSC lines generated mature teratomas, while xenografts from induced hPSCs (hiPSCs) with reactivated reprogramming transgenes and hGCT lines contained undifferentiated and potentially malignant components. The presence of these elements was reflected in the mRNA and miRNA profiles of the xenografts with OCT3/4 mRNA and the miR-371 and miR-302 families readily detectable. miR-371 family members were also identified in mouse plasma faithfully reporting undifferentiated elements in the xenografts. This study demonstrated that undifferentiated and potentially malignant cells could be detected in vivo.
AB - Predicting developmental potency and risk of posttransplantation tumor formation by human pluripotent stem cells (hPSCs) and their derivatives largely rely on classical histological analysis of teratomas. Here, we investigated whether an assay based on microRNAs (miRNA) in blood plasma is able to detect potentially malignant elements. Several hPSCs and human malignant germ cell tumor (hGCT) lines were investigated in vitro and in vivo after mouse xenografting. The multiple conventional hPSC lines generated mature teratomas, while xenografts from induced hPSCs (hiPSCs) with reactivated reprogramming transgenes and hGCT lines contained undifferentiated and potentially malignant components. The presence of these elements was reflected in the mRNA and miRNA profiles of the xenografts with OCT3/4 mRNA and the miR-371 and miR-302 families readily detectable. miR-371 family members were also identified in mouse plasma faithfully reporting undifferentiated elements in the xenografts. This study demonstrated that undifferentiated and potentially malignant cells could be detected in vivo.
KW - Animals
KW - Biological Assay/methods
KW - Biomarkers, Tumor/blood
KW - Cell Differentiation/genetics
KW - Cell Line
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Mice
KW - MicroRNAs/blood
KW - Neoplasms, Germ Cell and Embryonal/genetics
KW - Pluripotent Stem Cells/metabolism
KW - Principal Component Analysis
KW - RNA, Messenger/genetics
KW - Teratoma/blood
KW - Time Factors
KW - Xenograft Model Antitumor Assays
UR - http://www.scopus.com/inward/record.url?scp=85058601893&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2018.11.002
DO - 10.1016/j.stemcr.2018.11.002
M3 - Article
C2 - 30503260
SN - 2213-6711
VL - 11
SP - 1493
EP - 1505
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 6
ER -