The MicroRNA-371 Family as Plasma Biomarkers for Monitoring Undifferentiated and Potentially Malignant Human Pluripotent Stem Cells in Teratoma Assays

Autor: Daniela C.F. Salvatori, Lambert C.J. Dorssers, Ad J.M. Gillis, Gemma Perretta, Ton van Agthoven, Maria Gomes Fernandes, Hans Stoop, Jan-Bas Prins, J. Wolter Oosterhuis, Christine Mummery, Leendert H.J. Looijenga
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Stem Cell Reports, Vol 11, Iss 6, Pp 1493-1505 (2018)
Druh dokumentu: article
ISSN: 2213-6711
DOI: 10.1016/j.stemcr.2018.11.002
Popis: Summary: 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. : Salvatori et al. showed histological, mRNA, microRNA similarities between human germ cell tumors and xenografts derived from human pluripotent stem cells (hPSCs). miR-371, -302, and C19MC families were present in the blood plasma of mice after injection of hPSCs (teratoma assay) and were indicative of undifferentiated and potentially malignant cells in the growing xenograft. Keywords: teratoma, human pluripotent stem cells, malignant elements, embryonal carcinoma, human germ cell tumors, microRNA
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