Epigenetic mechanisms such as histone methylation are considered as one of the most important mediators that control stem cell behaviors such as proliferation, senescence and differentiation. G9a, a histone methyltransferase, has recently generated intense attention as potential target for controlling many diseases such as cancers. The aim of the present study was to evaluate the effect of administration of A366, a G9a inhibitor, on proliferative and differentiation potential of bone marrow-derived mesenchymal stem cells (BM-MSCs). We inhibited G9a using intraperitoneally administration of A366, and we evaluated BM-MSC proliferation and differentiation behaviors . Colony formation assay of BM-MSCs at primary culture showed that administration of A366 reduced the colony forming capacity of BM-MSCs. Moreover, PDT of BM-MSC isolated from A366-treated rats was higher than control, especially in the early passages. BM-MSC isolated from A366-treated rats showed higher adipogenic potential compared to the control at the early passages as determined by gene expression and Oil Red staining. Whereas, osteogenic potential of BM-MSC isolated from A366-treated rats was lower than control, especially at early passages. Our results suggest that the epigenetic modifier such as A366, which seems to be a therapeutic approach for controlling diseases such as cancer, might also influence the proliferation and differentiation capacity of MSCs both and . Moreover, epigenetic modifying chemicals seem to be a strategy to manipulate MSC expansion capacity and differentiation propensity, as well as to efficiently involvement of MSCs in tissue homeostasis, cell-based therapy and tissue engineering.
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http://dx.doi.org/10.17179/excli2019-1234 | DOI Listing |
EXCLI J
June 2019
Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Epigenetic mechanisms such as histone methylation are considered as one of the most important mediators that control stem cell behaviors such as proliferation, senescence and differentiation. G9a, a histone methyltransferase, has recently generated intense attention as potential target for controlling many diseases such as cancers. The aim of the present study was to evaluate the effect of administration of A366, a G9a inhibitor, on proliferative and differentiation potential of bone marrow-derived mesenchymal stem cells (BM-MSCs).
View Article and Find Full Text PDFOncotarget
April 2016
Investigative Clinical Oncology, Fondazione del Piemonte per l'Oncologia-Candiolo Cancer Institute (IRCCs), Candiolo, Italy.
We recently found that trastuzumab benefit may be lower in a small subset of early breast cancer (BC) patients (pts) with tumors expressing high levels of both hormonal receptors (HRs), i.e. triple positive (TP).
View Article and Find Full Text PDFValue Health
November 2014
Pharmerit International, Rotterdam, The Netherlands.
Ned Tijdschr Geneeskd
February 2010
Integraal Kankercentrum Oost, Nijmegen, The Netherlands.
Objective: To determine the current situation regarding the epidemic of clear cell adenocarcinoma of the vagina and the uterine cervix (CCAC) in relation to the exposure in utero to diethylstilbestrol (DES).
Design: Descriptive.
Methods: Patients with CCAC of the uterine cervix or vagina born after 1946 and diagnosed in the period 1969-2005, were identified through the Nationwide network and registry of histo- and cytopathology in the Netherlands and from 2003 onwards through the Netherlands Cancer Registry.
Environ Health Perspect
August 1998
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