Journal article
Placental mesenchymal stem cells of fetal origin deposit epigenetic alterations during long-term culture under serum-free condition
Expert opinion on biological therapy, Vol.15(2), pp.163-180
02/01/2015
DOI: 10.1517/14712598.2015.960837
PMID: 25231124
Abstract
Objective: Fetal placental mesenchymal stem cells (fPMSCs) have shown promising cell therapy potentials. However, their genetic and epigenetic stability during in vitro propagation has not been well studied. We thus interrogated the methylation alterations and tumorigenicity of fPMSCs after in vitro expansion using serum-free medium.
Research design and methods: The properties of fPMSCs cultured in a serum-free medium at passage 3 and passage 8 were ascertained by determining their MSC markers, proliferative capacity, chromosomal stability, activity of global DNA methyltransferases and methylation profile. Their potential of malignant transformation was also evaluated in a severe combined immunodeficiency (SCID) murine model.
Results: The fPMSCs could maintain their MSC characteristics but quickly reached a senescent state of proliferation during in vitro expansion. 246 genes with differential DNA methylation of promoters were identified, along with a significantly downregulated global DNA methyltransferase activity. The genes associated with aging and tumorigenesis had a significantly demethylated tendency over in vitro propagation. However, the deposition of epigenetic alterations did not translate into malignant transformation in SCID mice.
Conclusion: The fPMSCs cultured in serum-free medium have a tendency to deposit methylation modifications over in vitro expansion, therefore the detection of genetic and/or epigenetic alterations is necessary for fPMSCs before they are employed for clinical uses.
Details
- Title: Subtitle
- Placental mesenchymal stem cells of fetal origin deposit epigenetic alterations during long-term culture under serum-free condition
- Creators
- Yongzhao Zhu - Ningxia UniversityXumei Song - Ningxia Medical UniversityJian Wang - Ningxia Medical UniversityYukui Li - Ningxia Medical UniversityYinxue Yang - Ningxia Medical UniversityTingting Yang - Ningxia Medical UniversityHaibin Ma - Ningxia Medical UniversityLibin Wang - Ningxia Medical UniversityGuangyi Zhang - Ningxia Medical UniversityWilliam C Cho - Queen Elizabeth Hospital, Department of Clinical OncologyXiaoming Liu - Ningxia UniversityJun Wei - Ningxia Medical University
- Resource Type
- Journal article
- Publication Details
- Expert opinion on biological therapy, Vol.15(2), pp.163-180
- Publisher
- Informa Healthcare
- DOI
- 10.1517/14712598.2015.960837
- PMID
- 25231124
- ISSN
- 1471-2598
- eISSN
- 1744-7682
- Language
- English
- Date published
- 02/01/2015
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984288579402771
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