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Isolation and Enrichment of Human Adipose-derived Stromal Cells for Enhanced Osteogenesis
Published on: January 12, 2015
Increased DNA damage of adipose tissue-derived mesenchymal stem cells under inflammatory conditions
Zoltán G Páhi1,2, Diána Szűcs3,4,5, Vanda Miklós1,6
1Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Genome Integrity and DNA Repair Core Group, University of Szeged, Szeged, Hungary.
Abstract:
Cells have evolved various DNA repair mechanisms to prevent DNA damage from building up. Malfunctions during DNA repair can influence cellular homeostasis because they can bring on genomic instability through the improper recognition of DNA damage or dysregulation of the repair process. Maintaining proper DNA repair is also essential for stem cells (SCs), as they provide a differentiated cell population to the living organism. SCs are regularly used in personalized stem cell therapy. Patients must be treated with specific activators to produce these SCs effectively. This report investigated the impact of treating mesenchymal stem cells (MSC) with lipopolysaccharide, tumor necrosis factor, interferon-gamma, polyinosinic acid, interleukin 1 beta, while monitoring their transcription-related response using next-generation sequencing. RNA sequencing revealed robust gene expression changes, including those of specific genes encoding proteins implicated in DNA damage response. Stem cells can effectively repair specific DNA damages; moreover, they fail to undergo senescence or cell death when genetic lesions accumulate. Here, we draw attention to an elevated DNA repair activation following MSC induction, which may be the main reason for the ineffective stem cell transplantation and may also contribute to the genetic drift that can initiate tumor formation.
Insights
Mesenchymal stem cells (MSCs) show increased DNA repair activation after treatment with specific factors. This heightened repair may hinder effective stem cell transplantation and contribute to tumor formation.
Area of Science:
- Molecular Biology
- Cell Biology
- Genomics
Background:
- DNA repair is crucial for cellular homeostasis and genomic stability.
- Stem cells (SCs) rely on DNA repair for their function and therapeutic applications.
- Mesenchymal stem cells (MSCs) are vital for regenerative medicine and require effective DNA repair.
Purpose of the Study:
- To investigate the impact of specific immune factors on DNA repair mechanisms in MSCs.
- To analyze the transcriptional response of MSCs to various activating agents.
- To understand how MSC induction affects DNA damage response pathways.
Main Methods:
- Treatment of MSCs with lipopolysaccharide, tumor necrosis factor, interferon-gamma, polyinosinic acid, and interleukin 1 beta.
- Monitoring cellular response using next-generation sequencing (NGS).
- RNA sequencing to analyze gene expression changes, particularly in DNA damage response genes.
Main Results:
- RNA sequencing revealed significant gene expression alterations in treated MSCs.
- Elevated activation of DNA repair pathways was observed following MSC induction.
- MSCs demonstrated a reduced capacity for senescence or apoptosis despite accumulating genetic lesions.
Conclusions:
- Enhanced DNA repair activation in induced MSCs may compromise stem cell transplantation efficacy.
- The dysregulation of DNA repair in MSCs could promote genetic instability and tumor initiation.
- Further research is needed to optimize MSC activation protocols for therapeutic use.
