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[Cell-free DNA fragments increase transcription in human mesenchymal stem cells, activate TLR-dependent signal

S V Kostiuk, E M Malinovskaia, A V Ermakov

    Biomeditsinskaia Khimiia
    |January 29, 2013
    PubMed

    Insights

    Cell-free DNA (cfDNA) fragments influence human mesenchymal stem cells (MSCs) by activating TLR9 and MyD88 signaling pathways. This process also lowers apoptosis, impacting MSC functional activity in regenerative medicine.

    Area of Science:

    • Stem cell biology
    • Molecular biology
    • Immunology

    Background:

    • Human mesenchymal stem cells (MSCs) are crucial for regenerative medicine.
    • The role of signaling pathways in regulating stem cell (SC) function in vivo is not fully understood.
    • Increased cell death in damaged tissues leads to accumulation of cell-free DNA (cfDNA) in circulation.

    Purpose of the Study:

    • To investigate the effects of cfDNA fragments on the functional activity of adipose-derived MSCs.
    • To elucidate the specific signaling pathways involved in MSC response to cfDNA.
    • To determine if cfDNA influences MSC apoptosis.

    Main Methods:

    • In vitro exposure of adipose-derived MSCs to cfDNA fragments.
    • Analysis of transcription levels (total RNA, rRNA).
    • Assessment of TLR9 and MyD88 expression.
    • Measurement of caspase activity.

    Main Results:

    • cfDNA fragments increased transcription levels in MSCs.
    • GC-rich cfDNA activated the TLR9-dependent pathway, up-regulating TLR9 and MyD88 expression.
    • AT-rich cfDNA increased MyD88 expression, suggesting alternative receptor activation.
    • cfDNA fragments reduced caspase activity, indicating decreased apoptosis.

    Conclusions:

    • cfDNA significantly influences MSC functional activity.
    • TLR9 and MyD88-dependent signaling pathways are key mediators of MSC response to cfDNA.
    • cfDNA can modulate MSC apoptosis levels.

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