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Absolute Quantitation of Inositol Pyrophosphates by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry
09:22

Absolute Quantitation of Inositol Pyrophosphates by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry

Published on: August 13, 2021

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Inositol pyrophosphates mediate the effects of aging on bone marrow mesenchymal stem cells by inhibiting Akt

Zheng Zhang, Chuanxu Zhao, Bing Liu

    Stem Cell Research & Therapy
    |March 28, 2014
    PubMed
    Abstract

    Insights

    Inhibiting inositol phosphates 6 kinase (IP6Ks) with TNP improves aged bone marrow-derived mesenchymal stem cells (BM-MSCs) function. This treatment enhances cell survival and paracrine signaling, crucial for myocardial infarction therapy.

    Area of Science:

    • Stem Cell Biology
    • Regenerative Medicine
    • Molecular Biology

    Background:

    • Bone marrow-derived mesenchymal stem cells (BM-MSCs) are promising for myocardial infarction (MI) therapy.
    • Aging impairs MSC viability and function, limiting therapeutic efficacy.
    • Mechanisms behind aged MSC dysfunction, particularly under stress, require clarification.

    Purpose of the Study:

    • To investigate the role of inositol phosphates 6 kinase (IP6Ks) inhibition in aged BM-MSC therapeutic potential.
    • To elucidate the underlying molecular mechanisms of IP6Ks' impact on aged MSCs under hypoxic injury.

    Main Methods:

    • BM-MSCs were isolated from young and aged mice.
    • Cells were subjected to hypoxia and serum deprivation (H/SD) with or without an IP6Ks inhibitor (TNP).
    • Apoptosis, protein expression (Western blot), and paracrine factor secretion (RT-PCR, ELISA) were analyzed.

    Main Results:

    • Aged BM-MSCs showed increased inositol pyrophosphate 7 (IP7) and apoptosis, with reduced Akt phosphorylation compared to young MSCs.
    • TNP treatment inhibited IP7 production, enhanced Akt phosphorylation, and reduced apoptosis in aged MSCs.
    • TNP administration improved the expression of angiogenic factors and enhanced the paracrine efficiency of aged BM-MSCs.

    Conclusions:

    • IP6Ks and IP7 are critical in age-related vulnerability of BM-MSCs to hypoxic injury and impaired function.
    • Inhibition of IP6Ks restores aged BM-MSC viability and paracrine function via improved Akt activation.
    • Targeting IP6Ks offers a potential strategy to enhance MSC-based therapies for myocardial infarction.

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