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Mesenchymal stem cells targeting PI3K/AKT pathway in leukemic model

Esraa S A Ahmed1, Neamat H Ahmed1, Amina M Medhat2

  • 11 National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|April 26, 2019
PubMed

Insights

Mesenchymal stem cells (MSCs) show promise in treating leukemogenesis by improving blood cell production and reducing inflammation. MSCs modulate key signaling pathways like PI3K/AKT, offering a potential alternative to growth factors in cancer therapy.

Area of Science:

  • Hematology
  • Oncology
  • Stem Cell Biology

Background:

  • Leukemogenesis involves dysregulated cellular signaling and inflammation.
  • Mesenchymal stem cells (MSCs) possess immunomodulatory and anti-inflammatory properties.
  • The role of MSCs in modulating signaling pathways in leukemogenesis is not fully understood.

Purpose of the Study:

  • To investigate MSCs as an alternative to cellular signaling growth factors in rat leukemogenesis.
  • To analyze the impact of MSCs on PI3K/AKT/mTOR signaling pathway in leukemogenesis.
  • To evaluate MSCs' therapeutic potential in improving hematopoiesis and reducing inflammation.

Main Methods:

  • Induction of leukemogenesis in rats using 7,12-dimethyl benz [a] anthracene (DMBA).
  • Assessment of hematological parameters, bone marrow oxidative and inflammatory indices (TGF-β, IL-6).
  • Western immunoblotting to analyze PI3K, AKT, mTOR, and PTEN protein levels.
  • Gene expression analysis for BCL-2, CXCR4, and BAX.
  • Evaluation of MSCs' therapeutic effects on hematopoiesis, inflammation, apoptosis, and bone marrow homing.

Main Results:

  • DMBA treatment significantly decreased hematological parameters and increased bone marrow inflammation (TGF-β, IL-6).
  • DMBA-induced leukemogenesis showed increased PI3K, AKT, mTOR, and BCL-2, with decreased PTEN, CXCR4, and BAX.
  • MSC treatment significantly improved hematological parameters and reduced inflammatory markers.
  • MSCs modulated the PI3K/AKT signaling pathway, induced apoptosis, and enhanced bone marrow homing.

Conclusions:

  • MSCs effectively improve hematopoiesis and alleviate inflammation in experimental leukemogenesis.
  • MSC therapy modulates the PI3K/AKT signaling pathway, offering a therapeutic strategy for leukemogenesis.
  • MSCs represent a promising alternative for cellular signaling growth factors in managing leukemogenesis.
Keywords:
B cell lymphoma-2 proteinB cell lymphoma-2 protein–associated x-proteinC-X-C motif chemokine receptor-4LeukemogenesisPI3Kmesenchymal stem cells

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