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Published on: August 23, 2024
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.
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.
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