Mesenchymal stem cells targeting PI3K/AKT pathway in leukemic model

Abstract

Mesenchymal stem cells have therapeutic properties that are related to their potentials for trans-differentiation, immunomodulation, anti-inflammatory, inhibitory effect on tumor proliferation, and induction of apoptosis. This study was performed to analyze the role of mesenchymal stem cells as an alternative for cellular signaling growth factors involved in the pathogenesis of leukemogenesis in rats. Treatment of rats with 7,12-dimethyl benz [a] anthracene induced leukemogenesis appeared as a significant decrease in hematological parameters with concomitant significant increase in bone marrow oxidative and inflammatory indices (transforming growth factor beta and interleukin-6) in comparison with normal groups. On the contrary, Western immunoblotting showed a significant increase in the signaling growth factors: PI3K, AKT, mTOR proteins and a significant decrease in PTEN in 7,12-dimethyl benz [a] anthracene-treated group. In addition, a significant increase in the transcript levels of B cell lymphoma-2 protein gene in the 7,12-dimethyl benz [a] anthracene group, while that of C-X-C motif chemokine receptor-4 and B cell lymphoma-2 protein associated x-protein were significantly downregulated compared to controls. Meanwhile, therapeutic mesenchymal stem cells treatment predict a significant improvement versus 7,12-dimethyl benz [a] anthracene group through the modulation of growth factors that confront bone marrow dysplasia. In the same direction treatment of 7,12-dimethyl benz [a] anthracene group with mesenchymal stem cells, it induced apoptosis and increased the homing efficacy to bone marrow. In conclusion, mesenchymal stem cells improve hematopoiesis and alleviate inflammation, and modulated PI3K/AKT signaling pathway contributed to experimental leukemogenesis.

The potential ameliorative effect of Bone marrow Derived Mesenchymal Stem Cells on Cyclophosphamide Injured Lung in Adult Female Albino Rats

“…The close correlation between mesenchymal stem cells treatment and downregulation of a PI3K/AKT pathway raises the suggestion of their anti-tumorigenic effect, these suggestions were supported by the work of authors who explained the anti-tumorigenic role of MScs in acute myeloid leukaemia (AML) animal model by their inhibitory effect on PI3K/AKT/mTOR pathway plays, that plays a vital role in the cell survival, proliferation, migration, cell cycle and apoptosis. Furthermore MScs might exert a potential improvement in microenvironment, cytokines in addition to improving proliferation by downregulation of (X-linked inhibitor of apoptosis protein),thus up-regulation BCL2 and P53 in the present study after MSCs treatment further add to the potential ameliorative effect in pulmonary parenchyma [33] .…”

Mesenchymal stem cells promote human melanocytes proliferation and resistance to apoptosis through PTEN pathway in vitiligo

“…MSCs have been shown to produce and release growth factors, exosomes, and cytokines that affect cells in their vicinity, which are induced into different developmental pathways [30]. It has been reported that MSC-derived PI3K/AKT signaling, and lead to protection against oxidative stress-triggered cell death [32]. Therefore, we reasoned that MSCs might target some specific genes or signaling networks to function as a potential therapeutic approach for vitiligo.…”

Antioxidant mechanisms of mesenchymal stem cells and their therapeutic potential in vitiligo

“…Melanocytes extracted from human foreskin tissue (passed on to the second or third generation) transfected with a PTEN expression plasmid and co-cultured with human BMMSCs resulted in the BMMSCs down-regulating their PTEN expression ( Zhu et al, 2020 ). In addition, BMMSCs can reduce PTEN expression in the presence of oxidative stress in vitro in a 7,12-dimethylbenz [a]anthracene (DMBA)-induced leukemia cell model and a melanocytic vitiligo model, where they increased AKT phosphorylation and prevented oxidative stress-triggered cell death ( Ahmed et al, 2019 ; Zhu et al, 2020 ). Phosphorylation inactivates PTEN ( Vazquez et al, 2001 ; Das et al, 2003 ).…”