BMP-2 Induced Signaling Pathways and Phenotypes: Comparisons Between Senescent and Non-senescent Bone Marrow Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Jae Hwan Cho ◽  
Jae Hyup Lee ◽  
Kyung Mee Lee ◽  
Choon-Ki Lee ◽  
Dong-Myung Shin
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Bone marrow mesenchymal stem cells and their derived exosomes resolve doxorubicin-induced chemobrain: critical role of their miRNA cargo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marwa O. El-Derany ◽  
Mohamed H. Noureldein
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Hedgehog Signaling ◽  
Critical Role ◽  
Receptor Expression ◽  
Therapeutic Effects ◽  
Marrow Mesenchymal Stem Cells ◽  
Hippocampal Neurodegeneration

Abstract Background Doxorubicin (DOX), a widely used chemotherapeutic agent, can cause neurodegeneration in the brain, which leads to a condition known as chemobrain. In fact, chemobrain is a deteriorating condition which adversely affects the lives of cancer survivors. This study aimed to examine the potential therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) and their derived exosomes (BMSCs-Exo) in DOX-induced chemobrain in rat models. Methods Chemobrain was induced by exposing rats to DOX (2 mg/kg, i.p) once weekly for 4 consecutive weeks. After 48 h of the last DOX dose, a subset of rats was supplied with either an intravenous injection of BMSCs (1 × 106) or a single dose of 150 μg of BMSCs-Exo. Behavioral tests were conducted 7 days post injection. Rats were sacrificed after 14 days from BMSCs or BMSCs-Exo injection. Results BMSCs and BMSCs-Exo successfully restored DOX-induced cognitive and behavioral distortion. These actions were mediated via decreasing hippocampal neurodegeneration and neural demyelination through upregulating neural myelination factors (myelin%, Olig2, Opalin expression), neurotropic growth factors (BDNF, FGF-2), synaptic factors (synaptophysin), and fractalkine receptor expression (Cx3cr1). Halting neurodegeneration in DOX-induced chemobrain was achieved through epigenetic induction of key factors in Wnt/β-catenin and hedgehog signaling pathways mediated primarily by the most abundant secreted exosomal miRNAs (miR-21-5p, miR-125b-5p, miR-199a-3p, miR-24-3p, let-7a-5p). Moreover, BMSCs and BMSCs-Exo significantly abrogate the inflammatory state (IL-6, TNF-α), apoptotic state (BAX/Bcl2), astrocyte, and microglia activation (GFAP, IBA-1) in DOX-induced chemobrain with a significant increase in the antioxidant mediators (GSH, GPx, SOD activity). Conclusions BMSCs and their derived exosomes offer neuroprotection against DOX-induced chemobrain via genetic and epigenetic abrogation of hippocampal neurodegeneration through modulating Wnt/β-catenin and hedgehog signaling pathways and through reducing inflammatory, apoptotic, and oxidative stress state. Graphical abstract Proposed mechanisms of the protective effects of bone marrow stem cells (BMSCs) and their exosomes (BMSCs-Exo) in doxorubicin (DOX)-induced chemobrain. Blue arrows: induce. Red arrows: inhibit.

scholarly journals Aromatic Amino Acid Activation of Signaling Pathways in Bone Marrow Mesenchymal Stem Cells Depends on Oxygen Tension

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e91108 ◽  
Author(s):  
Mona El Refaey ◽  
Qing Zhong ◽  
William D. Hill ◽  
Xing-Ming Shi ◽  
Mark W. Hamrick ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Amino Acid ◽  
Signaling Pathways ◽  
Oxygen Tension ◽  
Aromatic Amino Acid ◽  
Acid Activation ◽  
Amino Acid Activation ◽  
Marrow Mesenchymal Stem Cells
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