scholarly journals Exosomes derived from embryonic stem cells inhibit doxorubicin and inflammation-induced pyroptosis in muscle cells

2018 ◽  
Vol 96 (3) ◽  
pp. 304-307 ◽  
Author(s):  
Zahra Tavakoli Dargani ◽  
Reetu Singla ◽  
Taylor Johnson ◽  
Rakesh Kukreja ◽  
Dinender K. Singla
Keyword(s):  
Inflammatory Cytokine ◽  
In Vitro Model ◽  
Embryonic Stem ◽  
Mouse Embryonic Fibroblast ◽  
Caspase 1 ◽  
Key Players ◽  
Vitro Model ◽  
Embryonic Fibroblast ◽  
Muscle Toxicity

Doxorubicin (Dox) is an effective anticancer drug. Unfortunately, it causes cardiac and muscle toxicity due to increased oxidative stress and inflammation; however, it remains unknown whether Dox induces “pyroptosis” — an inflammation-mediated cell death. We investigated whether Dox induces pyroptosis in mouse soleus muscle (Sol 8) cells in vitro and to show the protective effect of embryonic stem cell exosomes (ES-exos) on pyroptosis. Dox and inflammation-induced in vitro model was generated. Pyroptosis was confirmed using immunohistochemistry (with putative markers caspase-1, IL-1β, and pro-inflammatory cytokine IL-18) and Western blotting of caspase-1 and IL-1β. The results show significant increase in the expression of caspase-1, IL-1β, and IL-18 following treatment with Dox, which was inhibited by ES-exos but not mouse embryonic fibroblast exosomes. Moreover, GW4869 compound inhibited functional activity of ES-exos, suggesting these vesicles are key players in the inhibition of pyroptosis. These results suggest that Dox induces inflammatory pyroptosis in Sol 8 cells, which is attenuated by ES-exos in vitro.

scholarly journals Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Muscle Toxicity through Counteracting Pyroptosis

2020 ◽  
Vol 13 (12) ◽  
pp. 450
Author(s):  
Fatima Bianca A. Dessouki ◽  
Rakesh C. Kukreja ◽  
Dinender K. Singla
Keyword(s):  
Muscle Function ◽  
Muscular Atrophy ◽  
Embryonic Stem ◽  
Mouse Embryonic Fibroblast ◽  
Negative Control ◽  
M1 Macrophages ◽  
Tnf Α ◽  
Embryonic Fibroblast ◽  
Muscle Toxicity

Doxorubicin (Dox)-induced muscle toxicity (DIMT) is a common occurrence in cancer patients; however, the cause of its development and progression is not established. We tested whether inflammation-triggered cell death, “pyroptosis” plays a role in DIMT. We also examined the potential role of exosomes derived from embryonic stem cells (ES-Exos) in attenuating DIMT. C57BL/6J mice (10 ± 2 wks age) underwent the following treatments: Control (saline), Dox, Dox+ES-Exos, and Dox+MEF-Exos (mouse-embryonic fibroblast-derived exosomes, negative control). Our results demonstrated that Dox significantly reduced muscle function in mice, which was associated with a significant increase in NLRP3 inflammasome and initiation marker TLR4 as compared with controls. Pyroptosis activator, ASC, was significantly increased compared to controls with an upregulation of specific markers (caspase-1, IL-1β, and IL-18). Treatment with ES-Exos but not MEF-Exos showed a significant reduction in inflammasome and pyroptosis along with improved muscle function. Additionally, we detected a significant increase in pro-inflammatory cytokines (TNF-α and IL-6) and inflammatory M1 macrophages in Dox-treated animals. Treatment with ES-Exos decreased M1 macrophages and upregulated anti-inflammatory M2 macrophages. Furthermore, ES-Exos showed a significant reduction in muscular atrophy and fibrosis. In conclusion, these results suggest that DIMT is mediated through inflammation and pyroptosis, which is attenuated following treatment with ES-Exos.

scholarly journals Hematopoietic Differentiation of Embryonic Stem Cells: An In Vitro Model to Study Gene Regulation during Megakaryocytopoiesis

Stem Cells ◽  
1996 ◽  
Vol 14 (S1) ◽  
pp. 194-199 ◽  
Author(s):  
Georges Uzan ◽  
Marie‐Hélène Prandini ◽  
Jean‐Philippe Rosa ◽  
Rolande Berthier
Keyword(s):  
Stem Cells ◽  
Gene Regulation ◽  
Embryonic Stem Cells ◽  
In Vitro Model ◽  
Embryonic Stem ◽  
Hematopoietic Differentiation ◽  
Vitro Model ◽  
Study Gene Regulation

scholarly journals An In Vitro Model of Human Dopaminergic Neurons Derived from Embryonic Stem Cells: MPP+ Toxicity and GDNF Neuroprotection

2006 ◽  
Vol 31 (12) ◽  
pp. 2708-2715 ◽  
Author(s):  
Xianmin Zeng ◽  
Jia Chen ◽  
Xiaolin Deng ◽  
Ying Liu ◽  
Mahendra S Rao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Dopaminergic Neurons ◽  
In Vitro Model ◽  
Embryonic Stem ◽  
Vitro Model

scholarly journals Sophorolipid treatment decreases inflammatory cytokine expression in an in vitro model of experimental sepsis

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Cathy M Mueller ◽  
Yin‐yao Lin ◽  
Domenico Viterbo ◽  
Joelle Pierre ◽  
Shirley A Murray ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
In Vitro Model ◽  
Cytokine Expression ◽  
Experimental Sepsis ◽  
Vitro Model
Sign in / Sign up

Export Citation Format

Share Document